JIN-A02 for Non-Small Cell Lung Cancer

Recruiting at 9 trial locations

Overseen By Gayeon Yeom

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: J Ints Bio

Must be taking: EGFR-TKI

Must not be taking: Steroids, Immunotherapy

Disqualifiers: Mixed squamous cell, Cardiac dysfunctions, Active infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

150 Participants Needed

Trial Summary

What is the purpose of 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).

Will I have to stop taking my current medications?

The trial requires that participants stop taking certain medications before starting the study. Specifically, you must stop EGFR-TKI treatment at least 7 days before the first dose of the trial drug and any systemic anticancer treatment within 14 days or 5 half-lives, whichever is shorter. Other treatments like immunotherapy must be stopped 28 days before the trial.

What data supports the effectiveness of the treatment JIN-A02 for non-small cell lung cancer?

Research on similar traditional Chinese formulas, like Jinfu'an Decoction, shows they can help treat lung cancer by slowing down tumor growth and reducing the spread of cancer cells. These formulas have been used to improve the quality of life and survival in patients with non-small cell lung cancer. ^{1 2 3 4 5}

Research Team

Ethan Seah

Principal Investigator

J Ints Bio

Eligibility Criteria

Adults with advanced non-small cell lung cancer (NSCLC) that has specific EGFR mutations and worsened after standard treatments, including certain drugs or chemotherapy. They must be generally healthy, able to take oral medication, and have at least one measurable tumor lesion. Women of childbearing age and sexually active men must use effective contraception.

Inclusion Criteria

If you had side effects from a previous treatment, they should have either gone back to how they were before or be very mild, unless the side effect doesn't pose a safety risk. If you have a long-term condition from the previous treatment that is not expected to get much better, you can still join the trial.

My advanced lung cancer has an active EGFR mutation.

I am a man who will use birth control and not donate sperm.

Exclusion Criteria

My cancer has not spread to my brain.

I need more steroids for my spinal or brain condition before joining the study.

Subjects who received specific treatments within defined periods from the first dose of the investigational product

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Part A of the study evaluates the Maximum Tolerable Dose (MTD) using the BOIN design in advanced or metastatic NSCLC subjects with EGFR mutant C797S or T790M.

28 days per cycle

Regular visits for dose evaluation and safety monitoring

Dose Exploration

Part B of the study determines the optimal RP2D by further investigating safety, tolerability, PK, and efficacy of JIN-A02.

Varies based on dose level

Regular visits for safety and efficacy assessment

Dose Expansion

Part C of the study utilizes the RP2D to evaluate the anti-tumor activity of JIN-A02 in different cohorts based on EGFR mutation.

Ongoing until cohort completion

Regular visits for data collection and safety assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• JIN-A02

Trial Overview The trial is testing JIN-A02, a new oral drug for NSCLC patients with certain EGFR mutations who've seen their cancer progress post-treatment. It's in three parts: dose escalation to find the maximum tolerated dose, dose exploration for safety and optimal dosing levels, then expanding doses across different patient groups based on mutation type.

Participant Groups

Group I: Phase 1 dose-escalation, Phase 1 dose-exploratory, Phase 2 dose-expansion Experimental Treatment 1 Intervention

Single arm

Who Is Running the Clinical Trial?

J Ints Bio

Lead Sponsor

Trials

3

Recruited

150+

Findings from Research

The Jin formula, a traditional Chinese medicine, demonstrated significant anti-lung cancer effects in both in vitro and in vivo studies, effectively suppressing the proliferation, migration, and invasion of lung cancer cells.

The mechanism of action involves the up-regulation of miR-149-3p, which inhibits the expression of MAZ and down-regulates the Wnt/β-catenin signaling pathway, contributing to the anti-cancer effects of the Jin formula.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maimendong and Qianjinweijing Tang (Jin formula) suppresses lung cancer by regulation of miR-149-3p. Jiang, Z., Ma, Y., Tian, T., et al.[2021]

The Jin formula, when combined with cisplatin, significantly enhances the anti-tumor effects against non-small cell lung cancer (NSCLC) in a mouse model, while also reducing the side effects typically associated with cisplatin treatment.

The combination treatment works by inactivating the PI3K/AKT pathway and inducing apoptosis in tumor cells, leading to improved tumor suppression compared to cisplatin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study on Inhibitory Effect of MaiMenDong Decoction and WeiJing Decoction Combination with Cisplatin on NCI-A549 Xenograft in Nude Mice and Its Mechanism. Xiong, F., Jiang, M., Chen, M., et al.[2020]

Jin-Fu-An decoction significantly inhibits lung cancer cell growth, migration, and metastasis in a dose- and time-dependent manner, suggesting its potential as a therapeutic option for lung cancer.

The mechanism of action involves down-regulating p120ctn and its isoform 1A, while up-regulating the protein Kaiso, indicating a complex interaction that may help prevent cancer recurrence and metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Jinfu'an Decoction Inhibits Invasion and Metastasis in Human Lung Cancer Cells (H1650) via p120ctn-Mediated Induction and Kaiso. Sun, Z., Cao, Y., Hu, G., et al.[2023]

A network meta-analysis of 88 randomized controlled trials involving 6695 participants found that combining the NP regimen (Vinorelbine plus cisplatin) with specific Chinese herbal injections (CHIs) like Delisheng, Shenfu, and Shenmai significantly improved clinical effectiveness and performance status in patients with non-small cell lung cancer (NSCLC).

The combination of Shenfu injection with the NP regimen was particularly noted for its superior efficacy and safety compared to other Yiqi Fuzheng CHIs, although further high-quality trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A network meta-analysis: The best Yiqi Fuzheng Chinese herbal injections for use based on the NP regimen to treat NSCLC. Luo, H., Zheng, W., Yan, Q., et al.[2021]

Jinfu'an Decoction (JFAD) contains 32 herbal components that target 229 different pathways related to lung cancer metastasis, particularly influencing the PI3K/Akt signaling pathway.

Experimental studies demonstrated that JFAD effectively inhibits the growth and spread of non-small cell lung cancer (NSCLC) cells by inducing cell cycle arrest and downregulating key proteins, showing promise as a therapeutic option for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments. Peng, H., Huang, Z., Li, P., et al.[2023]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Maimendong and Qianjinweijing Tang (Jin formula) suppresses lung cancer by regulation of miR-149-3p. [2021]

2. Australia pubmed.ncbi.nlm.nih.gov

Study on Inhibitory Effect of MaiMenDong Decoction and WeiJing Decoction Combination with Cisplatin on NCI-A549 Xenograft in Nude Mice and Its Mechanism. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Jinfu'an Decoction Inhibits Invasion and Metastasis in Human Lung Cancer Cells (H1650) via p120ctn-Mediated Induction and Kaiso. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A network meta-analysis: The best Yiqi Fuzheng Chinese herbal injections for use based on the NP regimen to treat NSCLC. [2021]

5. Ireland pubmed.ncbi.nlm.nih.gov

Investigating the efficacy and mechanisms of Jinfu'an decoction in treating non-small cell lung cancer using network pharmacology and in vitro and in vivo experiments. [2023]