JIN-A02 Plus Amivantamab in EGFR-Mutant NSCLC After Third-Generation EGFR-TKI Failure
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age19+
SponsorYonsei University
About this trial
This Phase 1 study will evaluate the safety, maximum tolerated dose, recommended Phase 2 dose, and preliminary antitumor activity of JIN-A02 in combination with amivantamab in participants with advanced EGFR-mutant non-small cell lung cancer whose disease has progressed after treatment with a third-generation EGFR tyrosine kinase inhibitor.
The study includes a dose-escalation phase and a dose-expansion phase. During dose escalation, participants will receive oral JIN-A02 once daily at planned dose levels of 120 mg, 160 mg, or 200 mg in combination with weight-based intravenous amivantamab. Dose escalation will follow a Bayesian optimal interval design, and dose-limiting toxicities during the first 28-day treatment cycle will be used to determine the maximum tolerated dose and recommended Phase 2 dose.
After the recommended Phase 2 dose is determined, additional participants will be enrolled in the dose-expansion phase to further evaluate safety and preliminary antitumor activity. Efficacy assessments will include objective response rate and progression-free survival according to RECIST version 1.1. Exploratory analyses may evaluate changes in EGFR mutations and resistance-associated genomic alterations using circulating tumor DNA collected before and during treatment and at the end of treatment.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects aged 19 years or older.
Subjects with advanced and/or metastatic NSCLC harboring an activating EGFR mutation (Ex19del or L858R), as confirmed by testing of tissue or blood samples, whose disease has progressed following treatment with a third-generation EGFR-TKI, such as osimertinib or lazertinib. Subjects who received platinum-based chemotherapy after EGFR-TKI treatment may have received no more than one such regimen.
Subjects with at least one measurable lesion according to RECIST v1.1.
Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Disqualifiers
Subjects with NSCLC histologically diagnosed as having a mixed squamous cell component or with histologic transformation, including transformation from NSCLC to small cell lung cancer (SCLC) or the presence of epithelial-to-mesenchymal transition.
Subjects with uncontrolled symptomatic spinal cord compression or central nervous system (CNS) metastases; subjects requiring an increase in corticosteroid dose within 28 days before study initiation for the treatment of CNS disease; subjects requiring local treatment for CNS disease; or subjects with leptomeningeal disease. However, subjects whose condition remains stable or who are systemically asymptomatic at least 2 weeks after gamma knife treatment or at least 4 weeks after whole-brain irradiation may be eligible to participate in the study.
EGFR-TKI therapy or systemic anticancer therapy within 14 days or 5 half-lives, whichever is longer, before the first dose of the investigational product, or any prior treatment with a fourth-generation EGFR-TKI.
Limited-field radiotherapy within 7 days or extended-field thoracic radiotherapy within 14 days before the first dose of the investigational product.
Trial design
Design model
Single group
Treatments tested in this trial
JIN-A02 in Combination with Amivantamab
DrugParticipants will receive oral JIN-A02 once daily in continuous 28-day treatment cycles in combination with intravenous amivantamab. During dose escalation, the planned JIN-A02 dose levels are 120 mg, 160 mg, and 200 mg once daily. Amivantamab will be administered at 1,050 mg for participants with a baseline body weight of less than 80 kg or 1,400 mg for participants weighing 80 kg or more. The first amivantamab dose will be split between Cycle 1 Days 1 and 2, followed by administration on Days 8, 15, and 22 of Cycle 1 and every 2 weeks from Cycle 2 onward. On combination-treatment days, JIN-A02 will be administered within approximately 15 minutes before amivantamab.
Treatment groups
36 Participants
are divided into 1 treatment groupGroup A: JIN-A02 Plus AmivantamabExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Incidence of Dose-Limiting Toxicities
The incidence of dose-limiting toxicities will be evaluated during the first 28-day treatment cycle. Dose-limiting toxicities will be defined and graded according to the criteria specified in the protocol.
Time frame
During Cycle 1, up to 28 days after the first dose2
Maximum Tolerated Dose of JIN-A02 in Combination With Amivantamab
The maximum tolerated dose will be determined based on dose-limiting toxicities observed during Cycle 1 and dose-escalation decisions made according to the Bayesian optimal interval design.
Time frame
Through completion of the dose-escalation phase, approximately 8 months3
Recommended Phase 2 Dose of JIN-A02 in Combination With Amivantamab
The recommended Phase 2 dose will be determined based on the totality of available safety, tolerability, pharmacokinetic, and preliminary antitumor activity data from the dose-escalation phase.
Time frame
Through completion of the dose-escalation phase, approximately 8 monthsSecondary outcomes
1
Objective Response Rate According to RECIST Version 1.1
Objective response rate is defined as the proportion of participants with a confirmed best overall response of complete response or partial response according to RECIST version 1.1. Tumor assessments will be performed at baseline, every 8 weeks from Cycle 3 Day 1 through 1 year after the first dose, and every 12 weeks thereafter until disease progression. For participants with long-term stable disease, assessments may be performed every 16 weeks.
Time frame
From baseline until documented disease progression, up to approximately 2 years2
Progression-Free Survival According to RECIST Version 1.1
Progression-free survival is defined as the time from the first dose of study treatment to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first. Participants without documented disease progression at the End-of-Treatment visit will continue progression-free survival follow-up every 12 weeks.
Time frame
From the first dose until documented disease progression or death from any cause, whichever occurs first, up to approximately 2 years3
Incidence of Treatment-Emergent Adverse Events
Safety and tolerability will be assessed based on the incidence, severity, seriousness, and relationship to study treatment of treatment-emergent adverse events and serious adverse events. Safety assessments will also include clinical laboratory tests, vital signs, physical examinations, 12-lead electrocardiograms, and other protocol-specified evaluations.
Time frame
From the first dose through 30 days after the last doseLocations
Sponsors and contacts
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Source ClinicalTrials.gov
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