Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer

Conditions

• Non-Small-Cell Lung Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Amivantamab — DRUG
  The first cohort of participants will receive IV infusions of Amivantamab 140 mg as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level until maximum tolerated dose is reached or all planned doses are administered. Participants will receive lazertinib and Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. The duration of each treatment cycle is 28 days. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with the administration of standard of care carboplatin and pemetrexed.
• Amivantamab — DRUG
  Participants will receive IV infusion of Amivantamab as monotherapy at RP2D regimen or in combination lazertinib at RP2CD regimen as determined in Part 1.
• Lazertinib — DRUG
  Lazertinib will be administered in combination with Amivantamab at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily on the 28-day Amivantamab treatment cycle.
• Carboplatin — DRUG
  Participants will receive carboplatin in combination with pemetrexed and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.
• Pemetrexed — DRUG
  Participants will receive pemetrexed in combination with carboplatin and Amivantamab as an IV infusion on 21-day treatment cycle in Part 1 Chemotherapy Combination Cohort only.

Study Details

The purpose of study is to evaluate the safety, pharmacokinetics, and preliminary efficacy of Amivantamab as a monotherapy and in combination with lazertinib, and to determine the recommended Phase 2 dose (RP2D) (monotherapy), recommended Phase 2 combination dose (RP2CD) (combination therapy), and to determine recommended Phase 2 Dose (RP2q3W) with combination chemotherapy (Amivantamab in combination with standard of care carboplatin and pemetrexed) in 21 day treatment cycle for participants with advanced non-small cell lung cancer (NSCLC).

Key Dates

Start date

May 24, 2016

Status verified

Jun 2026

Primary completion

Dec 31, 2026

Completion

Dec 31, 2026

Study Design

Enrollment

751 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Part 1:Amivantamab Monotherapy+Combination Dose Escalations
  The first cohort of participants will receive intravenous (IV) infusions of Amivantamab 140 milligram (mg) as monotherapy. Each subsequent cohort will receive IV infusions of Amivantamab at increased dose level. Dose escalation will continue until maximum tolerated dose is reached or all planned doses are administered. Participants will receive IV infusion of Amivantamab once weekly during cycle 1 and once every 2 weeks during subsequent cycles (duration of each treatment cycle is 28 days). Participants will receive lazertinib and Amivantamab on Cycle 1 Day 1 (C1D1) prior to initiation of Amivantamab (C1D1) at predefined dose levels, based upon observed safety and protocol defined criteria. Lazertinib will be administered daily thereafter, on 28-day Amivantamab treatment cycle. In Chemotherapy Combination Cohort, participants will receive Amivantamab, administered on a 21-day cycle, in combination with standard of care carboplatin and pemetrexed.
• Experimental: Part 2:Amivantamab Monotherapy+Combination Dose Expansion
  Participants will receive IV infusion of Amivantamab as monotherapy at Phase 2 dose (RP2D) regimen or in combination lazertinib at the recommended Phase 2 combination dose (RP2CD) regimen as determined in Part 1. The purpose of dose expansion is to further evaluate safety, tolerability, pharmacokinetic, and to assess preliminary efficacy in monotherapy and combination therapy cohorts.

Primary Outcome Measure

Part 1: Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: Up to Day 28 ]

Locations (17)

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