Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations

Conditions

• Metastatic Non-small Cell Lung Cancers

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Amivantamab — DRUG
  Low fucose, fully human immunoglobulin gamma-1-based bispecific antibody directed against EGFR and MET tyrosine kinase receptors. It shows clinical activity against tumors with the primary activating EGFR mutations Exon 19del or Exon 21 L858R substitution, EGFR Exon 20ins mutations, the EGFR resistance mutations Threonine790Methionine (T790M) or Cysteine797Serine (C797S), and activation of the Mesenchymal Epithelial Transition (MET) pathway.
• Lazertinib — DRUG
  It selectively inhibits both primary activating EGFR mutations (Exon 19del, Exon 21 L858R substitution) and the EGFR T790M resistance mutation, while having less activity versus wild-type EGFR.
• Pemetrexed 500 mg — DRUG
  Inhibits enzymes involved in folate-dependent metabolism, thereby disrupting cellular replication.

Study Details

This is a phase II, single-arm, multicenter trial, conducted through Latin American Coorperative Oncology Group (LACOG). Treatment-naïve patients with recurrent/metastatic NSCLCs harboring EGFR exon 19 deletions or exon 21 L858R point mutations will be enrolled. At baseline, an archival or (optional) new tissue sample will be obtained for biomarker evaluation, as well as liquid biopsies. Treatment will continue until disease progression or unacceptable toxicity.

Key Dates

Start date

May 24, 2023

Status verified

Sep 2025

Primary completion

Jan 30, 2026

Completion

Jul 31, 2027

Study Design

Enrollment

54 participants (actual)

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Single Arm: Therapy consisting of lazertinib plus amivantamab plus chemotherapy
  CYCLE 1 (21-day cycle) Amivantamab 1400 mg (1750 mg if body weight is \>80 kg) IV once weekly + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1 CYCLE 2 (21-day cycle) Amivantamab 1400 mg (1750 mg if body weight is \>80 kg) IV on day 1 + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1 MAINTENANCE CYCLES 3 - 8 (21-day cycle) Amivantamab 1750 mg (2100 mg if body weight is \>80 kg) IV on day 1 + Lazertinib 240 mg po daily + Pemetrexed 500 mg/m² IV on day 1 MAINTENANCE CYCLES 9 + (21-day cycle) Amivantamab 1750 mg (2100 mg if body weight is \>80 kg) IV on day 1 + Lazertinib 240 mg po daily

Primary Outcome Measure

To evaluate the 18-month progression-free survival (PFS) rate [ Time Frame: 18 months ]