Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations (TROPION-LUNG01)

• Status: Recruiting
• Trial end date: 2024-06-27
• Target enrollment: 0
• Participant gender: All

Summary

This study will evaluate the efficacy, safety, and pharmacokinetics of DS-1062a versus docetaxel in participants with previously treated advanced or metastatic non-small cell lung cancer (NSCLC) without actionable genomic alterations.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Daiichi Sankyo, Inc.
• Collaborator: AstraZeneca
• Treatments: Docetaxel

Criteria

Inclusion Criteria:

Participants eligible for inclusion in the study must meet all inclusion criteria within 28 days of randomization into the study.

• Sign and date the inform consent form (ICF) prior to the start of any study specific qualification procedures.

• Adults ≥18 years (if the legal age of consent is >18 years old, then follow local regulatory requirements)

• Life expectancy ≥3 months

• Has pathologically documented NSCLC that:

1. Has stage IIIB, IIIC, or stage IV NSCLC disease at the time of randomization (based on the American Joint Committee on Cancer, Eighth Edition)

2. Has documented negative test results for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)

3. Has no known genomic alterations in ROS proto-oncogene 1 (ROS1), neurotrophic tyrosine receptor kinase (NTRK), proto oncogene B-raf (BRAF), or other actionable driver oncogenes with approved therapies (actionable genomic alteration)

• Has documentation of radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC

• Participant must meet 1 of the following prior therapy requirements for advanced or metastatic NSCLC:

1. Received platinum-based chemotherapy in combination with α-PD-1/α-PD-L1 monoclonal antibody as the only prior line of therapy

• Includes participants who received prior platinum-based chemo/radiotherapy with maintenance α-PD-1/α-PD-L1 monoclonal antibody for Stage III disease and relapsed/progressed within 6 months from the last dose of platinum-based chemotherapy

• Includes participants who received prior platinum-based chemo/radiotherapy (with or without maintenance α-PD-1/α-PD-L1 monoclonal antibody) for Stage III disease and subsequently received α-PD-1/α-PD-L1 monoclonal antibody therapy (with or without platinum-based chemotherapy) for recurrent disease

2. Received platinum-based chemotherapy and α-PD-1/α-PD-L1 monoclonal antibody (in either order) sequentially as the only 2 prior lines of therapy

• Must undergo a mandatory pre-treatment tumor biopsy procedure or, if available, a tumor biopsy that was recently collected (within 3 months of Screening) after completion of the most recent anticancer treatment regimen and of adequate size may be substituted for the mandatory pre-treatment biopsy procedure collected during Screening.

• Archival tumor tissue from initial diagnosis is required, to the extent that archival tumor tissue is available

• Measurable disease based on local imaging assessment using RECIST v1.1

• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1 at Screening

• Within 7 days before Cycle 1 Day 1, has adequate bone marrow, hepatic, and renal function

• Left ventricular ejection fraction (LVEF) ≥50% by either echocardiogram (ECHO) or multigated acquisition (MUGA) scan within 28 days before Cycle 1 Day 1

• Adequate blood clotting function defined as international normalized ratio/prothrombin time and either partial thromboplastin or activated partial thromboplastin time ≤1.5 × upper limit of normal (ULN)

• Adequate treatment washout period before Cycle 1 Day 1

• Females of childbearing potential must have a negative serum pregnancy test at screening and must be willing to use highly effective birth control from the time of enrollment up to 7 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel

• Males must be surgically sterile or must use a condom in addition to highly effective birth control if his partners are of reproductive potential from the time of enrollment and for at least 4 months after last dose of DS-1062a or for at least 6 months after the last dose of docetaxel

• Male participants must not freeze or donate sperm from the time of Screening and throughout the study period and for at least 4 months after the last dose of DS-1062a or for at least 6 months after the last dose of docetaxel

• Female participants must not donate, or retrieve for their own use, ova from the time of Screening and throughout the study period and for at least 7 months after the last dose of DS-1062a and for at least 6 months after the last dose of docetaxel

Exclusion Criteria:

• Mixed small-cell lung cancer (SCLC) and NSCLC histology

• Has spinal cord compression or clinically active central nervous system metastases, defined as untreated and symptomatic, or requiring therapy with corticosteroids or anticonvulsants to control associated symptoms. Participants with clinically inactive brain metastases may be included in the study. Participants with treated brain metastases who are no longer symptomatic and who require no treatment with corticosteroids or anticonvulsants may be included in the study if they have recovered from the acute toxic effect of radiotherapy.

• Has leptomeningeal carcinomatosis or metastasis

• Had prior treatment with:

• Any agent including antibody drug conjugate (ADC) containing a chemotherapeutic agent targeting topoisomerase I

• TROP2-targeted therapy

• Docetaxel as monotherapy or in combination with other agents

• Had prior treatment with platinum-based chemotherapy and prior immunotherapy for Stage II NSCLC disease (eg, in the neo-adjuvant or adjuvant setting) without subsequently meeting the prior therapy requirements for Stage III or metastatic NSCLC disease

• Has NSCLC disease that is eligible for definitive local therapy alone

• Uncontrolled or significant cardiovascular disease, including:

• Mean QT interval corrected for heart rate using Fridericia's formula >470 msec (based on the average of Screening triplicate 12-lead electrocardiogram [ECG] determinations).

• History of myocardial infarction within 6 months before Cycle 1 Day 1

• History of uncontrolled angina pectoris within 6 months before Cycle 1 Day 1

• Congestive heart failure (CHF) (New York Heart Association Class II to IV) at Screening. Participants with a history of Class II to IV CHF prior to Screening, must have returned to Class I CHF and have LVEF ≥50% (by either an ECHO or MUGA scan within 28 days before Cycle 1 Day 1) in order to be eligible.

• History of serious cardiac arrhythmia requiring treatment

• LVEF <50% by ECHO or MUGA scan within 28 days before Cycle 1 Day 1

• Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg) within 28 days before Cycle 1 Day 1

• Has a history of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening

• Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of study Cycle 1 Day 1, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.), or any autoimmune, connective tissue or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc.), or prior pneumonectomy.

• Significant third-space fluid retention (for example ascites or pleural effusion) and is not amenable for required repeated drainage.

• Clinically significant corneal disease

• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals; suspected infections (eg, prodromal symptoms); or inability to rule out infections

• Has known human immunodeficiency virus (HIV) infection that is not well controlled

• Active hepatitis B and/or hepatitis C infection, such as those with serologic evidence of viral infection within 28 days of Cycle 1 Day 1

• Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years.

• Toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet improved to NCI-CTCAE version 5.0 Grade ≤1 or baseline

• Has other primary malignancies, except adequately resected non-melanoma skin cancer, curatively treated in situ disease, or other solid tumors curatively treated, with no evidence of disease for ≥3 years

• Has a history of severe hypersensitivity reactions to either the drug substances, inactive ingredients (including but not limited to polysorbate 80) of DS-1062a or docetaxel, or monoclonal antibodies

• Pregnant or breastfeeding

• Have substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions