A phase I/II open-label platform study to evaluate the safety and efficacy of multiple amivantamab-based therapeutic combinations in participants with advanced, unresectable lung cancer
- Conditions
- Cancernresectable metastatic non-small cell lung cancer
- Registration Number
- ISRCTN23584582
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- All
- Target Recruitment
- 201
1. Aged 18 years old and over (or the legal age of consent in the jurisdiction in which the study is taking place) at the time of informed consent
2. Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) NSCLC (any histology)
For Phase I – Combination Dose Finding Confirmation:
Metastatic NSCLC progressed on or after standard of care systemic anti-cancer therapy and is declining other systemic treatment options, if any.
For Phase II – Dose Expansion:
1. Cohort 1A: MET exon 11 skipping mutation (without prior therapy for metastatic disease)
1.1. Metastatic NSCLC previously characterized as MET exon 11 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratory
1.2. 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
1.3. Adequate tumor tissue sample must be submitted to the sponsor
2. Cohort 1B: MET exon 11 skipping mutation (prior therapy)
2.1. Metastatic NSCLC previously characterized as MET exon 11 skipping mutation positive AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratory
2.2. 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
2.3. Adequate tumor tissue sample must be submitted to the sponsor before enrollment
3. Cohort 1C: MET amplification (prior therapy)
3.1. Metastatic NSCLC previously characterized as having MET amplification (=2 copy number of MET) AND lacking EGFR and ALK mutation, by a local test using a CLIA certified laboratory or an accredited laboratorya
3.2. Progression of metastatic disease on at least 1 but no more than 3 prior lines of standard of care therapy for metastatic disease
3.3. Submission of adequate archival or fresh tumor tissue, obtained following metastatic NSCLC diagnosis and after disease progression on the last systemic therapy is required
1. 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.
2. A female participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study.
3. A female participant must be either of the following: Not of childbearing potential, or of childbearing potential and practicing at least 1 highly effective method of contraception.
1. History of uncontrolled illness, including but not limited to:
1.1. Uncontrolled diabetes
1.2. 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). See also inclusion criterion 1013 and exclusion criterion 14 for considerations with respect to HIV and hepatitis infection, respectively.
1.3. Active bleeding diathesis
1.4. Impaired oxygenation requiring continuous oxygen supplementation
1.5. 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:
3.1. Amivantamab excipients
3.2. Capmatinib or its excipients
4. Participant has, or will have, any of the following:
4.1. 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.
4.2. 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).
5. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment.
6. The participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets.
7. Participant has a history of clinically significant cardiovascular disease including, but not limited to the following:
7.1 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.
7.2. 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)
7.3. Note: Participants with cardiac pacemakers who are clinically stable are eligible.
7.4. Uncontrolled (persistent) hypertension: systolic blood pressure >160 mmHg; diastolic blood pressure >100 mmHg
7.5. 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
7.6. Pericarditis/clinically significant pericardial effusion within 1 month prior to administration of the first dose of study treatment
7.7. Myocarditis
8. Participant received thoracic radiotherapy to lung fields =4 weeks prior to Cycle 1 Day
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method