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).
Brief Title
A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Carcinoma, Non-Small-Cell Lung
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05488314
Org Class
Industry
Org Full Name
Janssen Research & Development, LLC
Org Study Id
CR109260
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer
Primary Outcomes
Outcome Description
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.
Outcome Measure
Phase 1: Number of Participants with Adverse events (AEs) by Severity
Outcome Time Frame
Up to 2 years 1 month
Outcome Description
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.
Outcome Measure
Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Outcome Time Frame
Cycle 1 (Day 1 through Day 28)
Outcome Description
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.
Outcome Measure
Phase 2: Objective Response Rate
Outcome Time Frame
Up to 2 years 1 month
Secondary Ids
Secondary Id
61186372PANSC2001
Secondary Id
2022-000485-18
Secondary Id
2023-508256-19-00
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 1: Number of Participants with AEs by Severity
Outcome Description
Number of participants with abnormalities in clinical laboratory parameters (serum chemistry, hematology, coagulation, serology, and urinalysis) will be reported.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 1: Number of Participants with Abnormalities in Clinical Laboratory Parameters
Outcome Description
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.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2: Duration of Response (DoR)
Outcome Description
DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2: Disease Control Rate (DCR)
Outcome Description
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
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2: Progression Free Survival (PFS)
Outcome Description
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.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2: Overall Survival (OS)
Outcome Description
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.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2: Time to Subsequent Therapy (TTST)
Outcome Description
EORTC-QLQ-C30 is a self-administered, 30-item questionnaire developed to assess the HRQoL of cancer participants.
Outcome Time Frame
Baseline up to 2 years 1 month
Outcome Measure
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
Outcome Description
NSCLC-SAQ assesses patient-reported symptom severity associated with NSCLC.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2 (Cohort 1A): HRQoL as Assessed by Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ) Scale Score
Outcome Description
EQ-5D-5L is a self-administered, standardized measure of health status.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
Phase 2 (Cohort 1A): HRQoL as Assessed by EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Score
Outcome Description
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.
Outcome Time Frame
Up to 2 years 1 month
Outcome Measure
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
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org