Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations (AMIGO-1)

September 25, 2025 updated by: Latin American Cooperative Oncology Group

A Single Arm, Phase 2 Study of Amivantamab, Lazertinib and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers (NSCLCs) With EGFR Mutations

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to test the hypothesis that delivery of maximum therapy consisting of lazertinib plus amivantamab plus chemotherapy as frontline treatment in patients with recurrent/metastatic NSCLC with EGFR exon 19 or exon 21 mutations will be feasible, safe, and will improve PFS compared to historical controls. If successful, this study may allow for the estimation of efficacy and toxicity of a three drug regimen of amivantamab, lazertinib, and pemetrexed and may support further evaluation of maximum therapy against osimertinib single agent, lazertinib single agent, osimertinib plus chemotherapy, and/or lazertinib plus amivantamab.

Study Type

Interventional

Enrollment (Actual)

54

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
      • Rio de Janeiro, Brazil, 20230-130
        • INCA - Instituto Nacional de Cancer
      • Rio de Janeiro, Brazil, 22250-905
        • Centro de Tratamento de Tumores Botafogo (Oncoclínicas)
      • São Paulo, Brazil, 01246-000
        • Icesp - Instituto Do Câncer Do Estado de São Paulo
      • São Paulo, Brazil, 01323-030
        • BP - A Beneficencia Portuguesa de São Paulo
      • São Paulo, Brazil, 04014-002
        • Sao Camilo Oncologia
    • Ceará
      • Fortaleza, Ceará, Brazil, 60810-180
        • Pronutrir - Oncologia e Nutrição
    • Espírito Santo
      • Cachoeiro de Itapemirim, Espírito Santo, Brazil, 29308-065
        • Hospital Evangelico de Cachoeiro de Itapemirim
    • Paraná
      • Curitiba, Paraná, Brazil, 81520-060
        • Hospital Erasto Gaertner
    • Rio Grande do Norte
      • Natal, Rio Grande do Norte, Brazil, 59062-000
        • Liga Norte Riograndense Contra o Câncer
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90050-170
        • Irmandade da Santa Casa de Misericordia de Porto Alegre
      • Porto Alegre, Rio Grande do Sul, Brazil, 91751-443
        • Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS
    • São Paulo
      • Barretos, São Paulo, Brazil, 14784400
        • Hospital de Amor de Barretos
      • Ribeirão Preto, São Paulo, Brazil, 14015-010
        • Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Hospital de Base de Sao Jose do Rio Preto

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Participant must be ≥18 years of age;
  2. Participant must have histologically or cytologically confirmed locally advanced or metastatic NSCLC not amenable to curative therapy. Participants must be treatment-naïve for metastatic NSCLC. Prior adjuvant and neo-adjuvant therapy for early-stage disease is permitted, prior systemic therapy for potentially curable locally advanced disease is also permitted;
  3. Participant must have a tumor that was previously determined to have Exon 19del or Exon 21 L858R substitution, as detected by a validated test in accordance with site standard of care. Note: A copy of the test report documenting the EGFR mutation must be included in the participant records and must also be submitted to the sponsor prior to enrollment;
  4. Unstained tumor tissue and blood (for ctDNA, biomarker), both collected prior to treatment initiation, must be provided. Unstained FFPE tumor tissue blocks must be provided whenever possible. Alternatively, re-cut unstained sections from FFPE tumor tissue block, presented on slides must be provided (recommended 10-15 slides);
  5. Subject must have specific organ and bone marrow function;
  6. Participant must have ECOG status of 0 to 2;
  7. Any toxicities from prior anticancer therapy must have resolved to CTCAE Grade 1 or baseline level;
  8. Participant must have at least 1 measurable lesion, according to RECIST v1.1 that has not been previously irradiated. Target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.

Exclusion Criteria:

  1. Participant has received any prior systemic treatment for metastatic disease (prior systemic therapy for potentially curable locally advanced disease, adjuvant or neoadjuvant therapy are allowed, if administered more than 12 months prior to the development of the recurrent disease);
  2. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to enrollment;
  3. Participant has severe co-morbidities that in the opinion of the investigator pose the patient at undue risk from participating in the study;
  4. Participant has an active or past medical history of leptomeningeal disease;
  5. Participant has spinal cord compression that has not been definitively treated with surgery or radiation or requires steroid treatment within 2 weeks prior to enrollment. Low-dose corticosteroid treatment ≤10mg/day prednisone or equivalent is allowed;
  6. Participant has an active or past medical history of Interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis;
  7. Immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment;
  8. Subject has uncontrolled inter-current illness;
  9. Participant has active cardiovascular disease;
  10. Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inhibitors or inducers and is unable to stop use for an appropriate washout period prior to enrollment (see Appendix 8: Prohibited and Restricted Medications and Therapies That Induce, Inhibit, or Are Substrates of CYP3A4/5);
  11. Participant has received any prior treatment with an EGFR TKI;
  12. Known positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg);
  13. Known positive hepatitis C antibody (anti-HCV). Note: Subjects with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible;
  14. Other clinically active or chronic liver disease;
  15. Known active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), Patients positive for human immunodeficiency virus (HIV) can be eligible if receiving highly active antiretroviral therapy (ART) and CD4 count >350 within 6 months of the start of treatment (consultation of Medical Monitor is required in this case). Screening for tuberculosis, hepatitis B, hepatitis C, and/or HIV infections is not required, unless there is clinical suspicion of these infections;
  16. Participant had major surgery (e.g., requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 2 weeks before signing the ICF, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: Amivantamab
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.
Drug: Lazertinib
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.
Drug: Pemetrexed 500 mg
Inhibits enzymes involved in folate-dependent metabolism, thereby disrupting cellular replication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the 18-month progression-free survival (PFS) rate
Time Frame: 18 months
To evaluate the 18-month progression-free survival (PFS) rate of amivantamab, lazertinib, carboplatin and pemetrexed for first-line treatment of recurrent / metastatic non-small cell lung cancers (NSCLCs) with EGFR mutations.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall progression-free survival
Time Frame: 18 months
18 months
Overall response rate
Time Frame: 18 months
Defined as the proportion of complete response (CR) or partial response (PR) according to RECIST v1.1.
18 months
Overall survival
Time Frame: 18 months
Overall survival is defined as the time from the date of enrollment to the date of participant's death due to any cause.
18 months
Progression-free survival After First Subsequent Therapy (PFS 2)
Time Frame: 18 months
The PFS 2 is defined as the time from enrollment until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.
18 months
Incidence of Treatment-Emergent Adverse Events and toxicity assessed by CTCAE v5.0
Time Frame: 18 months
Safety includes adverse events in terms of treatment-emergent adverse events (AE). The rate of any grade of adverse events as well as the rate of adverse events grade ≥3 according to the CTCAE version 5 will be evaluated. Adverse events of special interest of Amivantamab and Lazertinib will be based on the definitions given in the protocol of each one.
18 months
Performance status at progression-free survival 1 and progression-free survival 2
Time Frame: 18 months
18 months
Compliance
Time Frame: 18 months
Includes number of patients whose treatment had to be reduced, delayed, or permanently discontinued, grouped by reason. The reason for termination includes aspects of efficacy (e.g. termination due to tumor progression), safety (e.g. termination due to adverse events) and compliance (e.g. termination due to patient's withdrawal of consent).
18 months
Post-progression therapies
Time Frame: 18 months
Description of therapies after disease progression.
18 months
Patient reported outcomes
Time Frame: 18 months
Defined as the change from baseline of disease-related symptoms and quality of life based on European Organization for Research and Treatment of Cancer (EORTC) core cancer instrument and supplemental lung cancer module.
18 months
Intracranial Progression-Free Survival
Time Frame: 18 months
Intracranial PFS is defined as the time from enrollment until the date of objective intracranial disease progression or death, whichever comes first, using RECIST v1.1.
18 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Latin American Cooperative Oncology Group

Collaborators

Janssen, LP

Investigators

  • Principal Investigator: William Nassib William Junior, Latin American Cooperative Oncology Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2023

Primary Completion (Estimated)

January 30, 2026

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

February 25, 2022

First Submitted That Met QC Criteria

March 17, 2022

First Posted (Actual)

March 28, 2022

Study Record Updates

Last Update Posted (Estimated)

October 1, 2025

Last Update Submitted That Met QC Criteria

September 25, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LACOG 0821
  • 73841937LUC2002 (Other Grant/Funding Number: Janssen)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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