A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas)

• ClinicalTrials.gov Identifier: NCT05908734
• Recruitment Status: Recruiting
• First Posted: June 18, 2023
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: June 6, 2023
• First Posted Date: June 18, 2023
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: May 18, 2023
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2023)

• Phase 1: Number of Participants with Adverse events (AEs) by Severity [ Time Frame: 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.
• Phase 1: Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: 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 [ Time Frame: 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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 16, 2023)

• Phase 1 and Phase 2: Number of Participants with AEs by Severity [ Time Frame: 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.
• Phase 1 and Phase 2: Number of Participants with Abnormalities in Clinical Laboratory Parameters [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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: Progression Free Survival (PFS) [ Time Frame: 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 2: Overall Survival (OS) [ Time Frame: 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer
• Official Title: A Phase 1/2 Study Evaluating the Safety and Efficacy of Amivantamab and Cetrelimab Combination Therapy in Metastatic Non-small Cell Lung Cancer
• 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Cetrelimab
  Cetrelimab will be administered as IV infusion.
  Other Name: JNJ-63723283
• Drug: Amivantamab
  Amivantamab will be administered as IV infusion.
  Other Name: JNJ-61186372

Study Arms

• Experimental: Phase 1 (Combination Dose Selection)
  Participants will receive amivantamab low dose or high dose intravenous (IV) infusion based on body weight from Cycle 1 Day 1, Day 2, and subsequently Day 8, Day 15, and Day 22 and then every 2 weeks from Cycle 2 in combination with cetrelimab IV infusion from Cycle 1 Day 2 (after the Day 2 infusion of amivantamab). Doses will be escalated or de-escalated based on the dose limiting toxicities (DLTs) and the recommended Phase 2 combination dose (RP2CD) will be determined by the study evaluation team (SET).
  Interventions:

  • Drug: Cetrelimab
  • Drug: Amivantamab
• Experimental: Phase 2 (Dose Expansion)
  Participants will receive amivantamab in combination with cetrelimab in Cohorts A and B at the RP2CD determined by the SET in Phase 1. Participants will continue study treatment until disease progression, unacceptable toxicity, or until another criterion for discontinuation of study treatment is met.
  Interventions:

  • Drug: Cetrelimab
  • Drug: Amivantamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 18, 2023): 80
• Original Estimated Enrollment (submitted: June 16, 2023): 20
• Estimated Study Completion Date: August 22, 2026
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Korea, Republic of, Malaysia, Turkey, United States

Administrative Information

• NCT Number: NCT05908734
• Other Study ID Numbers: CR109323; 61186372PANSC2002 ( Other Identifier: Janssen Research & Development, LLC ); 2022-501452-29-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024