Opdivo Drug Information

Advanced Renal Cell Carcinoma Previously Treated Renal Cell Carcinoma - OPDIVO QVANTIG The efficacy of OPDIVO QVANTIG was evaluated in CHECKMATE-67T (NCT04810078), a multicenter, randomized, open-label study in patients with advanced or metastatic clear cell renal cell carcinoma. Patients 18 years of age or older with histologically confirmed advanced or metastatic renal cell carcinoma with a clear cell component, including those with sarcomatoid features, and who received no more than 2 prior systemic treatment regimens were randomized to receive OPDIVO QVANTIG (containing 1,200 mg of nivolumab and 20,000 units of hyaluronidase) every 4 weeks subcutaneously, or nivolumab 3 mg/kg every 2 weeks intravenously. Patients with untreated, symptomatic central nervous system (CNS) metastases; leptomeningeal metastases; concurrent malignancies requiring treatment or history of prior malignancy within the previous 2 years; active, known, or suspected autoimmune disease; or who received prior treatment with a checkpoint inhibitor were excluded from the study.

Patients with asymptomatic, stable CNS metastases that did not require immediate treatment were eligible if there was no evidence of progression within 28 days prior to the first dose of study drug administration. Stratification factors for randomization were weight (<80 kg vs ≥80 kg) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification (favorable vs intermediate, vs poor risk). The primary objective was to assess the nivolumab exposure of subcutaneous administration of OPDIVO QVANTIG as compared to the intravenous administration of nivolumab.

The secondary objective of the study was to evaluate overall response rate (ORR) by blinded independent central review (BICR). A total of 495 patients were randomized to receive either OPDIVO QVANTIG (n=248) or intravenous nivolumab (n=247). Fifty-seven percent of patients weighed <80 kg and 43% weighed ≥80 kg.

Baseline Karnofsky performance status was Patient distribution by IMDC risk categories was 21% favorable, 62% intermediate, and 17% poor. When comparing subcutaneous administration of OPDIVO QVANTIG to the intravenous administration of nivolumab, CHECKMATE-67T met the predefined acceptance margin for pharmacokinetic endpoints, with the lower boundary of 90% confidence interval of geometric mean ratios of not less than 0.8 for both serum nivolumab C avg over 28 days and C min at steady state. Efficacy results are shown in Table 49.

Table 49: Efficacy Results - CHECKMATE-67T a Confidence interval based on the Clopper and Pearson method. OPDIVO QVANTIG N=248 Intravenous Nivolumab N=247 ORR per BICR, n (%) 60 45 95% CI a RCC Trials - Intravenous Nivolumab The effectiveness of OPDIVO QVANTIG has been established for the following: • as monotherapy, for advanced renal cell carcinoma (RCC) following treatment with intravenous nivolumab and ipilimumab combination therapy (CHECKMATE-214 study). • in combination with cabozantinib, for the first-line treatment of adult patients with advanced RCC (CHECKMATE-9ER study). • as monotherapy, for the treatment of adult patients with advanced RCC who have received prior anti-angiogenic therapy (CHECKMATE-025 study). Use of OPDIVO QVANTIG for these RCC indications is supported by evidence from adequate and well-controlled studies conducted with intravenous nivolumab, and additional pharmacokinetic and safety data that demonstrated comparable pharmacokinetics and safety profiles between OPDIVO QVANTIG and intravenous nivolumab in the CHECKMATE-67T trial.

Below is a description of the efficacy results of these adequate and well-controlled studies of intravenous nivolumab in these RCC populations. First-line Renal Cell Carcinoma CHECKMATE-214 CHECKMATE-214 (NCT02231749) was a randomized (1:1), open-label trial in patients with previously untreated advanced RCC. Patients were included regardless of their PD-L1 status.

CHECKMATE-214 excluded patients with any history of or concurrent brain metastases, active autoimmune disease, or medical conditions requiring systemic immunosuppression. Patients were stratified by International Metastatic RCC Database Consortium (IMDC) prognostic score and region. Efficacy was evaluated in intermediate/poor risk patients with at least 1 or more of 6 prognostic risk factors as per the IMDC criteria (less than one year from time of initial renal cell carcinoma diagnosis to randomization, Karnofsky performance status <80%, hemoglobin less than the lower limit of normal, corrected calcium of >10 mg/dL, platelet count greater than the upper limit of normal, and absolute neutrophil count greater than the upper limit of normal).

Treatment continued until disease progression or unacceptable toxicity. The trial population characteristics were: median age was 61 years range: years of age and 8% ≥75 years of age. The major efficacy outcome measures were OS, PFS (independent radiographic review committee -assessed) and confirmed ORR (IRRC-assessed) in intermediate/poor risk patients.

In this population, the trial demonstrated statistically significant improvement in OS and ORR for patients randomized to intravenous nivolumab and ipilimumab as compared with sunitinib (Table 50 and Figure 1). OS benefit was observed regardless of PD-L1 expression level. The trial did not demonstrate a statistically significant improvement in PFS.

Efficacy results are shown in Table 50 and Figure 1. Table 50: Efficacy Results - CHECKMATE-214 (Intermediate/Poor Risk Population) - CHECKMATE-214 CHECKMATE-214 also randomized 249 favorable risk patients as per IMDC criteria to intravenous nivolumab and ipilimumab (n=125) or to sunitinib (n=124). These patients were not evaluated as part of the efficacy analysis population.

OS in favorable risk patients receiving intravenous nivolumab and ipilimumab compared to sunitinib has a hazard ratio of The efficacy of intravenous nivolumab and ipilimumab in previously untreated renal cell carcinoma with favorable-risk disease has not been established. CHECKMATE-9ER CHECKMATE-9ER (NCT03141177) was a randomized, open-label study of intravenous nivolumab combined with cabozantinib versus sunitinib in patients with previously untreated advanced RCC. CHECKMATE-9ER excluded patients with autoimmune disease or other medical conditions requiring systemic immunosuppression.

Patients were stratified by IMDC prognostic score (favorable vs. intermediate vs. poor), PD-L1 tumor expression (≥1% vs. <1% or indeterminate), and region (US/Canada/Western Europe/Northern Europe vs. Rest of World). Treatment beyond RECIST‑defined disease progression was permitted if the patient was clinically stable and considered to be deriving clinical benefit by the investigator.

Patient distribution by IMDC risk categories was 22% favorable, 58% intermediate, and 20% poor. The major efficacy outcome measure was PFS (BICR assessed). Additional efficacy outcome measures were OS and ORR (BICR assessed).

The trial demonstrated a statistically significant improvement in PFS, OS, and ORR for patients randomized to intravenous nivolumab and cabozantinib compared with sunitinib. Consistent results for PFS were observed across pre-specified subgroups of IMDC risk categories and PD-L1 tumor expression status. An updated OS analysis was conducted when 271 deaths were observed based on the pre-specified number of deaths for the pre-planned final analysis of OS.

Efficacy results are shown in Table 51 and Figures 2 and 3. Table 51: Efficacy Results - CHECKMATE-9ER - CHECKMATE-9ER In an exploratory analysis, the updated analysis of OS in patients with IMDC favorable, intermediate, intermediate/poor, and poor risk demonstrated a HR (95% CI) of 1.03, 0.74, 0.65, and 0.49, respectively. oq-os-checkmate-214 oq-pfs-checkmate-9er oq-updated-os-checkmate-9er Previously Treated Renal Cell Carcinoma CHECKMATE-025 CHECKMATE-025 (NCT01668784) was a randomized (1:1), open-label trial in patients with advanced RCC who had experienced disease progression during or after one or two prior anti-angiogenic therapy regimens. Patients were stratified by region, Memorial Sloan Kettering Cancer Center (MSKCC) Risk Group and the number of prior anti-angiogenic therapies.

Patients were randomized to nivolumab 3 mg/kg by intravenous infusion every 2 weeks (n=410) or everolimus 10 mg orally daily (n=411). The first tumor assessments were conducted 8 weeks after randomization and continued every 8 weeks thereafter for the first year and then every 12 weeks until progression or treatment discontinuation, whichever occurred later. The major efficacy outcome measure was overall survival (OS).

The trial population characteristics were: median age was 62 years range: years of age and 9% ≥75 years of age. The majority of patients (77%) were treated with one prior anti-angiogenic therapy. Patient distribution by MSKCC risk groups was 34% favorable, 47% intermediate, and 19% poor.

The trial demonstrated a statistically significant improvement in OS for patients randomized to intravenous nivolumab as compared with everolimus at the prespecified interim analysis when 398 events were observed (70% of the planned number of events for final analysis). Efficacy results are shown in Table 52 and Figure 4. Table 52: Efficacy Results - CHECKMATE-025 Unresectable or Metastatic Melanoma Previously Treated Metastatic Melanoma The effectiveness of OPDIVO QVANTIG has been established for the treatment of previously treated unresectable or metastatic melanoma in adult and pediatric patients 12 years and older who weigh 30 kg or greater.

Use of OPDIVO QVANTIG for this indication is supported by evidence from an adequate and well-controlled study conducted with intravenous nivolumab, and additional pharmacokinetic and safety data that demonstrated comparable pharmacokinetics and safety profiles between OPDIVO QVANTIG and intravenous nivolumab. Below is a description of the efficacy results of this adequate and well-controlled study of intravenous nivolumab in this melanoma population. Patients were required to have progression of disease on or following ipilimumab treatment and, if BRAF V600 mutation positive, a BRAF inhibitor.

The trial excluded patients with autoimmune disease, medical conditions requiring systemic immunosuppression, ocular melanoma, active brain metastasis, or a history of Grade 4 ipilimumab-related adverse reactions (except for endocrinopathies) or Grade 3 ipilimumab‑related adverse reactions that had not resolved or were inadequately controlled within 12 weeks of the initiating event. Tumor assessments were conducted 9 weeks after randomization then every 6 weeks for the first year, and every 12 weeks thereafter. Efficacy was evaluated in a single-arm, non-comparative, planned interim analysis of the first 120 patients who received intravenous nivolumab in CHECKMATE-037 and in whom the minimum duration of follow-up was 6 months.

The major efficacy outcome measures in this population were confirmed overall response rate (ORR) as measured by blinded independent central review using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and duration of response. There were responses in patients with and without BRAF V600 mutation-positive melanoma. Figure 5 summarizes the OS results.

Figure 5: Overall Survival - CHECKMATE-037* The primary OS analysis was not adjusted to account for subsequent therapies, with 54 (40.6%) patients in the chemotherapy arm subsequently receiving an anti-PD1 treatment. OS may be confounded by dropout, imbalance of subsequent therapies, and differences in baseline factors. CHECKMATE-066 CHECKMATE-066 (NCT01721772) was a multicenter, double-blind, randomized (1:1) trial in 418 patients with BRAF V600 wild-type unresectable or metastatic melanoma.

Randomization was stratified by PD-L1 status (≥5% of tumor cell membrane staining by immunohistochemistry vs. <5% or indeterminate result) and M stage (M0/M1a/M1b versus M1c). Key eligibility criteria included histologically confirmed, unresectable or metastatic, cutaneous, mucosal, or acral melanoma; no prior therapy for metastatic disease; completion of prior adjuvant or neoadjuvant therapy at least 6 weeks prior to randomization; ECOG performance status 0 or 1; absence of autoimmune disease; and absence of active brain or leptomeningeal metastases. The trial excluded patients with ocular melanoma.

Additional outcome measures included investigator-assessed progression-free survival (PFS) and ORR per RECIST v1.1. More patients in the intravenous nivolumab arm had an ECOG performance status of 0 (71% vs. 58%). CHECKMATE-066 demonstrated a statistically significant improvement in OS for the intravenous nivolumab arm compared with the dacarbazine arm in an interim analysis based on 47% of the total planned events for OS.

Efficacy results are shown in Table 53 and Figure 6. Table 53: Efficacy Results - CHECKMATE-066 - CHECKMATE-066 CHECKMATE-067 CHECKMATE-067 (NCT01844505) was a multicenter, randomized (1:1:1), double-blind trial in 945 patients with previously untreated, unresectable or metastatic melanoma to one of the following arms: intravenous nivolumab and ipilimumab, intravenous nivolumab, or ipilimumab. Patients were required to have completed adjuvant or neoadjuvant treatment at least 6 weeks prior to randomization and have no prior treatment with anti-CTLA-4 antibody and no evidence of active brain metastasis, ocular melanoma, autoimmune disease, or medical conditions requiring systemic immunosuppression.

Randomization was stratified by PD-L1 expression (≥5% vs. <5% tumor cell membrane expression) as determined by a clinical trial assay, BRAF V600 mutation status, and M stage per the AJCC staging system (M0, M1a, M1b vs. M1c). The major efficacy outcome measures were investigator-assessed PFS per RECIST v1.1 and OS.

CHECKMATE-067 demonstrated statistically significant improvements in OS and PFS for patients randomized to either intravenous nivolumab-containing arm as compared with the ipilimumab arm. The trial was not designed to assess whether adding ipilimumab to intravenous nivolumab improves PFS or OS compared to intravenous nivolumab as a single agent. Efficacy results are shown in Table 54 and Figure 7.

Based on a minimum follow-up of 28 months, the proportion of responses lasting ≥24 months was 55% in the intravenous nivolumab and ipilimumab arm, 56% in the intravenous nivolumab arm, and 39% in the ipilimumab arm. oq-os-checkmate-066 oq-os-checkmate-067 oq-os-checkmate-037

Adjuvant Treatment of Melanoma

The effectiveness of OPDIVO QVANTIG has been established for the adjuvant treatment of Stage IIB, Stage IIC, Stage III, or Stage IV melanoma in adult and pediatric patients 12 years and older who weigh 30 kg or greater. CHECKMATE-76K CHECKMATE-76K (NCT04099251) was a randomized, double-blind trial in 790 patients with completely resected Stage IIB/C melanoma. Enrollment required complete resection of the primary melanoma with negative margins and a negative sentinel lymph node within 12 weeks prior to randomization, and ECOG performance status of 0 or 1.

The trial excluded patients with ocular/uveal or mucosal melanoma, autoimmune disease, any condition requiring systemic treatment with either corticosteroids (≥10 mg daily prednisone or equivalent) or other immunosuppressive medications, as well as patients with prior therapy for melanoma except surgery. Randomization was stratified by AJCC 8 th staging system edition T3b vs. T4a vs.

T4b. The major efficacy outcome measure was recurrence-free survival (RFS) defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant metastasis), new primary melanoma, or death, from any cause, whichever occurred first and as assessed by the investigator. Sixty one percent had stage IIB and 39% had stage IIC melanoma.

CHECKMATE-76K demonstrated a statistically significant improvement in RFS for patients randomized to the intravenous nivolumab arm compared with the placebo arm. Efficacy results are shown in Table 55 and Figure 8. Table 55: Efficacy Results - CHECKMATE-76K - CHECKMATE-76K CHECKMATE-238 CHECKMATE-238 (NCT02388906) was a randomized, double-blind trial in 906 patients with completely resected Stage IIIB/C or Stage IV melanoma.

Enrollment required complete resection of melanoma with margins negative for disease within 12 weeks prior to randomization. Randomization was stratified by PD-L1 status (positive vs. negative/indeterminate) and AJCC stage Stage IIIB/C vs. Stage IV M1a-M1b vs.

Stage IV M1c. Patients underwent imaging for tumor recurrence every 12 weeks for the first 2 years then every 6 months thereafter. Efficacy results are shown in Table 56 and Figure 9.

Table 56: Efficacy Results - CHECKMATE-238 - CHECKMATE-238 oq-rfs-checkmate-76k oq-rfs-checkmate-238

Neoadjuvant Treatment of Resectable Non-Small Cell Lung Cancer The effectiveness of OPDIVO QVANTIG has been established for the neoadjuvant treatment of resectable (tumors ≥4 cm or node positive) NSCLC in combination with platinum doublet chemotherapy. CHECKMATE-816 CHECKMATE-816 (NCT02998528) was a randomized, open label trial in patients with resectable NSCLC. The trial included patients with resectable, histologically confirmed Stage IB (≥4 cm), II, or IIIA NSCLC (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging criteria), ECOG performance status 0 or 1, and measurable disease (per RECIST version 1.1).

Patients with unresectable or metastatic NSCLC, known EGFR mutations or ALK translocations, Grade 2 or greater peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded from the study. Stratification factors for randomization were tumor PD-L1 expression level (≥1% versus <1% or non-quantifiable), disease stage (IB/II versus IIIA), and sex (male versus female). The major efficacy outcome measures were event-free survival (EFS) based on blinded independent central review (BICR) assessment and pathologic complete response (pCR) as evaluated by blinded independent pathology review (BIPR).

Additional efficacy outcome measures included OS. A total of 358 patients were randomized to receive either intravenous nivolumab in combination with platinum‑doublet chemotherapy (n=179) or platinum-doublet chemotherapy (n=179). Eighty-three percent of patients in the intravenous nivolumab in combination with platinum-doublet chemotherapy arm had definitive surgery compared to 75% of patients in the platinum-doublet chemotherapy arm.

The study demonstrated statistically significant improvements in EFS and pCR. Efficacy results are presented in Table 57 and Figure 10. Table 57: Efficacy Results - CHECKMATE-816 Figure 10: Event-Free Survival - CHECKMATE-816 At the time of the EFS analysis, 26% of the patients had died.

A prespecified interim analysis for OS resulted in a HR of which did not cross the boundary for statistical significance. oq-efs-checkmate-816

CHECKMATE-77T The efficacy of intravenous nivolumab, in combination with platinum-doublet chemotherapy, followed by surgery, and continued adjuvant treatment with intravenous nivolumab as a single agent, was investigated in CHECKMATE-77T (NCT04025879), a randomized, double-blind trial in 461 patients with resectable NSCLC. The trial included patients with resectable, suspected or histologically confirmed Stage IIA (>4 cm) to IIIB (T3-T4 N2) NSCLC (per the 8th edition American Joint Committee on Cancer (AJCC) Staging Manual), and ECOG performance status 0 or 1. Randomization was stratified by tumor PD-L1 expression level (≥1% versus <1% versus indeterminate/not evaluable), disease stage (Stage II versus Stage III), and tumor histology (squamous versus nonsquamous).

Within 90 days after the surgery, placebo was administered intravenously over 30 minutes every 4 weeks. All study medications were administered via intravenous infusion. The trial was not designed to isolate the effect of intravenous nivolumab in each phase (neoadjuvant or adjuvant) of treatment.

The major efficacy outcome measure was event-free survival (EFS) based on BICR assessment. Additional efficacy outcome measures included overall survival (OS), pathologic complete response (pCR), and major pathologic response (MPR). Seventy-eight percent of patients in the neoadjuvant intravenous nivolumab in combination with platinum-doublet chemotherapy followed by adjuvant intravenous nivolumab arm had definitive surgery compared to 77% of patients in the neoadjuvant placebo and platinum-doublet chemotherapy followed by placebo arm.

The study demonstrated a statistically significant improvement in EFS for patients treated with neoadjuvant intravenous nivolumab in combination with platinum-doublet chemotherapy followed by single agent intravenous nivolumab compared with patients randomized to placebo in combination with platinum-doublet chemotherapy followed by placebo. Efficacy results are presented in Table 58 and Figure 11. Table 58: Efficacy Results - CHECKMATE-77T Figure 11: Event-Free Survival - CHECKMATE-77T In a pre-specified descriptive analysis, the pCR rate was in the intravenous nivolumab arm and in the placebo arm.

At the time of the EFS analysis, OS data were immature. oq-efs-checkmate-77t

Metastatic Non-Small Cell Lung Cancer Second-line Treatment of Metastatic NSCLC The effectiveness of OPDIVO QVANTIG has been established for the treatment of NSCLC previously treated with platinum-based chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving OPDIVO QVANTIG. CHECKMATE-017 CHECKMATE-017 (NCT01642004) was a randomized (1:1), open-label trial in 272 patients with metastatic squamous NSCLC who had experienced disease progression during or after one prior platinum doublet-based chemotherapy regimen.

Randomization was stratified by prior paclitaxel vs. other prior treatment and region (US/Canada vs. Europe vs. Rest of World).

This trial included patients regardless of their PD-L1 status. The trial excluded patients with autoimmune disease, medical conditions requiring systemic immunosuppression, symptomatic interstitial lung disease, or untreated brain metastasis. Patients with treated brain metastases were eligible if neurologically returned to baseline at least 2 weeks prior to enrollment, and either off corticosteroids, or on a stable or decreasing dose of <10 mg daily prednisone equivalents.

The major efficacy outcome measure was OS. Additional efficacy outcome measures were investigator-assessed ORR and PFS. The trial population characteristics were: median age was 63 years range: years of age and 11% ≥75 years of age.

Baseline ECOG performance status was were former/current smokers. Baseline disease characteristics of the population as reported by investigators were Stage IIIb (19%), Stage IV (80%), and brain metastases (6%). All patients received prior therapy with a platinum-doublet regimen and 99% of patients had tumors of squamous-cell histology.

Efficacy results are shown in Table 59 and Figure 12. Table 59: Efficacy Results - CHECKMATE-017 - CHECKMATE-017 Archival tumor specimens were retrospectively evaluated for PD-L1 expression. Across the trial population, 17% of 272 patients had non-quantifiable results.

In pre-specified exploratory subgroup analyses, the hazard ratios for survival were in the PD-L1 negative subgroup and in the PD-L1 positive subgroup. Appropriate prior targeted therapy in patients with known sensitizing EGFR mutation or ALK translocation was allowed. Randomization was stratified by prior maintenance therapy (yes vs. no) and number of prior therapies (1 vs. 2).

In addition, prespecified analyses were conducted in subgroups defined by PD-L1 expression. Baseline ECOG performance status was 0 had previously treated brain metastases. Prior therapy included platinum-doublet regimen (100%) and 40% received maintenance therapy as part of the first-line regimen.

Histologic subtypes included adenocarcinoma (93%), large cell (2.4%), and bronchoalveolar (0.9%). CHECKMATE-057 demonstrated a statistically significant improvement in OS for patients randomized to intravenous nivolumab as compared with docetaxel at the prespecified interim analysis when 413 events were observed (93% of the planned number of events for final analysis). Efficacy results are shown in Table 60 and Figure 13.

Table 60: Efficacy Results - CHECKMATE-057 - CHECKMATE-057 Archival tumor specimens were evaluated for PD-L1 expression following completion of the trial. Across the trial population, 22% of 582 patients had non-quantifiable results. Figures 14 and 15 summarize the results of prespecified analyses of OS and PFS in subgroups determined by percentage of tumor cells expressing PD-L1.

Figure 14: Forest Plot: OS Based on PD-L1 Expression - CHECKMATE-057 Figure 15: Forest Plot: PFS Based on PD-L1 Expression - CHECKMATE-057 oq-os-checkmate-017 oq-os-checkmate-057 oq-forest-plot-os-checkmate-057 oq-forest-plot-pfs-checkmate-057

Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck The effectiveness of OPDIVO QVANTIG has been established for the treatment of recurrent or metastatic squamous cell carcinoma of the head and neck with disease progression on or after platinum-based therapy. CHECKMATE-141 CHECKMATE-141 (NCT02105636) was a randomized (2:1), active-controlled, open-label trial enrolling patients with metastatic or recurrent SCCHN who had experienced disease progression during or within 6 months of receiving platinum-based therapy administered in either the adjuvant, neo-adjuvant, primary (unresectable locally advanced) or metastatic setting. The trial excluded patients with autoimmune disease, medical conditions requiring immunosuppression, recurrent or metastatic carcinoma of the nasopharynx, squamous cell carcinoma of unknown primary histology, salivary gland or non-squamous histologies (e.g., mucosal melanoma), or untreated brain metastasis.

Randomization was stratified by prior cetuximab treatment (yes/no). The trial demonstrated a statistically significant improvement in OS for patients randomized to intravenous nivolumab as compared with investigator’s choice at a pre-specified interim analysis (78% of the planned number of events for final analysis). Efficacy results are shown in Table 61 and Figure 16.

Table 61: - CHECKMATE-141 Archival tumor specimens were retrospectively evaluated for PD-L1 expression using the PD-L1 IHC 28-8 pharmDx assay. Across the trial population, 28% (101/361) of patients had non-quantifiable results. In pre-specified exploratory subgroup analyses, the hazard ratio for survival was with median survivals of 5.7 and 5.8 months for the nivolumab and chemotherapy arms, respectively, in the PD-L1 negative subgroup.

The HR for survival was with median survivals of 8.7 and 4.6 months for the nivolumab and chemotherapy arms, respectively, in the PD-L1 positive SCCHN subgroup. oq-os-checkmate-141

Urothelial Carcinoma Adjuvant Treatment of Urothelial Carcinoma (UC) at High Risk of Recurrence The effectiveness of OPDIVO QVANTIG has been established for the adjuvant treatment of UC at high risk of recurrence. CHECKMATE-274 CHECKMATE-274 (NCT02632409) was a randomized, double-blind, placebo‑controlled study of adjuvant intravenous nivolumab in patients who were within 120 days of radical resection (R0) of UC of the bladder or upper urinary tract (renal pelvis or ureter) at high risk of recurrence. High risk of recurrence was defined as either 1 ypT2-ypT4a or ypN + for patients who received neoadjuvant cisplatin or 2 pT3-pT4a or pN + for patients who did not receive neoadjuvant cisplatin and who also either were ineligible for or refused adjuvant cisplatin.

Patients were stratified by pathologic nodal status (N+ vs. N0/x with <10 nodes removed vs. N0 with ≥10 nodes removed), tumor cells expressing PD-L1 (≥1% vs. <1%/indeterminate as determined by the central lab using the PD‑L1 IHC 28-8 pharmDx assay), and use of neoadjuvant cisplatin (yes vs. no).

ECOG performance status was Tumor PD-L1 expression was ≥1% in 40% of patients, and 21% of patients had upper tract UC. The major efficacy outcome measures were investigator-assessed DFS in all randomized patients and in patients with tumors expressing PD-L1 ≥1%. DFS was defined as time to first recurrence (local urothelial tract, local non-urothelial tract, or distant metastasis), or death.

At the pre-specified interim analysis, CHECKMATE-274 demonstrated a statistically significant improvement in DFS for patients randomized to intravenous nivolumab vs. placebo in the all randomized patient population, as well as in the subpopulation of patients with PD-L1 ≥1%, as shown in Table 62 and Figure 17. In exploratory subgroup analyses in patients with upper tract UC (n=149), no improvement in DFS was observed in the nivolumab arm compared to the placebo arm. The unstratified DFS hazard ratio estimate was In an exploratory subgroup analysis in patients with PD-L1 expression of <1% (n=414), the unstratified DFS hazard ratio estimate was OS data is immature with 33% of deaths in the overall randomized population.

In the UTUC subpopulation, 37 deaths occurred (20 in the nivolumab arm, 17 in the placebo arm). Table 62: Efficacy Results - CHECKMATE-274 Patients - CHECKMATE-274 oq-dfs-checkmate-274 First-line Treatment of Unresectable or Metastatic UC The effectiveness of OPDIVO QVANTIG has been established for the first-line treatment of unresectable or metastatic UC in combination with cisplatin and gemcitabine. CHECKMATE-901 CHECKMATE-901 (NCT 03036098) was a randomized, open-label study in patients with previously untreated unresectable or metastatic UC.

Prior neoadjuvant or adjuvant chemotherapy were permitted as long as the disease recurrence took place ≥12 months from completion of therapy. Patients who were ineligible for cisplatin and those with active CNS metastases were excluded. Stratification factors for randomization were PD-L1 status (≥1% vs. <1% or indeterminate) and liver metastasis.

The major efficacy outcome measures were OS and PFS as assessed by BICR using RECIST v1.1. Additional efficacy outcome measures included ORR as assessed by BICR. Baseline ECOG performance status was Forty-nine (16%) in the intravenous nivolumab in combination with cisplatin-based chemotherapy arm and 43 (14%) in the cisplatin-based chemotherapy arm switched from cisplatin to carboplatin after at least one cycle of cisplatin.

Efficacy results are presented in Table 63 and Figures 18 and 19. Table 63: Efficacy Results – CHECKMATE-901 - CHECKMATE-901 oq-os-checkmate-901 oq-pfs-checkmate-901 Previously Treated Advanced or Metastatic Urothelial Carcinoma The effectiveness of OPDIVO QVANTIG has been established for the treatment of patients with locally advanced or metastatic UC and disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. CHECKMATE-275 CHECKMATE-275 (NCT02387996) was a single-arm trial in 270 patients with locally advanced or metastatic UC who had disease progression during or following platinum-containing chemotherapy or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen.

Patients were excluded for active brain or leptomeningeal metastases, active autoimmune disease, medical conditions requiring systemic immunosuppression, and ECOG performance status >1. Patients received nivolumab 3 mg/kg by intravenous infusion every 2 weeks until unacceptable toxicity or either radiographic or clinical progression. Tumor response assessments were conducted every 8 weeks for the first 48 weeks and every 12 weeks thereafter.

Major efficacy outcome measures included confirmed ORR as assessed by IRRC using RECIST v1.1 and DOR. Twenty-seven percent had non-bladder urothelial carcinoma and 84% had visceral metastases. Thirty-four percent of patients had disease progression following prior platinum-containing neoadjuvant or adjuvant therapy.

Twenty-nine percent of patients had received ≥2 prior systemic regimens in the metastatic setting. Thirty-six percent of patients received prior cisplatin only, 23% received prior carboplatin only, and 7% were treated with both cisplatin and carboplatin in the metastatic setting. Forty-six percent of patients had an ECOG performance status of 1.

Eighteen percent of patients had a hemoglobin <10 g/dL, and twenty-eight percent of patients had liver metastases at baseline. Tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory and the results were used to define subgroups for pre-specified analyses. The remaining 54% of patients were classified as having PD-L1 expression of <1% (defined as <1% of tumor cells expressing PD-L1).

Confirmed ORR in all patients and the two PD-L1 subgroups are shown in Table 64. Median time to response was 1.9 months (range: 1.6-7.2). In 77 patients who received prior systemic therapy only in the neoadjuvant or adjuvant setting, the ORR was Table 64: Efficacy Results - CHECKMATE-275

Microsatellite Instability-High or Mismatch Repair Deficient Metastatic Colorectal Cancer Treatment of MSI-H or dMMR mCRC The effectiveness of OPDIVO QVANTIG has been established for the treatment of unresectable or metastatic microsatellite instability-high or mismatch repair deficient colorectal cancer (CRC) in adult and pediatric patients 12 years and older who weigh 30 kg or greater following treatment with intravenous nivolumab and ipilimumab combination therapy. CHECKMATE-8HW CHECKMATE-8HW (NCT03143153) was a randomized, 3-arm, open-label trial in immunotherapy-naive patients across all lines of therapy with unresectable or metastatic CRC with known tumor MSI-H or dMMR (MSI-H/dMMR) status as determined in accordance with local standard of practice using PCR, NGS or IHC, assays. Central assessment of MSI-H status using PCR (Idylla MSI) test and dMMR status using IHC (Omnis MMR) test was conducted retrospectively on patient tumor specimens used for local MSI-H/dMMR status determination.

Patients with confirmed MSI-H/dMMR status by either central test comprised the primary study population. The trial excluded patients with brain metastasis that were symptomatic, had active autoimmune disease, used systemic corticosteroids or immunosuppressants, or had been treated with checkpoint inhibitors. Randomization was stratified by tumor location (right vs left) and by prior lines of therapy (0, 1, 2L+).

Patients randomized to the chemotherapy arm could receive intravenous nivolumab in combination with ipilimumab upon progression assessed by BICR. Study treatment was administered until disease progression, unacceptable toxicity, or for up to 2 years for patients who received intravenous nivolumab plus ipilimumab or intravenous nivolumab monotherapy. Patients who discontinued combination therapy because of an adverse reaction attributed to ipilimumab were permitted to continue intravenous nivolumab as a single agent.

Intravenous nivolumab with or without ipilimumab could be administered beyond RECIST 1.1-assessed progressive disease if there was a clinical benefit as determined by investigator and therapy was tolerated. The evaluation of efficacy relied on the comparison of patients with centrally confirmed MSI-H/dMMR mCRC randomized to intravenous nivolumab in combination with ipilimumab versus chemotherapy in the first line (1L) setting and the comparison of patients with centrally confirmed MSI-H/dMMR mCRC randomized to intravenous nivolumab plus ipilimumab vs intravenous nivolumab in all lines setting. Baseline ECOG performance status was number of prior lines of therapy was and tumor location was right-sided or left-sided for 69% and 31% of patients, respectively.

The baseline characteristics in patients with centrally confirmed MSI-H/dMMR is consistent with that of all randomized patients. First-Line intravenous nivolumab in combination with ipilimumab Among 303 patients in the first-line setting who were randomly assigned to intravenous nivolumab in combination with ipilimumab and to chemotherapy, 171 and 84 patients had centrally confirmed MSI-H/dMMR status in intravenous nivolumab in combination with ipilimumab arm and chemotherapy arm, respectively. The BICR-assessed PFS efficacy results for patients with centrally confirmed MSI-H/dMMR randomized to the intravenous nivolumab and ipilimumab arm compared with chemotherapy in the 1L setting are presented in Table 65 and Figure 20.

The comparative results of ORR and OS between arms were not available at the time of the PFS analysis due to statistical testing strategy. Table 65: Efficacy Results, First-Line - CHECKMATE-8HW (First-Line Intravenous Nivolumab + Ipilimumab vs Chemotherapy) - CHECKMATE-8HW oq-pfs-1l-checkmate-8hw All lines intravenous nivolumab in combination with ipilimumab Among 707 patients across all treatment lines who were randomly assigned to intravenous nivolumab in combination with ipilimumab and to intravenous nivolumab single agent, 296 and 286 patients had centrally confirmed MSI-H/dMMR status in the intravenous nivolumab in combination with ipilimumab arm and in the intravenous nivolumab arm, respectively. The BICR-assessed PFS and ORR efficacy results for patients with centrally confirmed MSI-H/dMMR randomized to the intravenous nivolumab in combination with ipilimumab compared with intravenous nivolumab single agent across all treatment lines setting are presented in Table 66 and Figure 21.

CHECKMATE-142 CHECKMATE-142 (NCT02060188) was a multicenter, non-randomized, multiple parallel-cohort, open-label trial conducted in patients with locally determined dMMR or MSI-H metastatic CRC (mCRC) who had disease progression during or after prior treatment with fluoropyrimidine‑, oxaliplatin‑, or irinotecan-based chemotherapy. Key eligibility criteria were at least one prior line of treatment for metastatic disease, ECOG performance status 0 or 1, and absence of the following: active brain metastases, active autoimmune disease, or medical conditions requiring systemic immunosuppression. Patients enrolled in the single agent intravenous nivolumab MSI-H mCRC cohort received nivolumab 3 mg/kg by intravenous infusion (IV) every 2 weeks.

Treatment in both cohorts continued until unacceptable toxicity or radiographic progression. A total of 74 patients were enrolled in the single-agent MSI-H mCRC intravenous nivolumab cohort. Baseline ECOG performance status was were reported to have Lynch Syndrome.

Across the 74 patients, 72% received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; received prior lines of therapy for metastatic disease, respectively, and 42% of patients had received an anti-EGFR antibody. A total of 119 patients were enrolled in the intravenous nivolumab and ipilimumab MSI-H mCRC cohort. Across the 119 patients, 69% had received prior treatment with a fluoropyrimidine, oxaliplatin, and irinotecan; received prior lines of therapy for metastatic disease, respectively, and 29% had received an anti-EGFR antibody.

Efficacy results for each of these single-arm cohorts are shown in Table 67. Table 67: Efficacy Results - CHECKMATE-142

Hepatocellular Carcinoma First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma (HCC) The effectiveness of OPDIVO QVANTIG has been established for the treatment of hepatocellular carcinoma following treatment with intravenous nivolumab and ipilimumab combination therapy. CHECKMATE-9DW (NCT04039607) was a randomized (1:1), open-label trial in adults (18 years of age or older) with unresectable or metastatic HCC. Patients had histologically confirmed HCC, Child Pugh Class A, ECOG performance status 0 or 1, and no prior systemic therapy for advanced disease.

Esophagogastroduodenoscopy was not mandated prior to enrollment. The trial excluded patients with active autoimmune disease, brain or leptomeningeal metastases, a history of hepatic encephalopathy (within 12 months of randomization), a platelet count <60,000, clinically significant ascites, medical conditions requiring systemic immunosuppression, infection with HIV, or active co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) or HBV and hepatitis D virus (HDV). HCV vs. non-viral, macrovascular invasion and/or extrahepatic spread (present or absent), and alpha-fetoprotein levels (≥400 or <400 ng/mL).

The primary efficacy outcome measure was OS in all randomized patients. Additional efficacy measures included BICR-assessed ORR and DOR based on RECIST 1.1 criteria. A total of 668 patients were randomized to receive intravenous nivolumab in combination with ipilimumab (n=335) or investigator’s choice (n=333) of lenvatinib or sorafenib.

In the investigator arm, 85% and 15% of treated patients received lenvatinib or sorafenib, respectively. Baseline ECOG performance status was Thirty-four percent (34%) of patients had HBV infection, 28% had HCV infection, and 36% had no evidence of HBV or HCV infection. Nineteen percent (19%) of patients had alcoholic liver disease and 11% had non-alcoholic fatty liver disease.

The majority of patients had BCLC stage C (73%) disease at baseline, 19% had stage B, and 6% had stage A. Patients with Child-Pugh scores of respectively; 1 patient with Child Pugh 8 was enrolled. CHECKMATE-9DW demonstrated a statistically significant improvement in OS and ORR.

The minimum follow-up was 26.8 months. Efficacy results are shown in Table 68 and Figure 22. Table 68: Efficacy Results - CHECKMATE-9DW - CHECKMATE-9DW oq-os-checkmate-9dw Previously Treated Hepatocellular Carcinoma The effectiveness of OPDIVO QVANTIG has been established for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have been previously treated with sorafenib following treatment with intravenous nivolumab and ipilimumab.

CHECKMATE-040 CHECKMATE-040 (NCT01658878) was a multicenter, multiple cohort, open-label trial that evaluated the efficacy of intravenous nivolumab as a single agent and in combination with ipilimumab in patients with hepatocellular carcinoma (HCC) who progressed on or were intolerant to sorafenib. Additional eligibility criteria included histologic confirmation of HCC and Child‑Pugh Class A cirrhosis. The trial excluded patients with active autoimmune disease, brain metastasis, a history of hepatic encephalopathy, clinically significant ascites, infection with HIV, or active co‑infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) or HBV and hepatitis D virus (HDV); however, patients with only active HBV or HCV were eligible.

The major efficacy outcome measure was confirmed overall response rate as assessed by BICR using RECIST v1.1 and modified RECIST (mRECIST) for HCC. Duration of response was also assessed. Baseline ECOG performance status was Fifty-seven (57%) percent of patients had active HBV infection, 8% had active HCV infection, and 35% had no evidence of active HBV or HCV.

The etiology for HCC was alcoholic liver disease in 16% and non‑alcoholic fatty liver disease in 6% of patients. Prior cancer treatment history included surgery (74%), radiotherapy (29%), or local treatment (59%). All patients had received prior sorafenib, of whom 10% were unable to tolerate sorafenib; 29% of patients had received 2 or more prior systemic therapies.

Efficacy results are shown in Table 69. The results for intravenous nivolumab in combination with ipilimumab in Cohort 4 are based on a minimum follow-up of 28 months. Table 69: Efficacy Results - Cohort 4 of CHECKMATE-040

Esophageal Cancer Adjuvant Treatment of Resected Esophageal or Gastroesophageal Junction Cancer The effectiveness of OPDIVO QVANTIG has been established for the adjuvant treatment of resected esophageal or gastroesophageal junction cancer with residual pathologic disease who have received neoadjuvant chemoradiotherapy (CRT). CHECKMATE-577 CHECKMATE-577 (NCT02743494) was a randomized, multicenter, double-blind trial in 794 patients with completely resected (negative margins) esophageal or gastroesophageal junction cancer who had residual pathologic disease following concurrent chemoradiotherapy (CRT). Treatment was until disease recurrence, unacceptable toxicity, or for up to 1 year in total duration.

Enrollment required complete resection within 4 to 16 weeks prior to randomization. The trial excluded patients who did not receive CRT prior to surgery, had stage IV resectable disease, autoimmune disease, or any condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone or equivalent) or other immunosuppressive medications. Randomization was stratified by tumor PD-L1 status (≥1% vs. <1% or indeterminate or non-evaluable), pathologic lymph node status (positive ≥ypN1 vs. negative ypN0), and histology (squamous vs. adenocarcinoma).

The major efficacy outcome measure was disease-free survival (DFS) defined as the time between the date of randomization and the date of first recurrence (local, regional, or distant from the primary resected site) or death, from any cause, whichever occurred first as assessed by the investigator prior to subsequent anti-cancer therapy. The baseline Tumor PD-L1 status ≥1% was positive for 16% of patients and negative for 72% of patients. DFS benefit was observed regardless of tumor PD-L1 expression and histology.

Efficacy results are shown in Table 70 and Figure 23. Table 70: Efficacy Results - CHECKMATE-577 - CHECKMATE-577 oq-dfs-checkmate-577 First-line Treatment of Unresectable Advanced or Metastatic Esophageal Squamous Cell Carcinoma (ESCC) Whose Tumors Express PD-L1 (≥1) The effectiveness of OPDIVO QVANTIG in combination with fluoropyrimidine- and platinum-containing chemotherapy has been established for the first-line treatment of unresectable advanced or metastatic ESCC. CHECKMATE-648 CHECKMATE-648 (NCT03143153) was a randomized, active-controlled, open-label trial in patients with previously untreated unresectable advanced, recurrent or metastatic ESCC (squamous or adenosquamous histology).

The trial enrolled patients whose tumor was evaluable for tumor cell (TC) PD-L1 expression, which was evaluated using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory. A retrospective scoring of a patient’s tumor PD-L1 status using Combined Positive Score (CPS), was also conducted using the PD-L1-stained tumor specimens used for randomization. Patients were not amenable to chemoradiation or surgery with curative intent.

Prior treatment with curative intent was allowed if completed more than six months prior to trial enrollment. The trial excluded patients with brain metastasis that were symptomatic, had active autoimmune disease, used systemic corticosteroids or immunosuppressants, or patients at high risk of bleeding or fistula due to apparent invasion of tumor to organs adjacent to the esophageal tumor. In patients who received intravenous nivolumab in combination with chemotherapy and in whom either fluorouracil and/or cisplatin were discontinued, other components of the treatment regimen were allowed to be continued.

Randomization was stratified by TC PD-L1 expression (≥1% vs. <1% or indeterminate), region East Asia vs. Rest of Asia vs. The major efficacy outcome measures were OS and BICR-assessed PFS in patients with TC PD-L1 expression ≥1%.

Additional efficacy measures included OS in all randomized patients, BICR-assessed PFS in all randomized patients, and ORR assessed by BICR in TC PD-L1 expression ≥1% and in all randomized patients. The tumor assessments per RECIST v1.1 were conducted every 6 weeks up to and including week 48, then every 12 weeks thereafter. Patients had histological confirmation of squamous cell carcinoma (99%) or adenosquamous cell carcinoma (1.7%) in the esophagus.

Baseline ECOG performance status was A statistically significant improvement in OS was demonstrated in patients randomized to intravenous nivolumab in combination with chemotherapy and patients randomized to intravenous nivolumab in combination with ipilimumab compared with chemotherapy. An exploratory analysis of OS in patients with PD-L1 CPS <1 showed a HR of for the comparison of intravenous nivolumab in combination with chemotherapy, and the exploratory analysis OS in patients with PD-L1 CPS <1 showed a HR of for the comparison of intravenous nivolumab in combination with ipilimumab; these results indicate that the improvement in the ITT population was primarily attributed to the results observed in the subgroup of patients with PD-L1 CPS ≥1. Efficacy results are shown in Table 71 and Figures 24 and 25.

Table 71: Efficacy Results - CHECKMATE-648 A-OS in CPS CHECKMATE 648 B-OS in TC PD L1 CHECKMATE 648.jpg A-PFS in CPS CHECKMATE 648.jpg B-PFS in TC PD L1 CHECKMATE 648.jpg Previously Treated Unresectable Advanced, Recurrent or Metastatic ESCC The effectiveness of OPDIVO QVANTIG has been established for the treatment of unresectable advanced, recurrent, or metastatic ESCC after prior fluoropyrimidine- and platinum-based chemotherapy. ATTRACTION-3 ATTRACTION-3 (NCT02569242) was a multicenter, randomized (1:1), active-controlled, open‑label trial in patients with unresectable advanced, recurrent, or metastatic ESCC, who were refractory or intolerant to at least one fluoropyrimidine- and platinum‑based regimen. The trial enrolled patients regardless of PD-L1 status, but tumor specimens were evaluated prospectively using the PD-L1 IHC 28-8 pharmDx assay at a central laboratory.

The trial excluded patients who were refractory or intolerant to taxane therapy, had brain metastases that were symptomatic or required treatment, had autoimmune disease, used systemic corticosteroids or immunosuppressants, or had apparent tumor invasion of organs adjacent to the esophageal tumor or had stents in the esophagus or respiratory tract. Randomization was stratified by region Japan vs. Patients were treated until disease progression, assessed by the investigator per RECIST v1.1, or unacceptable toxicity.

Sixty-seven percent of patients had received one prior systemic therapy regimen and 26% had received two prior systemic therapy regimens prior to enrolling in ATTRACTION‑3. Baseline ECOG performance status was ATTRACTION-3 demonstrated a statistically significant improvement in OS for patients randomized to intravenous nivolumab as compared with investigator’s choice of taxane chemotherapy. OS results by PD-L1 CPS level (<1 and ≥1) were not studied.

The minimum follow-up was 17.6 months. Efficacy results are shown in Table 72 and Figure 26. Table 72: Efficacy Results - ATTRACTION-3 of tumor cells expressing PD-L1.

The remaining 52% had PD-L1 negative ESCC defined as <1% of tumor cells expressing PD-L1. In a pre-specified exploratory analysis by PD-L1 status, the hazard ratio (HR) for OS was with median survivals of 10.9 and 8.1 months for the intravenous nivolumab and investigator’s choice arms, respectively, in the PD-L1 positive subgroup. In the PD-L1 negative subgroup, the HR for OS was with median survivals of 10.9 and 9.3 months for the intravenous nivolumab and investigator’s choice arms, respectively. oq-os-attraction-3

Gastric Cancer, Gastroesophageal Junction Cancer, and Esophageal Adenocarcinoma Whose Tumors Express PD-L1 (≥1) The effectiveness of OPDIVO QVANTIG in combination with fluoropyrimidine- and platinum-containing chemotherapy has been established for the treatment of gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. CHECKMATE-649 CHECKMATE-649 (NCT02872116) was a randomized, multicenter, open-label trial in patients (n=1581) with previously untreated advanced or metastatic gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma. The trial excluded patients who were known human epidermal growth factor receptor 2 (HER2) positive, or had untreated CNS metastases.

Patients were randomized to receive intravenous nivolumab in combination with chemotherapy (n=789) or chemotherapy (n=792). Patients were treated until disease progression, unacceptable toxicity, or up to 2 years. Randomization was stratified by tumor cell PD-L1 status (≥1% vs. <1% or indeterminate), region Asia vs.

US vs. Rest of World, ECOG performance status (0 vs. 1), and chemotherapy regimen (mFOLFOX6 vs. CapeOX).

The major efficacy outcome measures, assessed in patients with PD-L1 CPS ≥5, were PFS assessed by BICR and OS. Baseline ECOG performance status was Seventy percent of patients had adenocarcinoma tumors in the stomach, 17% in the gastroesophageal junction, and 13% in the esophagus. CHECKMATE-649 demonstrated a statistically significant improvement in OS and PFS for patients with PD-L1 CPS ≥5.

Statistically significant improvement in OS was also demonstrated for all randomized patients and patients with PD-L1 CPS ≥1. Exploratory analysis of OS in the CPS <1 population showed a hazard ratio of indicating that the improvement in the ITT population was primarily attributed to the results observed in the subgroup of patients with PD-L1 CPS ≥1. The minimum follow-up was 12.1 months.

Efficacy results are shown in Table 73 and Figures 27 and 28.