A Clinical Study to Evaluate the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
- Conditions
- nresectable Metastatic Non-small Cell Lung CancerMedDRA version: 21.1Level: PTClassification code 10061873Term: Non-small cell lung cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2022-000485-18-FR
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 141
Master protocol PLATFORMPANSC2001 - ISA 61186372PANSC2001
inclusion criteria
Age
1. =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent.
Disease Characteristics
2. Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) NSCLC (any histology).
3. Criterion modified per Amendment 1
3.1. For Phase 1 – Combination Dose Selection:
Metastatic NSCLC progressed on or after standard of care systemic anti-cancer therapy and is declining other systemic treatment options, if any:
- Participants must have had disease progression on or have intolerance to prior platinumbased chemotherapy and an anti-PD-(L)1 antibody given concurrently or sequentially OR
- Participants with targetable genomic aberrations must have had prior disease progression on or have intolerance to appropriate targeted therapies as per local standard of care Participants who may have received prior therapy with amivantamab and/or capmatinib as long as discontinuation was not due to toxicity.
4. Criterion modified per Amendment 1
4.1. For Phase 2 – Expansion:
- Cohort 1A: MET exon 14 skipping mutation (without prior therapy for metastatic disease)
- Metastatic NSCLC previously characterized as MET exon 14 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratory
- Participant must not have received systemic anti-cancer therapy for metastatic NSCLC. Neo-adjuvant and adjuvant therapies for earlier stage disease are allowed if relapse occurred >12 months from end of neoadjuvant or adjuvant systemic therapy
- Adequate tumor tissue sample must be submitted to the sponsor.
- Cohort 1B: MET exon 14 skipping mutation (prior therapy)
- Metastatic NSCLC previously characterized as MET exon 14 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratory
- Progression of metastatic disease on at least 1 but no more than 3 lines of prior systemic anti-cancer therapy, which may include MET TKI or chemotherapy as per local standard of care, but may not include prior amivantamab
- Participants who have received prior amivantamab will be excluded
- Adequate tumor tissue sample must be submitted to the sponsor.
- Cohort 1C: MET amplification (prior therapy)
- Metastatic NSCLC previously characterized as having MET amplification (=5 copy number of MET) AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratory
- Progression of metastatic disease on at least 1 but no more than 3 prior lines of standard of care therapy for metastatic disease
- Participants who have received prior amivantamab will be excluded
- Submission of adequate archival or fresh tumor tissue, obtained following metastatic NSCLC diagnosis and after disease progression on the last systemic therapy is required.
5. At least 1 measurable lesion, according to RECIST v1.1. Must not have been previously irradiated. May be used for the screening biopsy provided baseline tumor assessment scans are performed =7 days after the biopsy.
Brain and Central Nervous System Metastases
6. May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for >2 weeks and who are off or receiving low-dose corticosteroid treatment (=10 mg prednisone or equivalent) for at l
Master protocol PLATFORMPANSC2001 - ISA 61186372PANSC2001
exclusion criteria
Medical Conditions
1. History of uncontrolled illness, including but not limited to:
a. Uncontrolled diabetes
b. Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment] or diagnosed or suspected viral infection).
c. Active bleeding diathesis
d. Impaired oxygenation requiring continuous oxygen supplementation
e. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements
2. Medical history of (non-infectious) ILD/pneumonitis, or has current ILD/ pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
3. Known allergies, hypersensitivity, or intolerance to
a. amivantamab excipients.
b. capmatinib or its excipients.
4. Participant has, or will have, any of the following:
a. An invasive operative procedure with entry into a body cavity, within 4 weeks or without complete recovery before administration of the first study treatment. Thoracentesis, if needed, and percutaneous biopsy for baseline tumor tissue sample may be done less than 4 weeks prior to administration of the first study treatment, as long as the participant has adequately recovered from the procedure prior to the first dose of study treatment in the clinical judgement of the investigator.
b. Significant traumatic injury within 3 weeks before the start of administration of the first study treatment (all wounds must be fully healed prior to Day 1). Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment
5. The participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets.
6. Participant has a history of clinically significant cardiovascular disease including, but not limited to the following:
a. Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to administration of the first dose of study treatment, or any of the following within 6 months prior to administration of the first dose of study treatment: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary.
b. Prolonged QTc interval >480 msec or clinically significant cardiac arrhythmia or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
c. Note: Participants with cardiac pacemakers who are clinically stable are eligible
d. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg.
e. Congestive heart failure (CHF) defined as New York Heart Association (NYHA) class III-IV or hospitalization for CHF (any NYHA class) within
6 months of administration of the first study treatment.
f. Pericarditis/clinically significant pericardial effusion within 1 month prior to administration of the first dose of study treatment.
g. Myocarditis.
Disease Characteristics
7. Participant received thoracic radiotherapy to lung fields =4 weeks prior to Cycle 1 Day 1 or patients who have not recovered from r
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method