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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Dr
Anna
Minchom
+44 (0)20 86426011
anna.minchom@icr.ac.uk
Ms
Nicola
Hall
+44 (0)7769 886528
nhall4@its.jnj.com
Unresectable metastatic non-small cell lung cancer
This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.
Background and study aims
NSCLC is the most common type of lung cancer and may have MET exon 14 skipping mutations (changes) and MET gene amplification (additions). Amivantamab and capmatinib target the MET gene and downregulate signals sent by the MET protein within cells, which may prevent the growth of cancer cells. This study is designed to assess if amivantamab and capmatinib can be safely administered as a combination therapy in Phase I and to see how effective it is in the treatment of lung cancer in participants with NSCLC with MET exon 14 skipping mutation or MET amplification in Phase II.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
You can take part if:
Current inclusion criteria:
ISA1 METalmark (now closed in UK):
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.
Added 25/09/2024:
ISA2 Polydamas:
1. Participant must have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) (any histology), and must have metastatic NSCLC at the time of enrollment: Phase 1 (Combination Dose Selection) Cohort; Metastatic NSCLC progressed on or after standard of care systemic anti-cancer therapy and participant is declining other systemic treatment options, if any;1. Participants without known mutations must have had disease progression on, or have intolerance to, prior platinum-based chemotherapy and PD-(L)1-targeted immunotherapy given concurrently or sequentially, OR 2. Participants with NSCLC characterized by known driver mutations must have had disease progression on, or have intolerance to, appropriate targeted therapies as per local standard of care. Participants may have received prior therapy with amivantamab as long as discontinuation was not due to toxicity. Participants with EGFR mutation must not have had an anti-PD-1/PD-L1 therapy, Phase 2 Expansion Cohorts; Cohort A: Participant’s tumor must have an EGFR exon19del or L858R mutation, as determined by local molecular testing, Cohort B: Participants must have tumors lacking known primary driver mutations and must have PD-L1 expression of greater than or equal to (>=)50 percentage (%), per local testing, and are treatment-naïve in the metastatic setting
2. Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, that has not been previously irradiated
3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Added 28/11/2024:
ISA3 SwalloWTail:
1. Be 18 years of age or older at the time of enrolment.
2. Have histologically or cytologically confirmed non-small cell lung cancer (NSCLC) and must have metastatic NSCLC at the time of enrolment.
Phase 1 (Combination Dose Selection) Cohort:
Metastatic NSCLC (any histology) progressed on or after systemic anti-cancer therapy:
- Participants with metastatic NSCLC without known mutations must have had disease progression on, or have intolerance to, prior platinum-based chemotherapy and immunotherapy given concurrently or sequentially; or,
- Participants with metastatic NSCLC characterised by known driver mutations must have had disease progression on, or have intolerance to, appropriate targeted therapies as per local standard of care (SoC).
Phase 2 Expansion Cohorts:
Cohort A: Participant must have histologically confirmed adenocarcinoma NSCLC lacking known primary driver mutations, as determined by local genomic testing followed by central confirmation. Participant must have had disease progression on or after platinum-based chemotherapy and immune checkpoint inhibitor and must have had no more than 3 prior lines of therapy.
Cohort B: Participant must have histologically confirmed squamous NSCLC tumours lacking known primary driver mutations, as determined by local genomic testing (when available) followed by central confirmation. Participant must have had disease progression on or after platinum-based chemotherapy and immune checkpoint inhibitor and must have had no more than 3 prior
lines of therapy.
3. Must have at least 1 measurable lesion, according to RECIST v1.1, that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 non-irradiated measurable lesion exists, it may undergo the diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumour assessment scans are performed at least 7 days after the
biopsy.
4. Participant may have brain metastases only if previously definitively treated, and participant is clinically stable and asymptomatic for more than 2 weeks and is off or receiving low-dose corticosteroid treatment (less than or equal to 10 mg prednisone or equivalent) for at least 2 weeks prior to start of study treatment.
5. Participant may have a prior malignancy (other than the disease under study) if the natural history or treatment is unlikely to interfere with an
You may not be able to take part if:
Current exclusion criteria:
ISA1 METalmark (now closed in UK):1. History of uncontrolled illness, including but not limited to:1.1. Uncontrolled diabetes1.2. 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 diathesis1.4. Impaired oxygenation requiring continuous oxygen supplementation1.5. Psychiatric illness or any other circumstances (including social circumstances) that would limit compliance with study requirements2. 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 excipients3.2. Capmatinib or its excipients4. 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 mmHg7.5. 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 treatment7.6. Pericarditis/clinically significant pericardial effusion within 1 month prior to administration of the first dose of study treatment7.7. Myocarditis8. Participant received thoracic radiotherapy to lung fields ≤4 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤2 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities.9. Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms.
Added 25/09/2024:ISA2 Polydamas:1. Participant has an 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),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 requirements2. Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening - Has an active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents3. Participant has received radiotherapy for palliative purposes less than 14 days prior to the first dose of study treatment4. Participant has a. (or has a history of) leptomeningeal disease (carcinomatous meningitis), b. spinal cord compression not definitively treated with surgery or radiation
Added 28/11/2024:ISA3 SwalloWTail:1. Phase 2 only: Participant has known oncogenic driver mutations as detected by local testing or by central circulating tumour deoxyribonucleic acid (ctDNA) testing.2. Participant has received radiotherapy for palliative purposes less than 14 days prior to the first dose of study treatment.3. Participant has:a. (Or has a history of) leptomeningeal disease (carcinomatous meningitis).b. Spinal cord compression not definitively treated with surgery or radiation.4. Participant has an uncontrolled illness.5. Participant has history of any significant drug allergy or has known allergies, hypersensitivity, or intolerance to either of the study drugs or their excipients.6. Medical history of (non-infectious) interstitial lung disease (ILD)/pneumonitis, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.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.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).4.3. Expected major surgery while the investigational agent is being administered or within 6 months after the last dose of study treatment.8. Participant has a history of clinically significant cardiovascular disease.9. Phase 2 only: Participant received prior amivantamab or docetaxel.10. Participant received live or live attenuated vaccine(s) within 3 months prior to screening or plans to receive such vaccines during the study.11. Participant has had prior chemotherapy, targeted cancer therapy, or treatment with an investigational anticancer agent within 2 weeks or 4 half-lives (whichever is longer) before administration of the first study treatment. For agents with long half-lives the maximum required time since last dose is 28 days.12. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less prior to the first dose of study treatment (except as per the protocol).13. Has taken immunosuppressive doses of systemic medications, such as corticosteroids within 2 weeks before the planned first dose of study treatment.14. Active hepatitis of infectious origin.15. Other clinically active liver disease of infectious origin.16. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments.
_____
Previous exclusion criteria:
1. History of uncontrolled illness, including but not limited to:1.1. Uncontrolled diabetes1.2. 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 diathesis1.4. Impaired oxygenation requiring continuous oxygen supplementation1.5. 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 excipients3.2. 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 mmHg7.5. 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 treatment7.6. Pericarditis/clinically significant pericardial effusion within 1 month prior to administration of the first dose of study treatment7.7. Myocarditis
8. Participant received thoracic radiotherapy to lung fields ≤4 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities. For all other anatomic sites (including radiotherapy to thoracic vertebrae and ribs), radiotherapy ≤2 weeks prior to Cycle 1 Day 1 or patients who have not recovered from radiotherapy-related toxicities.
9. Participant has symptomatic central nervous system (CNS) metastases which are neurologically unstable or have required increasing doses of steroids >10 mg prednisone or equivalent within the 2 weeks prior to study entry to manage CNS symptoms.
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Ms
Nicola
Hall
+44 (0)7769 886528
nhall4@its.jnj.com
Dr
Anna
Minchom
+44 (0)20 86426011
anna.minchom@icr.ac.uk
The study is sponsored by Janssen-Cilag International NV and funded by Cilag.
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
You can print or share the study information with your GP/healthcare provider or contact the research team directly.
