PolyDamas: A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer
Study Details
Study Description
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 by epidermal growth factor receptor (EGFR) exon19del or exon 21 leucine 858 to arginine substitution (L858R) mutations, who have progressed on or after prior standard of care therapy with a 3rd generation tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy, in the Phase 2 (expansion).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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). |
Drug: Cetrelimab
Cetrelimab will be administered as IV infusion.
Other Names:
Drug: Amivantamab
Amivantamab will be administered as IV infusion.
Other Names:
|
| Experimental: Phase 2 (Dose Expansion) Participants will receive amivantamab in combination with cetrelimab 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. |
Drug: Cetrelimab
Cetrelimab will be administered as IV infusion.
Other Names:
Drug: Amivantamab
Amivantamab will be administered as IV infusion.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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.
Secondary Outcome Measures
- 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.
- 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: 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 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.
Eligibility Criteria
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
-
Participant's tumor must have an epidermal growth factor receptor (EGFR) exon19del or exon 21 leucine 858 to arginine substitution (L858R) mutation
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Participant must have had disease progression on or after prior standard of care therapy with a 3rd generation EGFR TKI and after platinum-based chemotherapy
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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
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Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion Criteria:
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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
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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
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Has an active autoimmune disease or a documented history of autoimmune disease that requires systemic steroids or immunosuppressive agents
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Participant has received radiotherapy for palliative purposes less than 14 days prior to the first dose of study treatment
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Participant has a. (or has a history of) leptomeningeal disease (carcinomatous meningitis), b. spinal cord compression not definitively treated with surgery or radiation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Virginia Cancer Specialists | Fairfax | Virginia | United States | 22031 |
| 2 | Samsung Medical Center | Seoul | Korea, Republic of | 06351 | |
| 3 | University Malaya Medical Centre | Kuala Lumpur | Malaysia | 59100 | |
| 4 | Hospital Umum Sarawak | Kuching | Malaysia | 93586 |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CR109323
- 61186372PANSC2002