Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations (AMIGO-1)
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| ClinicalTrials.gov Identifier: NCT05299125 |
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Recruitment Status :
Recruiting
First Posted : March 28, 2022
Last Update Posted : October 24, 2023
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Sponsor:
Latin American Cooperative Oncology Group
Collaborator:
Janssen, LP
Information provided by (Responsible Party):
Latin American Cooperative Oncology Group
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Brief Summary:
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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Metastatic Non-small Cell Lung Cancers | Drug: Amivantamab Drug: Lazertinib Drug: Pemetrexed 500 mg | Phase 2 |
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 (Clinical Trial) |
| Estimated Enrollment : | 49 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | 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 |
| Actual Study Start Date : | May 24, 2023 |
| Estimated Primary Completion Date : | October 2026 |
| Estimated Study Completion Date : | April 2028 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Lung cancer
MedlinePlus related topics:
Lung Cancer
| Arm | Intervention/treatment |
|---|---|
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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 + (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 |
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. |
Primary Outcome Measures :
- 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.
Secondary Outcome Measures :
- Overall progression-free survival [ Time Frame: 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.
- 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.
- 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.
- 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.
- Performance status at progression-free survival 1 and progression-free survival 2 [ Time Frame: 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).
- Post-progression therapies [ Time Frame: 18 months ]Description of therapies after disease progression.
- 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.
- 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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Participant must be ≥18 years of age;
- 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;
- 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;
- 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);
- Subject must have specific organ and bone marrow function;
- Participant must have ECOG status of 0 to 2;
- Any toxicities from prior anticancer therapy must have resolved to CTCAE Grade 1 or baseline level;
- 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:
- 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);
- 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;
- Participant has severe co-morbidities that in the opinion of the investigator pose the patient at undue risk from participating in the study;
- Participant has an active or past medical history of leptomeningeal disease;
- 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;
- Participant has an active or past medical history of Interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis;
- Immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment;
- Subject has uncontrolled inter-current illness;
- Participant has active cardiovascular disease;
- 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);
- Participant has received any prior treatment with an EGFR TKI;
- Known positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg);
- 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;
- Other clinically active or chronic liver disease;
- 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;
- 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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05299125
Contacts
| Contact: Giana Corssac | +55 51 3384 5334 | giana.corssac@lacogcancerresearch.org | |
| Contact: Laura Voelcker | +55 51 3384 5334 | laura.voelcker@lacogcancerresearch.org |
Locations
| Brazil | |
| Pronutrir - Oncologia e Nutrição | Recruiting |
| Fortaleza, Ceará, Brazil, 60810-180 | |
| Contact: Tamizia Severo +55 85 99265-6791 tamizia@hotmail.com | |
| Principal Investigator: Eduardo Henrique Cronemberger Costa e Silva | |
| Hospital Evangélico de Cachoeiro de Itapemirim | Recruiting |
| Cachoeiro de Itapemirim, Espírito Santo, Brazil, 29308-065 | |
| Contact: Narelle de Jesus +55 28 3522-5095 narelle@iosc.com.br | |
| Principal Investigator: Sabina Bandeira Aleixo | |
| Hospital Erasto Gaertner | Not yet recruiting |
| Curitiba, Paraná, Brazil, 81520-060 | |
| Principal Investigator: Thais Abreu de Almeida | |
| Liga Norte Riograndense Contra o Câncer | Recruiting |
| Natal, Rio Grande Do Norte, Brazil, 59062-000 | |
| Contact: Janielle Ferreira +55 84 4009-5595 janielle.ferreira@liga.org.br | |
| Principal Investigator: Sulene Cunha Sousa Oliveira | |
| Irmandade da Santa Casa de Misericórdia de Porto Alegre | Recruiting |
| Porto Alegre, Rio Grande Do Sul, Brazil, 90050-170 | |
| Contact: Letícia Mariana +55 51 3213-7229 leticia.mariana@santacasa.org.br | |
| Principal Investigator: Manuela Zereu | |
| Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS | Recruiting |
| Porto Alegre, Rio Grande Do Sul, Brazil, 91751-443 | |
| Contact: Tasiana Simonetti +55 51 3320-3236 tasiana.simonetti@cpors.com | |
| Principal Investigator: Ana Caroline Zimmer Gelatti | |
| Hospital de Amor de Barretos | Recruiting |
| Barretos, São Paulo, Brazil, 14784400 | |
| Contact: Jéssica Frutuozo +55 11 3321-6637 jessica.frutuozo@hcancerbarretos.com.br | |
| Principal Investigator: Flávio Augusto Ferreira da Silva | |
| Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP | Recruiting |
| Ribeirão Preto, São Paulo, Brazil, 14015-010 | |
| Contact: Pamella Queluz +55 16 3963-6487 pamella.queluz@hcrp.usp.br | |
| Principal Investigator: Tatiane Cardoso Motta | |
| Hospital de Base de São José do Rio Preto | Recruiting |
| São José do Rio Preto, São Paulo, Brazil, 15090-000 | |
| Contact: Natália Gonzalez +55 17 3201-5054 natalia.gonzalez@centrodepesquisacip.com.br | |
| Principal Investigator: Káthia Cristina Abdalla | |
| INCA - Instituto Nacional de Câncer | Not yet recruiting |
| Rio de Janeiro, Brazil, 20230-130 | |
| Principal Investigator: Luiz Henrique de Lima Araújo | |
| Centro de Tratamento de Tumores Botafogo (Oncoclínicas) | Recruiting |
| Rio de Janeiro, Brazil, 22250-905 | |
| Contact: Thaiza Lombardo +55 11 2678-7474 thaiza.lombardo@oncoclinicas.com | |
| Principal Investigator: Pedro De Marchi | |
| ICESP - Instituto do Câncer do Estado de São Paulo | Recruiting |
| São Paulo, Brazil, 01246-000 | |
| Contact: Marlene Salgado +55 11 3893 2645 marlene.salgado@hc.fm.usp.br | |
| Principal Investigator: Gilberto de Castro Júnior | |
| BP - A Beneficência Portuguesa de São Paulo | Recruiting |
| São Paulo, Brazil, 01323-030 | |
| Contact: Ligia Silva +55 11 3505-6541 ligia.silva@bp.org.br | |
| Principal Investigator: William Nassib William Junior | |
| São Camilo Oncologia | Recruiting |
| São Paulo, Brazil, 04014-002 | |
| Contact: Daniele Bracale +55 11 4450-0366 daniele.bracale@hospitalsaocamilosp.org.br | |
| Principal Investigator: Felipe José Silva Melo Cruz | |
Sponsors and Collaborators
Latin American Cooperative Oncology Group
Janssen, LP
Investigators
| Principal Investigator: | William Nassib William Junior | Latin American Cooperative Oncology Group |
| Responsible Party: | Latin American Cooperative Oncology Group |
| ClinicalTrials.gov Identifier: | NCT05299125 |
| Other Study ID Numbers: |
LACOG 0821 73841937LUC2002 ( Other Grant/Funding Number: Janssen ) |
| First Posted: | March 28, 2022 Key Record Dates |
| Last Update Posted: | October 24, 2023 |
| Last Verified: | October 2023 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Lung Neoplasms Carcinoma, Non-Small-Cell Lung Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Carcinoma, Bronchogenic Bronchial Neoplasms |
Pemetrexed Amivantamab-vmjw Lazertinib Antineoplastic Agents Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Folic Acid Antagonists Nucleic Acid Synthesis Inhibitors Protein Kinase Inhibitors Antineoplastic Agents, Immunological |