A Phase Ⅰ/Ⅱa Clinical Study of GEN-725 in Combination With Dositinib

ConditionNon-Small Cell Lung Cancer

Trial statusRecruiting

Trial phasePhase 1, Phase 2

Trial typeInterventional

Biological sexAll

Age18-75

SponsorHenan Genuine Biotech Co., Ltd.

About this trial

This is an open-label phase I/phase II clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of GEN-725 in combination with Dositinib in participants with locally advanced or metastatic EGFR-mutant non-small cell lung cancer.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

18-75 years old (including 18 and 75 years old), male or female.

Patients with histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) who are not amenable to curative surgery or radiotherapy. (For subjects naive to EGFR-TKI therapy, paraffin-embedded tissue blocks, unstained slides, or fresh tumor tissue samples must be available for EGFR testing.)

Patients with a positive EGFR mutation. (For patients with prior third-generation EGFR-TKI therapy, post-progression EGFR mutation test results are recommended.)

a) Phase Ⅰ Dose Escalation Stage: EGFR-mutant NSCLC patients who have received at least one prior line of therapy (chemotherapy or targeted therapy are allowed). Patients who have received prior neoadjuvant, adjuvant, and/or radical concurrent/sequential chemoradiotherapy (including chemotherapy, immunotherapy, targeted therapy, etc.) must have documented disease recurrence or progression within <6 months of completing the last regimen. b) Phase Ⅱa Dose Expansion Stage: Cohort 1: NSCLC patients with disease progression on a prior third-generation EGFR-TKI. Cohort 2: EGFR mutant NSCLC patients who are EGFR-TKI-naive.

Disqualifiers

Undergone major surgery within 4 weeks prior to the first administration;

Antitumor therapy including chemotherapy, immunotherapy, targeted therapy, etc., within 4 weeks prior to the first administration; for oral small-molecule targeted drugs, within 2 weeks or within 5 half-lives prior to the first administration (whichever is shorter);

Radiation therapy involving >30% of the bone marrow or large-field radiation therapy within 4 weeks prior to the first administration;

Strong inhibitors or inducers of CYP3A4 within 7 days prior to the first administration;

Trial design

Design model

Sequential

Treatments tested in this trial

GEN-725 tablets + Dositinib mesylate tablets
Drug
Dose-escalation part (Phase Ⅰ): Subjects will receive once-daily oral administration of GEN-725 tablets in combination with Dositinib mesylate tablets on an empty stomach. GEN-725 will be administered at a dose of 6 mg or 9 mg, and Dositinib will be administered at a dose of 80 mg or 160 mg. Both drugs should be taken concurrently. The treatment will continue until the first occurrence of any of the following: disease progression, unacceptable toxicity, withdrawal of consent, or investigator's determination of no further clinical benefit. Dose-expansion part (Phase Ⅱa): Subjects will receive once-daily oral administration of GEN-725 tablets in combination with Dositinib mesylate tablets or Dositinib mesylate tablets alone on an empty stomach. The dose will be selected based on the outcome of dose-escalation phase. The treatment will continue until the first occurrence of any criterion that was specified in the dose-escalation part.

Treatment groups

110 Participants

are divided into 1 treatment group

Group A: ExperimentalExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Number of Subjects with Dose Limiting Toxicity (DLT) in Phase Ⅰ

Time frame

From Day 1 to Day 21 of Cycle1 (each cycle is 21 days).

Incidence and severity of adverse events (AEs) in Phase Ⅰ and Phase Ⅱa

AEs are assessed based on NCI CTCAE v5.0.

Time frame

From the time of informed consent until 28 days after the last administration of the study drugs.

Objective Response Rate (ORR) in Phase Ⅱa

Time frame