NCT07362940
Recruiting
Phase 1
A Phase Ⅰ/Ⅱa Clinical Study Evaluating the Efficacy and Safety of GEN-725 in Combination With Dositinib in Patients With Locally Advanced or Metastatic EGFR-Mutant Non-small Cell Lung Cancer
Henan Genuine Biotech Co., Ltd.5 sites in 1 country110 target enrollmentStarted: November 27, 2025Last updated:
InterventionsGEN-725 tablets + Dositinib mesylate tablets
Overview
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Henan Genuine Biotech Co., Ltd.
- Enrollment
- 110
- Locations
- 5
- Primary Endpoint
- Number of Subjects with Dose Limiting Toxicity (DLT) in Phase Ⅰ
Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
- •Patients with at least one measurable or evaluable lesion per RECIST 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a life expectancy of at least 12 weeks.
- •Adequate organ function must meet the following criteria (with no transfusion of blood, blood products, no administration of hematopoietic growth factors, or no infusion of albumin/blood products within 14 days before laboratory testing):
- •Absolute neutrophil (NE) count ≥ 1.5 × 10\^9/L.
- •Platelet (PLT) count ≥ 100 × 10\^9/L.
- •Hemoglobin (HGB) ≥ 100 g/L.
Exclusion Criteria
- •Patients have previously received any of the following treatments:
- •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;
- •Traditional Chinese medicine (TCM) or TCM preparations that have antitumor indications, or that are intended for tumor adjuvant therapy within 14 days prior to the first administration;
- •Presence of unresolved toxicities from previous anticancer therapy, with Common Terminology Criteria for Adverse Events (CTCAE) v5.0 grade \>1 (except alopecia) at the start of study treatment. The pre-existing neuropathy from previous platinum-therapy is allowed up to grade 2;
- •Patients with meaningful bypass mutations of corresponding marketed drugs, including but not limited to: MET exon 14 skipping mutation, MET amplification, ALK fusion, HER-2 mutation, ROS-1 fusion, RET fusion, BRAF V600E mutation, KRAS G12C, NTRK fusion, etc. (Applicable only to the dose expansion period, and will be adjusted according to the gene detection results from the dose escalation period);
- •Patients with disease progression (PD) or stable disease (SD) with a duration of ≤3 months following treatment with a third-generation EGFR-TKI;
- •Patients with any uncontrolled systemic disease, as determined by the investigator, such as uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg after optimal medical therapy), uncontrolled diabetes, coronary artery stenosis, aortic dissection, aortic aneurysm, active bleeding diathesis, etc.;
Arms & Interventions
Experimental
Experimental
Dose-escalation part and dose-expansion part
Intervention: GEN-725 tablets + Dositinib mesylate tablets (Drug)
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
Time Frame: From the time of informed consent until 28 days after the last administration of the study drugs.
AEs are assessed based on NCI CTCAE v5.0.
Objective Response Rate (ORR) in Phase Ⅱa
Time Frame: Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.
Intracranial Objective Response Rate (iORR) in Phase Ⅱa
Time Frame: Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.
Secondary Outcomes
- Objective Response Rate (ORR) in Phase Ⅰ(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Disease Control Rate (DCR) in Phase Ⅰ and Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Progression-Free Survival (PFS) in Phase Ⅰ and Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Duration of Response (DOR) in Phase Ⅰ and Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Overall Survival (OS) in Phase Ⅰ and Phase Ⅱa(Every 12 weeks after the last dose, up to 5 years, up to 5 years.)
- Intracranial Progression-Free Survival (iPFS) in Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Intracranial Disease Control Rate (iDCR) in Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Intracranial Duration of Response (iDOR) in Phase Ⅱa(Every 6 weeks during the first year and every 12 weeks thereafter, up to 5 years.)
- Maximum Plasma Concentration (Cmax) of GEN-725 and Dositinib(Up to 24 hours post-dose.)
- Elimination Half-Life (t1/2) of GEN-725 and Dositinib(Up to 24 hours post-dose.)
- Area Under the Plasma Concentration Curve (AUC) of GEN-725 and Dositinib(Up to 24 hours post-dose.)
Investigators
Study Sites (5)
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