A Phase 1/2 Study to Evaluate the Safety, Tolerability and PK of JIN-A02 in Patients With EGFR Mutant Advanced NSCLC
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorJ Ints Bio
About this trial
This study is a Phase I/II open-label, multi-center study to evaluate the safety, tolerability, PK, and an anti-tumor activity of JIN-A02, a 4th generation EGFR-TKI agent for oral administration, in EGFR mutant-positive, advanced NSCLC subjects who showed disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy and/or no more than a single platinum-based anticancer chemotherapy. In Part A of the study, dose escalation is carried out where MTD is evaluated using Bayesian Optimal Interval (BOIN) design in subjects with advanced NSCLC harboring EGFR-mutation of C797S or T790M. In Part B, dose exploration is carried out to further evaluate the safety of JIN-A02 and to determine the RP2D using 2 preliminary effective dose levels and with the help of a safety review committee (SRC) in advanced NSCLC subjects harboring EGFR mutant C797S or T790M. In Part C dose expansion study, subjects with EGFR mutant who show disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapy with activity against T790M such as Osimertinib and/or no more than one platinum-based anticancer chemotherapy, are divided into 5 different cohorts based on the EGFR mutation and the anti-tumor activity of JIN-A02 is evaluated. Before enrollment in the study, the EGFR mutant profile is determined using either tumor tissue and/or plasma ctDNA. The profile is determined locally through a test method approved by the sponsor. The sponsor reviews and approves each potential subject for enrollment. Study eligibility evaluation will utilize local test(s).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Subjects age 18 or above (19 or above for South Korea)
Subjects with pathologically confirmed and finally diagnosed advanced and/or metastatic NSCLC with active EGFR mutant
Subjects who show disease progression after receiving standard anticancer therapy, including approved EGFR-TKI therapeutic and/or up to 1 time of platinum-based anticancer chemotherapy. For the Part C dose expansion phase, approved EGFR-TKI with activity against T790M mutant such as Osimertinib must be included.
Subjects with a test result of locally confirmed EGFR mutant obtained through a test method approved by the sponsor using either a tumor tissue and/or plasma ctDNA. It is preferred that samples used for analysis are collected during or after disease progression from the last EGFR-TKI administration. If there is a sample retained after disease progression from prior therapy, it may be submitted.
Disqualifiers
NSCLC with mixed squamous cell histology and tumor with histological transformation (presence of transition from NSCLC to SCLC and epithelial mesenchymal transition)
For Part A, B, and Cohort 4 of Part C
For Part Part C: all Cohorts except for Cohort 4
EGFR-TKI treatment within 7 days from the first dose of the investigational product
Trial design
Design model
Sequential
Treatments tested in this trial
JIN-A02
DrugPO, QD
Treatment groups
150 Participants
are divided into 1 treatment groupGroup A: Phase 1 dose-escalation, Phase 1 dose-exploratory, Phase 2 dose-expansionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Maximum Tolerable Dose (MTD)
In the Part A dose escalation study, MTD is evaluated in DLT Set. When the study ends according to the BOIN design, the DLT rate per dose level is estimated as posterior probability based on the beta-binomial model and 95% CI is presented. The dose level at which the estimated DLT rate is closest to the target toxicity rate 0.3 is selected as MTD. If two or more dose levels are selected at a rate lower than 0.3, a higher one is selected as MTD. If two or more dose levels are selected at a rate higher than 0.3, a lower one is selected as MTD.
Time frame
28 days2
Adverse Events (AE) rate
Safety evaluation is analyzed based on the Safety Set. Safety is clinically evaluated by assessing all relevant endpoints, including AE, SAE, laboratory tests, vital signs, ECG results and concomitant drugs. Reported AE terminologies are standardized using MedDRA and the AE grade and intensity are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The AE summary focuses on AE that first occurred after initial administration of IP or that occurred after administration as an aggravation of pre-existing symptoms. AEs are summarized by the number and percentage of subjects experiencing AE per cohort based on the System Organ Class (SOC) and Preferred Term (PT).
Time frame
28 days3
Serious Adverse Events (SAE) rate
Safety evaluation is analyzed based on the Safety Set. Safety is clinically evaluated by assessing all relevant endpoints, including AE, SAE, laboratory tests, vital signs, ECG results and concomitant drugs. Reported AE terminologies are standardized using MedDRA and the AE grade and intensity are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The AE summary focuses on AE that first occurred after initial administration of IP or that occurred after administration as an aggravation of pre-existing symptoms. AEs are summarized by the number and percentage of subjects experiencing AE per cohort based on the System Organ Class (SOC) and Preferred Term (PT).
Time frame
28 days4
Dose Limiting Toxicity (DLT)
DLT is evaluated for all subjects enrolled to cycle 1 (DLT evaluation period: 21 days) of the Part A dose escalation study. When a subject receives at least 75% of his or her assigned daily dose during the DLT period or shows DLT, the subject is considered evaluable for DLT. All AEs that occur during the DLT period, are possibly related to JIN-A02 in the least and satisfy all of the following criteria are designated as DLT. Also, the occurrence of any of the toxicities outlined in this section will be considered a DLT unless clearly related to underlying disease or extraneous causes.
Time frame
21 days Source ClinicalTrials.gov