Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The purpose of this study is to identify the recommended Phase 2 (combination) dose (RP2CD) of the amivantamab and cetrelimab 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 combination at the selected RP2CD in participants with NSCLC characterized on the basis of epidermal growth factor receptor (EGFR) and Programmed-cell death Ligand (PD-L)1 status, in the Phase 2 (expansion).
Interventions
DRUGCetrelimab
Cetrelimab will be administered as IV infusion.
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
* 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 * 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 * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Participant has an 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 * 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 agents * Participant has received radiotherapy for palliative purposes less than 14 days prior to the first dose of study treatment * Participant has a. (or has a history of) leptomeningeal disease (carcinomatous meningitis), b. spinal cord compression not definitively treated with surgery or radiation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs) | Up to 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, hematological toxicity, pulmonary toxicity, liver enzyme elevation, treatment delay greater than (\>) 28 days due to unresolved toxicity, or immune-related toxicity requiring the use of therapies in excess of corticosteroids. |
| Phase 2: Objective Response Rate | Up to 2 years 3 months | 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 as per investigator assessment. |
| Phase 1: Number of Participants with Adverse events (AEs) by Severity | Up to 2 years 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1 and Phase 2: Number of Participants with Abnormalities in Clinical Laboratory Parameters | Up to 2 years 3 months | 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 3 months | 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. If a participant does not progress following a response, then his/her duration of response will be censored at the date of last evaluable disease assessment. Participants who started a subsequent anticancer therapy in the absence of progression will be censored at the last disease assessment before or on the start of subsequent therapy. |
| Phase 2: Disease Control Rate (DCR) | Up to 2 years 3 months | DCR is defined as the percentage of participants who achieve a PR, CR, or stable disease using RECIST version 1.1 by investigator review. |
| Phase 2: Overall Survival (OS) | Up to 2 years 3 months | 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. Any participant not known to have died at the time of analysis will be censored based on the last recorded date on which the participant was known to be alive. |
| Phase 2: Progression Free Survival (PFS) | Up to 2 years 3 months | 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. Participants who have not progressed or have not died at the time of analysis will be censored at the time of their last evaluable RECIST v1.1 assessment. |
| Phase 1 and Phase 2: Number of Participants with AEs by Severity | Up to 2 years 3 months | 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. |
Countries
Brazil, Italy, Malaysia, 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