A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions

Phase 3

Active, not recruiting

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: Carboplatin
Drug: Amivantamab
Drug: Pemetrexed

Registration Number: NCT04538664

Lead Sponsor: Janssen Research & Development, LLC

Brief Summary: The purpose of this study is to compare the efficacy, as demonstrated by progression-free survival (PFS), in participants treated with amivantamab in combination with chemotherapy, versus chemotherapy alone in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) characterized by EGFR Exon 20ins mutations.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 308

Inclusion Criteria

Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous non-small cell lung cancer (NSCLC) with documented primary epidermal growth factor receptor (EGFR) Exon 20ins activating mutation
Participant must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Participant must agree to genetic characterization of tumor status through the required pretreatment tumor biopsy (or submission of equivalent archival material), as well as baseline and periodic blood samples for analysis of tumor mutations in the bloodstream
A female participant of childbearing potential must have a negative serum or urine 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

Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance)
Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible)
Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation
Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD, or radiation pneumonitis
Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local prescribing information for each agent). Participant has a history of hypersensitivity to, or cannot take, vitamin B12 or folic acid

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm B: Chemotherapy Alone	Carboplatin	Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
Arm A: Amivantamab + Chemotherapy	Carboplatin	Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
Arm A: Amivantamab + Chemotherapy	Pemetrexed	Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
Arm B: Chemotherapy Alone	Pemetrexed	Participants will receive pemetrexed 500 mg/m\^2 IV infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin AUC 5 IV infusion will be administered on Day 1 of each 21-day cycle for up to 4 cycles. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will either continue to receive the chemotherapy or cross over to amivantamab in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.
Arm A: Amivantamab + Chemotherapy	Amivantamab	Participants will receive pemetrexed 500 milligram per meter square (mg/m\^2) intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression. Carboplatin area under the concentration-time curve 5 milligram per milliliter (mg/mL) per minute (AUC 5) will be administered as IV infusion on Day 1 of each 21 day cycle, for up to 4 cycles. Participants will receive amivantamab 1400 mg (1750 mg if body weight is \>=80 kilogram \[kg\]) by IV infusion once weekly up to Cycle 2 Day 1, then 1750 mg (2100 mg if body weight is \>=80 kg) on Day 1 of each 21-day cycle, starting with Cycle 3. Following the primary analysis for efficacy, the study will transition to an OLE phase and participants will continue to receive the amivantamab plus chemotherapy in OLE phase. Participants who completed OLE period will enter LTE period and continue to receive same treatment.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)	From randomization to either disease progression or death whichever occurs first (up to 29 months)	PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) in the absence of progression, whichever came first. Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment. Pharmacodynamic: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).

Secondary Outcome Measures

Name	Time	Method
Overall Survival (OS)	Up to 5 years 3 months
Duration of Response (DoR)	Up to 5 years 3 months
Time to Symptomatic Progression (TTSP)	Up to 5 years 3 months
Objective Response Rate (ORR)	Up to 5 years 3 months
Number of Participants Treatment-emergent Adverse Events (TEAEs)	From Day 1 to 5 years 2 months
Serum Concentration of Amivantamab	Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Progression-Free Survival After First Subsequent Therapy (PFS2)	Up to 5 years 3 months
Number of Participants With Clinical Laboratory Abnormalities	Up to 5 years 3 months
Number of Participants With Vital Signs Abnormalities	Up to 5 years 3 months
Time to Subsequent Therapy (TST)	Up to 5 years 3 months
Number of Participants TEAEs With Severity	From Day 1 to 5 years 2 months
Number of Participants With Anti-Amivantamab Antibodies	Day 1 (Cycles 1, 2, 3, 5, 7, 9, 11, 13), Day 2 (Cycle 1)
Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)	From baseline to 5 years 3 months
Change From Baseline in Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF)	From baseline to 5 years 3 months
Number of Participants With Physical Examination Abnormalities	Up to 5 years 3 months

Trial Locations

Locations (228): Sir Run Run Shaw Hospital Zhejiang University School of Medicine
🇨🇳
Hangzhou, China
Centrum Onkologii im Prof F Lukaszczyka
🇵🇱
Bydgoszcz, Poland
City of Hope
🇺🇸
Duarte, California, United States
University of California Irvine
🇺🇸
Orange, California, United States
UCLA
🇺🇸
Santa Monica, California, United States
Georgetown University Hospital
🇺🇸
Washington, District of Columbia, United States
H. Lee Moffitt Cancer & Research Institute
🇺🇸
Tampa, Florida, United States
University Cancer And Blood Center LLC
🇺🇸
Athens, Georgia, United States
Henry Ford Hospital
🇺🇸
Detroit, Michigan, United States
Washington University Medical Center
🇺🇸
Saint Louis, Missouri, United States
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Sir Run Run Shaw Hospital Zhejiang University School of Medicine
🇨🇳Hangzhou, China