A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure

Conditions

• Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Lazertinib — DRUG
  Lazertinib will be administered orally.
• Amivantamab — DRUG
  Amivantamab will be administered as an IV infusion.
• Pemetrexed — DRUG
  Pemetrexed will be administered as an IV infusion.
• Carboplatin — DRUG
  Carboplatin will be administered as an IV infusion.

Study Details

The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.

Key Dates

Start date

Nov 17, 2021

Status verified

Jun 2026

Primary completion

Jul 10, 2023

Completion

Nov 30, 2027

Study Design

Enrollment

776 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Arm A: LACP/ACP-L
  LACP dosing (study start until 6 November 2022): Participants will receive Lazertinib orally along with Amivantamab, Pemetrexed, and Carboplatin as IV infusion starting on Cycle 1 Day 1 for 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression. ACP-L dosing (from 7 November 2022 until study completion): Participants will receive Amivantamab, Pemetrexed, and Carboplatin starting on Cycle 1 Day 1 for 4 cycles. Lazertinib in ACP-L will start on Cycle 5 Day 1 or sooner if carboplatin is discontinued before cycle 4 (each cycle consists of 21 days). Beginning with Cycle 5 Day 1, participants will receive Amivantamab, Pemetrexed and Lazertinib as maintenance until disease progression.
• Active Comparator: Arm B: CP (Carboplatin and Pemetrexed)
  Participants will receive Pemetrexed in combination with Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Pemetrexed as maintenance until disease progression.
• Experimental: Arm C: ACP (Amivantamab, Carboplatin and Pemetrexed)
  Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.
• Experimental: Arm A2 (Extension Cohort): ACP-L
  Participants will receive Amivantamab, Pemetrexed and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days), Lazertinib will start on C5D1 or sooner if carboplatin is discontinued earlier). After 4 cycles, participants will receive Pemetrexed, Amivantamab, Lazertinib as maintenance until disease progression.
• Experimental: Arm C2 (Extension Cohort): ACP
  Participants will receive Amivantamab, Pemetrexed, and Carboplatin as IV infusion for up to 4 cycles (each cycle consists of 21 days). After 4 cycles, participants will receive Amivantamab and Pemetrexed as maintenance until disease progression.

Primary Outcome Measure

Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months) ]

Locations (28)

Related coverage on Hipa.ai

• Amivantamab + Lazertinib + Chemo Improves PFS in EGFR+ NSCLC Post-Osimertinib
  Amivantamab · Apr 16, 2025 · ClinicalTrials.gov
• Amivantamab + Lazertinib Combo Doubles NSCLC PFS vs Chemo Alone
  Amivantamab · Jul 10, 2023 · ClinicalTrials.gov

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