Clinical trial NCT05299125: Amivantamab, Lazertinib, and Pemetrexed for First-line Treatment of Recurrent/Metastatic Non-small Cell Lung Cancers With Epidermal Growth Factor Receptor Mutations
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Non-small Cell Lung Cancers
Lead sponsor: Latin American Cooperative Oncology Group
Sponsor class: OTHER
Collaborators: name: Janssen, LP
First posted: 2022-03-28
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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 \&gt;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.

Primary outcomes:
measure: To evaluate the 18-month progression-free survival (PFS) rate
timeFrame: 18 months
Secondary outcomes:
measure: Overall progression-free survival
timeFrame: 18 months
measure: Overall response rate
timeFrame: 18 months
measure: Overall survival
timeFrame: 18 months
measure: Progression-free survival After First Subsequent Therapy (PFS 2)
timeFrame: 18 months
measure: Incidence of Treatment-Emergent Adverse Events and toxicity assessed by CTCAE v5.0
timeFrame: 18 months
measure: Performance status at progression-free survival 1 and progression-free survival 2
timeFrame: 18 months
measure: Compliance
timeFrame: 18 months
measure: Post-progression therapies
timeFrame: 18 months
measure: Patient reported outcomes
timeFrame: 18 months
measure: Intracranial Progression-Free Survival
timeFrame: 18 months
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Pronutrir - Oncologia e Nutrição
state: Ceará
city: Cachoeiro de Itapemirim
country: Brazil
facility: Hospital Evangélico de Cachoeiro de Itapemirim
state: Espírito Santo
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra o Câncer
state: Rio Grande Do Norte
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericórdia de Porto Alegre
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Centro de Pesquisa em Oncologia do Hospital São Lucas da PUCRS
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Amor de Barretos
state: São Paulo
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto - USP
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de São José do Rio Preto
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: INCA - Instituto Nacional de Câncer
city: Rio de Janeiro
country: Brazil
facility: Centro de Tratamento de Tumores Botafogo (Oncoclínicas)
city: São Paulo
country: Brazil
facility: ICESP - Instituto do Câncer do Estado de São Paulo
city: São Paulo
country: Brazil
facility: BP - A Beneficência Portuguesa de São Paulo
city: São Paulo
country: Brazil
facility: São Camilo Oncologia
Study officials:
affiliation: Latin American Cooperative Oncology Group
name: William Nassib William Junior
role: PRINCIPAL_INVESTIGATOR
References: