Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The purpose of this study is to identify the recommended Phase 2 combination dose (RP2CD\[s\]) of the amivantamab and capmatinib combination therapy in participants with non-small cell lung cancer (NSCLC) in Phase 1 (combination dose selection), and to evaluate the antitumor effect of the amivantamab and capmatinib combination therapy in mesenchymal-epithelial transition (MET) exon 14 skipping mutation and MET amplified NSCLC, when administered at the selected RP2CD(s) in Phase 2 (expansion).
Interventions
DRUGCapmatinib
Capmatinib will be administered orally.
DRUGAmivantamab
Amivantamab will be administered as IV infusion.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Previously diagnosed with histologically or cytologically confirmed unresectable Stage IV (metastatic) non-small cell lung cancer (NSCLC) (any histology) * May have: definitively, locally treated brain metastases that are clinically stable and asymptomatic for greater than (\>) 2 weeks and who are off or receiving low-dose corticosteroid treatment (less than or equal to \[\<=\]10 milligrams (mg) prednisone or equivalent) for at least 2 weeks prior to start of study treatment * May have a prior malignancy (other than the disease under study) the natural history or treatment of which is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * A 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
Exclusion criteria
* 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 * Participant has impairment of the gastrointestinal function that could affect absorption of capmatinib or is unable or unwilling to swallow tablets * 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 * Participant has uncontrolled tumor-related pain: Symptomatic lesions amenable to palliative radiotherapy (example, bone metastases, or metastases causing nerve impingement) should be treated more than 7 days prior to the administration of the first study treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants with Adverse events (AEs) by Severity | Up to 2 years 1 month | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs) | Cycle 1 (Day 1 through Day 28) | The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, hematologic toxicity, pulmonary toxicity, liver enzyme elevation, or treatment delay greater than (\>) 28 days due to unresolved toxicity. |
| Phase 2: Objective Response Rate | Up to 2 years 1 month | ORR is defined as the percentage of participants who achieve either a confirmed partial response (PR) or complete response (CR), using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants with AEs by Severity | Up to 2 years 1 month | An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the intervention. Severity will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters | Up to 2 years 1 month | Number of participants with abnormalities in clinical laboratory parameters (serum chemistry, hematology, coagulation, serology, and urinalysis) will be reported. |
| Phase 2: Duration of Response (DoR) | Up to 2 years 1 month | DoR is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death from any case, whichever comes first, for participants who have PR or CR. |
| Phase 2: Disease Control Rate (DCR) | Up to 2 years 1 month | DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1. |
| Phase 2: Progression Free Survival (PFS) | Up to 2 years 1 month | PFS is defined as the time from first dose date until the date of disease progression or death, whichever comes first, based on investigator assessment using RECIST version 1.1 |
| Phase 2: Overall Survival (OS) | Up to 2 years 1 month | OS is defined as the time from the date of administration of the first study treatment until the date of death due to any cause. |
| Phase 2: Time to Subsequent Therapy (TTST) | Up to 2 years 1 month | TTST is defined as the time from the date of administration of the first study treatment to the start date of the subsequent anticancer therapy following study treatment discontinuation, or death, whichever comes first. |
| Phase 2 (Cohort 1A): Change from Baseline in Health-related Quality of Life in (HRQoL) as Assessed by European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score | Baseline up to 2 years 1 month | EORTC-QLQ-C30 is a self-administered, 30-item questionnaire developed to assess the HRQoL of cancer participants. |
| Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score | Up to 2 years 1 month | NSCLC-SAQ assesses patient-reported symptom severity associated with NSCLC. |
| Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Score | Up to 2 years 1 month | EQ-5D-5L is a self-administered, standardized measure of health status. |
| Phase 2 (Cohort 1A): HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form Version 2.0 - Physical Function 8c (PROMIS PF 8c) Scale Score | Up to 2 years 1 month | PROMIS PF 8c is an 8-item fixed length short form derived from the PROMIS Physical Function item bank. It assesses activities of daily living, mobility, and global impact of physical functioning. |
Countries
Brazil, Canada, China, France, Germany, Italy, Japan, Poland, South Korea, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed