A Phase 1/2 Study to Evaluate the Safety, Tolerability and PK of JIN-A02 in Patients With EGFR Mutant Advanced NSCLC

NCT05394831 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: JIN-A02
• Study Type: interventional
• Target: 150
• Locations: 3 countries
• Sites: 10

Brief Summary

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).

Conditions

EGFR Mutant Advanced Non-small Cell Lung Cancer

Keywords

4th generation EGFR inhibitors

Outcome Measures

Primary Outcomes (4)

• 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.

  28 days

• 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).

  28 days

• 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).

  28 days

• 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.

  21 days

Study Arms (1)

Phase 1 dose-escalation, Phase 1 dose-exploratory, Phase 2 dose-expansion

EXPERIMENTAL

Single arm

Drug: JIN-A02

Interventions

JIN-A02 DRUG

PO, QD

Phase 1 dose-escalation, Phase 1 dose-exploratory, Phase 2 dose-expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Part A dose escalation and Part B exploration studies: Advanced NSCLC subjects who are positive to EGFR mutant C797S or T790M
• Part C dose expansion study: Advanced NSCLC subjects who are positive for EGFR mutations C797S and T790M in Cohort 1, those who are positive for C797S and negative for T790M in Cohort 2, those who are negative for C797S and positive for T790M in Cohort 3, subjects who are positive for any EGFR mutations and stable brain metastasis in Cohort 4, and those who have any EGFR dependent mutations other than C797S or T790M in Cohort 5.
• For Part C, subjects with at least 1 measurable lesion that has not been previously radiated as defined by RECIST version 1.1
• Subjects with ECOG performance status 0 or 1
• Acute effect from a previous therapy that recovers to the baseline severity or ≤ Common Terminology Criteria for Adverse Events (CTCAE) grade 1, except for an AE not corresponding to a safety risk, as determined by the investigator based on discussion with the sponsor. Note: A chronic condition not expected to recover (≤ grade 2, e.g. neuropathy, myalgia, alopecia) is an exception, and a subject with such a condition can be enrolled.
• Appropriate bone marrow and organ functions, including the following:
• Hemoglobin ≥ 9.0 g/dL
• Platelet ≥ 75 × 109/L
• Absolute neutrophil count ≥ 1.0 × 109/L
• Serum Total Bilirubin (TBL) ≤ 1.5 × Upper Limit of Normal Range (ULN) (≤ 3.0 x ULN for a subject with documented Gilbert syndrome)
• Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3.0 ×ULN, or if there is a hepatic metastasis caused by tumor, ≤ 5.0 × ULN

You may not qualify if:

• 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
• \- Subjects requiring steroid escalation within 28 days before start of the study due to spinal cord compression with uncontrolled symptoms or Central Nervous System (CNS) metastasis or for CNS disease treatment; patients requiring local CNS disease treatment; and subjects with leptomeningeal disease. However, these subjects may be included in the study if they are systemically asymptomatic and stable 2 weeks after gamma knife therapy or 4 weeks after whole-brain irradiation
• For Part Part C: all Cohorts except for Cohort 4
• \- Subjects without CNS metastasis
• Subjects who received the following treatments:
• EGFR-TKI treatment within 7 days from the first dose of the investigational product
• Systemic anticancer treatment within 14 days or 5 half-lives (whichever is the shorter period) from the first dose of the investigational product
• Limited field radiation treatment within 7 days or extended field chest radiation treatment within 14 days from the first dose of the investigational product
• Immunotherapy or other antibody therapy within 28 days from the first dose of the investigational product
• Subjects who did not recover from a major surgery or side effects of such treatment, except for vascular access placement, within 28 days from the first dose of the investigational product as determined by the investigator \*A major surgery refers to a surgery on the abdomen, pelvis, cranium or intrapleural site or local site tissue and is defined as a procedure that may cause a risk to function or recovery of an organ and tissue based on the applicable site, subject's condition, and difficulty or duration of the surgery. A major surgery generally requires hospitalization of a varying period (often 1 week) and can be conducted by a surgical professional.
• Subjects with the following cardiac dysfunctions or clinically significant cardiac diseases:
• Corrected QT interval using Frederica formula (QTcF) \> 470 ms
• Cardiac arrhythmia that is clinically significant and uncontrolled (e.g. Type II second degree heart block or third degree heart block)
• Any factors increasing the risk of QTc prolongation or arrhythmia occurrence, such as hypokalemia, congenital long QT syndrome, family history of long QT syndrome, unexplained sudden death of a family member or direct family member at the age less than 40 years, or concomitant drugs known to prolong the QT interval or cause Torsades de Pointes

Sponsors & Collaborators

• J Ints Bio: lead

Study Sites (10)

Chao Family Comprehensive Cancer Center, University of California Irvine Healthcare

Orange, California, 92868, United States

ACTIVE NOT RECRUITING

National Cancer Center

Goyang-si, Gyeonggi-do, 03722, South Korea

RECRUITING

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

WITHDRAWN

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

The Catholic University, St. Mary's Hospital

Seoul, 06591, South Korea

NOT YET RECRUITING

Yonsei University Health System, Severance Hospital

Seoul, 10400, South Korea

RECRUITING

The Catholic University, St. Vincent's Hospital

Suwon, 16247, South Korea

RECRUITING

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Ratchathewi, Bangkok, 10400, Thailand

NOT YET RECRUITING

Study Officials

• Ethan Seah

  J Ints Bio

  STUDY DIRECTOR

Central Study Contacts

Gayeon Yeom

CONTACT

+821027126609; gayeon.yeom@jintsbio.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2022
• First Posted: May 27, 2022
• Study Start: July 30, 2023
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); KR (8); TH (1)