Datroway Drug Information
Generic name: DATOPOTAMAB DERUXTECAN
Uses of Datroway
Locally Advanced or Metastatic
EGFR-Mutated Non-Small Cell Lung Cancer (NSCLC) DATROWAY is indicated for the treatment of adult patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) who have received prior EGFR-directed therapy and platinum-based chemotherapy. This indication is approved under accelerated approval based on objective response rate and duration of response . Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trial.
Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)
DATROWAY is indicated for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy.
Unresectable or Metastatic, HR-Positive
HER2-Negative Breast Cancer DATROWAY is indicated for the treatment of adult patients with unresectable or metastatic, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
Dosage & Administration of Datroway
| Preservative-free lubricant eye drops | |
| Steroid-containing mouthwash (dexamethasone oral solution 0.1 mg/mL) | |
| Diphenhydramine (25 to 50 mg) administered intravenously or orally | |
| Acetaminophen (650 to 1,000 mg) administered intravenously or orally | |
| 5-HT3 serotonin receptor antagonist or appropriate alternatives intravenously or oral |
Side Effects of Datroway
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflects exposure to DATROWAY in 1365 patients as a single agent at 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity. This included 137 patients with NSCLC in TROPION-Lung05 , 297 patients with NSCLC in TROPION-Lung01 , 360 patients with HR-positive, HER2-negative breast cancer in TROPION-Breast01 , 319 patients with TNBC in TROPION-Breast02 , 50 patients with NSCLC and 83 patients with breast cancer in TROPION-PanTumor01 (NCT03401385), and 40 patients with NSCLC and 79 patients with breast cancer in TROPION-PanTumor02 (NCT05460273). Among the 1365 patients who received DATROWAY, 48% were exposed for greater than 6 months and 22% were exposed for greater than one year.
In this pooled safety population, the most common (≥20%) adverse reactions were stomatitis (63%), nausea (51%), fatigue (42%), alopecia (38%), constipation (30%), vomiting (23%), decreased appetite (22%), and rash (20%). In this pooled safety population, the most common (≥2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (8%), decreased hemoglobin (3.7%), decreased sodium (3.0%), and decreased blood potassium (2.3%). Locally Advanced or Metastatic EGFR-Mutated Non-Small Cell Lung Cancer TROPION-Lung05, TROPION-Lung01, TROPION-PanTumor01 The safety of DATROWAY was evaluated in 125 patients with EGFR-mutated NSCLC who received DATROWAY 6 mg/kg administered as an intravenous infusion once every 3 weeks (21-day cycle) until disease progression or unacceptable toxicity in TROPION-Lung05 and TROPION-Lung01 as well as TROPION-PanTumor01 (NCT03401385). Among these patients, the median duration of treatment was 6.1 months (range 0.7 months to 41.7 months). The median age was 63 years (range: 36 to 81), 56% of patients were <65 years, 62% of patients were female; 66% were Asian, 26% were White, 0.8% were Black, 6% were other races; and 2.4% were of Hispanic ethnicity. Serious adverse reactions occurred in 26% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were COVID-19 (4%), stomatitis (2.4%), and pneumonia (1.6%). Fatal adverse reactions occurred in 1.6% of patients who received DATROWAY, due to death not otherwise specified. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 8% of patients.
Adverse reactions which resulted in permanent discontinuation of DATROWAY in >1% of patients included ILD/pneumonitis (2.4%) and abnormal hepatic function (1.6%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 43% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (13%), stomatitis (7%), fatigue (6%), pneumonia (4%), anemia (2.4%), amylase increased (2.4%), keratitis (2.4%), ILD/pneumonitis (1.6%), decreased appetite (1.6%), dyspnea (1.6%), rash (1.6%), and infusion-related reaction (1.6%). Dose reductions of DATROWAY due to an adverse reaction occurred in 26% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (14%), keratitis (1.6%), fatigue (1.6%), decreased weight (1.6%) and COVID-19 (1.6%). The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, alopecia, fatigue, decreased hemoglobin, decreased lymphocytes, constipation, increased calcium, increased AST, decreased white blood cell count, increased lactate dehydrogenase, musculoskeletal pain, decreased appetite, increased ALT, and rash.
Table 4: Adverse Reactions (≥10%) in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 Adverse Reaction DATROWAY N=125 All Grades % Grades 3 or 4 % Events were graded using NCI CTCAE v5.0. Gastrointestinal disorders Stomatitis Includes other related terms 71 9 Nausea 50 0 Constipation 31 0 Vomiting 16
Diarrhea 12 0 Skin and subcutaneous tissue disorders Alopecia 49 0 Rash
20
Pruritus 12 0 General disorders and administration site conditions Fatigue Includes fatigue
asthenia, and malaise 42 6 Musculoskeletal and connective tissue disorders Musculoskeletal pain 22
Metabolism and nutrition disorders Decreased appetite 20 1.6 Infections and Infestations
COVID-19 19
Respiratory, Thoracic, and Mediastinal Disorders Cough 18 0 Dyspnea 11 2.4 Eye
disorders Dry eye 13 0 Keratitis Includes corneal disorder, corneal erosion, keratitis, punctate keratitis, and ulcerative keratitis 12
Injury, poisoning and procedural complications Infusion-related reaction 13 0 Nervous system disorders
Headache 13 0 Clinically relevant adverse reactions occurring in <10% of patients who received DATROWAY included dry skin, blurred vision, abdominal pain, conjunctivitis, dry mouth, ILD/pneumonitis, skin hyperpigmentation, increased lacrimation, and visual impairment. Table 5: Select Laboratory Abnormalities (≥20%) that Worsened from Baseline in Patients with Locally Advanced or Metastatic EGFR-Mutated NSCLC Who Received DATROWAY in TROPION-Lung05, TROPION-Lung01, and TROPION-PanTumor01 Laboratory Abnormality Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities. DATROWAY The denominator used to calculate the rate varied from 115 to 124 based on the number of patients with a baseline value and at least one post-treatment value.
All Grades % Grades 3 or 4 % Hematology Decreased hemoglobin 34
Decreased lymphocytes 32 11 Decreased white blood cell count 27 1.6 Chemistry
Increased calcium 31 0 Increased AST 28
Increased lactate dehydrogenase 23 0 Increased
ALT 20
Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)
TROPION-Breast02 The safety of DATROWAY was evaluated in 319 patients with triple-negative breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast02. DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 8.5 months (range: 0.7 months to 38.0 months) for patients who received DATROWAY. Serious adverse reactions occurred in 17% of patients who received DATROWAY. Serious adverse reactions in >1% of patients who received DATROWAY were pneumonia (2.2%), vomiting (1.9%), COVID-19 (1.6%), and anemia (1.3%). Fatal adverse reactions occurred in one patient (0.3%) who received DATROWAY and was due to ILD/pneumonitis. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 4.7% of patients.
Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (0.9%) and keratitis (0.9%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 35% of patients. Adverse reactions which required dosage interruption in >1% of patients included stomatitis (5%), increased amylase (4.1%), keratitis (3.4%), neutropenia (3.1%), COVID-19 (2.8%), pneumonia (2.2%), dry eye (1.9%), upper respiratory tract infection (1.6%), anemia (1.3%), leukopenia (1.3%), IRR (1.3%), and ILD/pneumonitis (1.3%). Dose reductions of DATROWAY due to an adverse reaction occurred in 28% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (11%), keratitis (4.1%), fatigue (3.8%), increased amylase (2.8%), and pneumonia (1.3%). The most common (≥20%) adverse reactions, including laboratory abnormalities in patients receiving DATROWAY, were stomatitis, increased amylase, nausea, alopecia, decreased hemoglobin, decreased white blood cells, constipation, decreased calcium, decreased lymphocytes, fatigue, decreased neutrophils, increased ALT, increased AST, dry eye, keratitis, decreased albumin, vomiting, musculoskeletal pain, decreased sodium, and increased blood alkaline phosphatase.
Table 6: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast02 Adverse Reactions DATROWAY N=319 Chemotherapy N=309 All Grades % Grades 3 or 4 % All Grades % Grades 3 or 4 % Events were graded using NCI CTCAE v5.0. Gastrointestinal Disorders Stomatitis Includes other related terms 63 8 14
Nausea 48 0.6 22 0.6 Constipation 40 0.3 17 0 Vomiting 23
1.6 11
Skin and Subcutaneous Tissue Disorders Alopecia 43 0 35 0.3 Rash Includes
rash, erythematous rash, maculo-papular rash, pruritic rash 16 0.6 10
Skin hyperpigmentation Includes pigmentation disorder, skin discoloration, skin hyperpigmentation 10 0 0.3
0 General Disorders Fatigue 36 2.8 32
Eye Disorders Keratitis Includes corneal disorder, corneal epithelium defect, corneal erosion, corneal
exfoliation, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, ulcerative keratitis 26 6 2.8
Dry eye 26 1.3 4.9 0 Musculoskeletal and connective tissue disorders Musculoskeletal
pain 22 0.6 22
Respiratory, Thoracic, and Mediastinal Disorders Cough 19 0 14 0 Metabolism and
Nutrition Disorders Decreased appetite 19 0.6 8
Clinically relevant adverse reactions occurring in <10% of patients who received
DATROWAY included infusion-related reactions including anaphylactic reaction, diarrhea, conjunctivitis, lacrimation increased, dry mouth, dry skin, pruritus, rhinorrhea, blepharitis, meibomian gland dysfunction, blurred vision, ILD/pneumonitis, visual impairment, photophobia, and madarosis. Table 7: Select Laboratory Abnormalities (≥20%) in Patients Who Received DATROWAY in TROPION-Breast02 Laboratory Abnormality DATROWAY The denominator used to calculate the rate varied from 235 to 317 based on the number of patients with a baseline value and at least one post-treatment value. Chemotherapy All Grades % Grades 3 or 4 % All Grades % Grades 3 or 4 % Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities.
Hematology Decreased hemoglobin 43 3.8 63 6 Decreased white blood cells 41 0.9 58 10 Decreased lymphocytes 36 6 46 7 Decreased neutrophils 35 3.5 48 14 Chemistry Increased amylase 54 38 8 0 Decreased calcium 39 1.9 44
Increased
ALT 28 1.6 26
Increased
AST 27 1.6 26
Decreased albumin 25 1.0 20 0.3 Decreased sodium 21 3.5 18 2.7
Increased blood alkaline phosphatase 20 0.3 15 0 Unresectable or Metastatic, HR-Positive, HER2-Negative Breast Cancer TROPION-Breast01 The safety of DATROWAY was evaluated in 360 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer who received at least one dose of DATROWAY 6 mg/kg in TROPION-Breast01 . DATROWAY was administered by intravenous infusion once every three weeks. The median duration of treatment was 6.7 months (range: 0.7 months to 16.1 months) for patients who received DATROWAY. Serious adverse reactions occurred in 15% of patients who received DATROWAY. Serious adverse reactions in >0.5% of patients who received DATROWAY were urinary tract infection (1.9%), COVID-19 infection (1.7%), ILD/pneumonitis (1.1%), acute kidney injury, pulmonary embolism, vomiting, diarrhea, hemiparesis, and anemia (0.6% each). Fatal adverse reactions occurred in 0.3% of patients who received DATROWAY and were due to ILD/pneumonitis. Permanent discontinuation of DATROWAY due to an adverse reaction occurred in 3.1% of patients.
Adverse reactions which resulted in permanent discontinuation of DATROWAY in >0.5% of patients included ILD/pneumonitis (1.7%) and fatigue (0.6%). Dosage interruptions of DATROWAY due to an adverse reaction occurred in 22% of patients. Adverse reactions which required dosage interruption in >1% of patients included COVID-19 (3.3%), infusion-related reaction (1.4%), ILD/pneumonitis (1.9%), stomatitis (1.9%), fatigue (1.7%), keratitis (1.4%), acute kidney injury (1.1%), and pneumonia (1.1%). Dose reductions of DATROWAY due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dose reduction in >1% of patients included stomatitis (13%), fatigue (3.1%), nausea (2.5%), and weight decrease (1.9%). The most common (≥20%) adverse reactions, including laboratory abnormalities, were stomatitis, nausea, fatigue, decreased leukocytes, decreased calcium, alopecia, decreased lymphocytes, decreased hemoglobin, constipation, decreased neutrophils, dry eye, vomiting, increased ALT, keratitis, increased AST, and increased alkaline phosphatase.
Table 8: Adverse Reactions (≥10%) in Patients Who Received DATROWAY in TROPION-Breast01 Adverse Reactions DATROWAY N=360 Chemotherapy N=351 All Grades % Grades 3 or 4 % All Grades % Grades 3 or 4 % Events were graded using NCI CTCAE v5.0. Gastrointestinal Disorders Stomatitis Includes other related terms. 59 7 17
Nausea 56 1.4 27 0.6 Constipation 34 0.3 17 0 Vomiting 24
1.1 12
Diarrhea 11 0.6 19 1.4 Abdominal pain 11 0.6 15 1.4 General
Disorders and Administration Site Conditions Fatigue Includes fatigue, asthenia, lethargy, malaise 44 4.2 40
Skin and Subcutaneous Tissue Disorders Alopecia 38 0 22 0 Rash 19
0 17
Eye Disorders Dry eye 27 0.8 13 0 Keratitis Includes corneal disorder
corneal erosion, corneal infiltrates, corneal lesion, corneal toxicity, injury corneal, keratitis, keratopathy, punctate keratitis, and ulcerative keratitis 24 1.1 10 0 Metabolism and Nutrition Disorders Decreased appetite 16 1.4 16
Infections and Infestations
COVID-19 16 1.4 13
Respiratory, Thoracic, and Mediastinal Disorders Cough 15 0 10 0 Clinically relevant
adverse reactions occurring in <10% of patients who received DATROWAY included infusion-related reactions (including bronchospasm), ILD/pneumonitis, headache, pruritus, dry skin, dry mouth, conjunctivitis, blepharitis, meibomian gland dysfunction, blurred vision, increased lacrimation, photophobia, visual impairment, skin hyperpigmentation, and madarosis. Table 9: Select Laboratory Abnormalities (≥20%) in Patients Who Received DATROWAY in TROPION-Breast01 Laboratory Abnormality DATROWAY The denominator used to calculate the rate varied from 264 to 359 based on the number of patients with a baseline value and at least one post-treatment value. Chemotherapy All Grades % Grades 3-4 % All Grades % Grades 3-4 % Frequencies were based on NCI CTCAE v5.0 grade-derived laboratory abnormalities.
Hematology Decreased leukocytes 41 1.1 63 18 Decreased lymphocytes 36 9 42 11 Decreased hemoglobin 35 2.8 51
Increased
AST 23 1.9 28
Increased
ALT 24 1.7 31
Warnings & Cautions for Datroway
Interstitial Lung Disease/Pneumonitis
DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis. Locally Advanced or Metastatic NSCLC In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01, ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to first onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY due to ILD/pneumonitis.
Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients. Unresectable or Metastatic Breast Cancer In the pooled safety population of 841 patients with breast cancer from TROPION-Breast01, TROPION-Breast02, TROPION-PanTumor01 and TROPION-PanTumor02, ILD/pneumonitis occurred in 3.0% of patients treated with DATROWAY, including 0.4% of patients with Grade 3. There were two fatal cases (0.2%). The median time to first onset for ILD was 5.3 months (range: 1.1 months to 19.3 months) and with a median duration of 1.2 months (range: 0.3 to 5.2). Eight patients (1.0%) had DATROWAY withheld and 10 patients (1.2%) permanently discontinued DATROWAY due to ILD/pneumonitis.
Systemic corticosteroids were required in 64% (16/25) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients. Patients were excluded from clinical studies for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis.
Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed.
Ocular Adverse Reactions
DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. In the pooled safety population , ocular adverse reactions occurred in 38% of patients treated with DATROWAY. Forty-two patients (3.1%) experienced Grade 3 ocular adverse reactions, which included keratitis and dry eye, and four patients (0.3%) experienced a Grade 4 ocular adverse reaction of keratitis, corneal epithelium defect, corneal lesion, and conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (18%), keratitis (16%), increased lacrimation (6%), and conjunctivitis (5%). The median time to first onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 30 months) and with a median duration of 2.3 months (range: 0.03 to 19.5). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 8% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to dosage interruption in 4.3% of patients, dosage reductions in 2.8% of patients, and permanent discontinuation of DATROWAY in 0.9% of patients.
Patients with clinically significant corneal disease were excluded from clinical studies. Advise patients to use preservative-free lubricant eye drops at least four times daily and as needed for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional . Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, at end of treatment, and as clinically indicated.
While on treatment, conduct visual acuity testing and slit lamp examination every 3 cycles. Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity .
Stomatitis
DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis. In the pooled safety population, stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 19.8 months) and with a median duration of 1.1 months (range: 0.03 to 33.2). Stomatitis led to dosage interruption in 5% of patients, dosage reductions in 11% of patients, and permanent discontinuation of DATROWAY in 0.4% of patients.
In patients who received DATROWAY in TROPION-Breast01 and TROPION-Breast02, 39% and 51% respectively used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment. Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY. Monitor patients for signs and symptoms of stomatitis.
If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY.
Embryo-Fetal Toxicity
Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd , is genotoxic and affects actively dividing cells. Advise patients of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with DATROWAY and for 7 months after the last dose.
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with DATROWAY and for 4 months after the last dose.
Pregnancy Safety for Datroway
Pregnancy Risk Summary Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd, is genotoxic and affects actively dividing cells . There are no available data on the use of DATROWAY in pregnant women to inform a drug-associated risk. Advise patients of the potential risks to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data There were no animal reproductive or developmental toxicity studies conducted with datopotamab deruxtecan-dlnk.
Pediatric Use of Datroway
Pediatric Use Safety and effectiveness of DATROWAY have not been established in pediatric patients.
Clinical Studies of Datroway
Locally Advanced or Metastatic
EGFR-Mutated Non-Small Cell Lung Cancer The efficacy of DATROWAY was evaluated in a pooled subgroup of patients with locally advanced or metastatic EGFR-mutated NSCLC who were enrolled across two clinical studies: TROPION-Lung05 and TROPION-Lung01. TROPION-Lung05 (NCT04484142) was a global, multicenter, single-arm, open-label trial in patients with previously treated NSCLC with an actionable genomic alteration and TROPION-Lung01 (NCT04656652) was a global, multicenter, randomized, active-controlled, open-label trial in patients with previously treated NSCLC with or without an actionable genomic alteration. For both trials, eligible patients with EGFR-mutated NSCLC must have previously received an EGFR-directed therapy and platinum-based chemotherapy. Patients with a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening were ineligible.
Patients who had brain metastases that were untreated and symptomatic were also ineligible. Patients received DATROWAY 6 mg/kg by intravenous infusion every 3 weeks until unacceptable toxicity or disease progression. For the pooled efficacy population, the major efficacy outcome measure was overall response rate (ORR) by BICR per RECIST v1.1. An additional efficacy outcome was duration of response (DOR) by BICR. Efficacy was assessed in 114 patients with EGFR-mutated NSCLC. The median age was 63 years (range 36 to 81); 43% were ≥65 years of age; 63% were female; 70% were Asian and 22% were White; 1.8% were of Hispanic/Latino ethnicity; 68% had ECOG PS of 1 and 32% had ECOG PS of 0; and 33% had brain metastases at baseline.
Fifty-three percent (53%) of patients had tumors with exon 19 deletions, 34% had exon 21 L858R mutations, 28% had T790M mutations, 2.6% had exon 20 insertion mutations and 14% had other EGFR mutations. Four percent (4.4%) of patients received one prior line of systemic therapy, 39% received two prior lines of systemic therapy, and 57% received three or more prior lines of systemic therapy in the locally advanced or metastatic setting. All patients received prior EGFR-directed therapy including 84% receiving prior osimertinib; 99% received prior platinum-based chemotherapy and 28% received prior anti-PD-1/ PD-L1 therapy.
Efficacy results are summarized in Table 11. Table 11: Efficacy Results in TROPION-Lung05 and TROPION-Lung01 by BICR DATROWAY TL05 N=77 DATROWAY TL01 N=37 DATROWAY Pooled N=114 CI: confidence interval Overall Response Rate (95% CI) 45% 43% 45% Complete Response 5% 2.7% 4.4% Partial Response 40% 41% 40% Duration of Response Median, months (95% CI) 6.9 6.5 6.5 ≥6 months 49% 44% 47% ≥12 months 23% 6% 18% In the TROPION-Lung05 trial, a difference was noted between ORR by BICR and ORR assessed by investigator; investigator assessed ORR was 34% (95% CI: 23, 45). In the TROPION-Lung01 trial, ORR assessed by investigator was similar to ORR by BICR.
Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC)
TROPION-Breast02 The efficacy of DATROWAY was evaluated in TROPION-Breast02 (NCT05374512), a multicenter, open-label, randomized trial of 644 patients with unresectable or metastatic triple-negative breast cancer (TNBC) who had not received prior chemotherapy or other systemic anti-cancer therapy for unresectable or metastatic breast cancer. Patients with either de novo metastatic or recurrent disease were enrolled. The study enrolled patients with PD-L1–negative tumors and patients with PD-L1–positive tumors who were ineligible for PD-1/PD-L1 inhibitor treatment due to one of the following: prior (neo)adjuvant PD-1/PD-L1 inhibitor treatment, a comorbidity precluding PD-1/PD-L1 inhibitor use, or unavailability of a PD-1/PD-L1 inhibitor in their country.
Patients with known germline BRCA pathogenic variants were enrolled if they were ineligible for PARP inhibitor therapy. Patients with recurrent disease were expected to have been treated with (neo)adjuvant anthracycline and those with de novo metastatic disease were enrolled if treatment with anthracycline was contraindicated or not considered the best treatment option. Patients with stable brain metastases were included in the study.
Patients were excluded for a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, or clinically significant corneal disease at screening. Patients with ECOG performance status >1 were also excluded. Randomization was stratified by geographical region (United States, Canada and Europe or Rest of World), PD-L1 status (positive or negative) and disease-free interval (DFI) history (de novo or ≤12 months or >12 months). A total of 644 patients were randomized 1:1 to receive either DATROWAY 6 mg/kg (N=323) by intravenous infusion every 3 weeks or investigator's choice of chemotherapy (N=321), until unacceptable toxicity or disease progression.
The choice of chemotherapy was based on the patient's prior use of taxane and DFI history. Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: paclitaxel (28%), nab-paclitaxel (54%), capecitabine (2.2%), eribulin (11%) or carboplatin (4.7%). The major efficacy outcomes were progression-free survival (PFS) as assessed by BICR based on RECIST v.1.1 and overall survival (OS). Additional efficacy outcomes included ORR. The median age was 56 years (range: 23-85), 25% were ≥65 years and 99.7% were female; 44% were White, 4.2% were Black or African American, 44% were Asian, and 15% were of Hispanic/Latino ethnicity, 83% were not of Hispanic/Latino ethnicity and 2% had ethnicity not reported. At the time of randomization, 59% had ECOG PS 0 and 41% had ECOG PS of 1; 75% had visceral disease, 30% had liver metastases, and 10% had stable brain metastases.
Ninety percent (90%) of patients had PD-L1 negative disease and 10% of patients had PD-L1 positive disease. Thirty four percent (34%) of patients had de novo metastatic disease. DFI was ≤12 months in 21% of patients and >12 months in 45% of patients.
DFI was ≤6 months in 15% of patients. Fifty-six percent (56%) of patients had received anthracyclines in prior lines of therapy. The study demonstrated a statistically significant improvement in PFS and OS in patients randomized to DATROWAY compared to chemotherapy.
Efficacy results are shown in Table 12 and Figures 1 and 2. Table 12: Efficacy Results in TROPION-Breast02 DATROWAY (N=323) Chemotherapy (N=321) CI: Confidence interval Progression-Free Survival Assessed by BICR Number of events (%) 199 209 Median, months (95% CI) 10.8
Hazard ratio (95% CI)
Based on the stratified Cox proportional hazards model 0.57 p-value Two-sided p-value based on stratified log-rank test., p-value is compared with the allocated alpha of 0.01. < 0.0001 Overall Survival Number of events (%) 168 181 Median, months (95% CI) 23.7
Hazard ratio (95% CI) 0.79 p-value, p-value is compared with the allocated
alpha of 0.0499. 0.0290 Confirmed Objective Response Rate Patients with Measurable Disease, N 311 311 ORR (95% CI), % 64 30 Complete Response, (%) 8 3 Partial Response, (%) 56 28 Figure 1: Kaplan-Meier Plot of PFS in TROPION-Breast02 Figure 2: Kaplan-Meier Plot of OS in TROPION-Breast02 Chemical Structure Chemical Structure
Unresectable or Metastatic, HR-Positive
HER2-Negative Breast Cancer TROPION-Breast01 The efficacy of DATROWAY was evaluated in TROPION-Breast01 (NCT05104866), a multicenter, open-label, randomized trial of 732 patients with unresectable or metastatic HR-positive, HER2-negative (IHC 0, IHC1+ or IHC2+/ISH-) breast cancer. Eligible patients must have progressed on and deemed not suitable for further endocrine therapy. Patients were required to have received 1 or 2 lines of prior chemotherapy in the unresectable or metastatic disease setting.
Patients were excluded for a history of ILD/pneumonitis requiring treatment with steroids, ongoing ILD/pneumonitis, clinically active brain metastases, or clinically significant corneal disease at screening. Patients were also excluded for ECOG performance status >1. Randomization was stratified by previous lines of chemotherapy (one or two), prior treatment with a CDK4/6 inhibitor (yes or no), and geographical region. A total of 732 patients were randomized 1:1 to receive either DATROWAY 6 mg/kg (N=365) by intravenous infusion every 3 weeks or investigator's choice of chemotherapy (N=367) until unacceptable toxicity or disease progression.
Single agent chemotherapy was determined by the investigator before randomization from one of the following choices: eribulin (60%), capecitabine (21%), vinorelbine (10%), or gemcitabine (9%). The major efficacy outcomes were progression-free survival (PFS) as assessed by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 and overall survival (OS). Additional efficacy outcomes included confirmed objective response rate (ORR) and duration of response (DOR) by BICR. The median age was 55 years (range 28-86); 22% were ≥65 years; 99% were female; 48% were White, 41% were Asian, 1.5% were Black or African American, and 11% were of Hispanic/Latino ethnicity; 57% had ECOG PS of 0 and 42% had ECOG PS of 1; 97% had visceral disease, 72% had liver metastases, and 8% had stable brain metastases. Sixty percent (60%) of patients received prior endocrine therapy in the (neo)adjuvant setting, and 89% received prior endocrine therapy in the unresectable or metastatic setting. Eighty-three percent (83%) of patients had prior treatment with a CDK4/6 inhibitor.
All patients received prior chemotherapy regimens in the unresectable or metastatic setting (81% received prior taxanes; 64% received prior anthracyclines). Sixty-two percent (62%) of patients had 1 prior chemotherapy regimen and 38% of patients had 2 prior chemotherapy regimens for treatment of unresectable or metastatic disease. The study demonstrated a statistically significant improvement in PFS in patients randomized to DATROWAY compared to chemotherapy. Efficacy results are shown in Table 13 and Figure 3. Table 13: Efficacy Results in TROPION-Breast01 DATROWAY (n=365) Chemotherapy (n=367) CI: Confidence interval; NS: not statistically significant Progression-Free Survival Assessed by BICR Number of events (%) 212 235 Progressive Disease 201 218 Death 11 17 Median, months (95% CI) 6.9
Hazard ratio (95% CI)
Based on the stratified Cox proportional hazards model 0.63 p-value Two-sided p-value based on stratified log-rank test., p-value is compared with the allocated alpha of 0.01. < 0.0001 Overall Survival Number of events (%) 223 213 Median, months (95% CI) 18.6
Hazard ratio (95% CI) 1.01 p-value NS Confirmed Objective Response Rate n
(%) 133 84 (95% CI) 31, 42 19, 28 Complete Response n (%) 2 0 Partial Response n (%) 131 84 Duration of Response Median, months (95% CI) 6.7
Figure 3: Kaplan-Meier Plot of
PFS by BICR in TROPION-Breast01 Chemical Structure
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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