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RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2, Multicenter, Open-Label, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1324 in Participants With Advanced/Metastatic Gastrointestinal Tumors

NCT ID: NCT07263594Sponsor: DualityBio Inc.Last updated: 2026-05-22

Summary

This study, the first clinical trial, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of DB-1324.

Detailed description

This is a multicenter, open-label, multiple-dose, FIH Phase 1/2 study to explore the safety, tolerability, and efficacy of DB-1324 in participants with malignant GI tumors. The Phase 1, which includes Dose Escalation, Backfill, and Dose Expansion to identify the MTD and determine the RDEs and RP2D. Phase 2 will confirm the safety, tolerability, and explore efficacy in selected malignant GI tumors. For both Phase 1 and Phase 2, participants will receive study treatment until 1) disease progression, 2) loss of clinical benefit in the opinion of the investigator, 3) unacceptable toxicity, 4) withdrawal from study treatment by participant, 5) lost to follow up, or 6) another criterion for discontinuation is met, whichever occurs first.

Arms & interventions

  • DrugDB-1324

    Administered I.V.

Outcome measures

Primary

  • Dose Escalation and Backfill parts: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.

    Percentage of participants in dose escalation and backfill parts with DLTs

    Time frame: Up to safety follow-up visit, approximately 30 days post-treatment

  • Dose Escalation and Backfill parts: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.

    Percentage of participants with SAEs in dose escalation and backfill parts graded according to NCI CTCAE v5.0

    Time frame: Up to safety follow-up visit, approximately 30 days post-treatment

  • Dose Escalation and Backfill parts: Percentage of participants with Treatment Emergent Adverse Events (TEAEs) , Grade ≥ 3 TEAE, TEAE leading to dose reduction/interruption/discontinuation

    Percentage of participants who experienced any of the above TEAEs in dose escalation and backfill parts graded according to NCI CTCAE v5.0

    Time frame: Up to safety follow-up visit, approximately 30 days post-treatment

  • Dose Escalation and Backfill parts: Maximum Tolerated Dose(MTD) of DB-1324

    MTD will be determined by evaluating the incidence of DLTs during the DLT assessment period.

    Time frame: Up to safety follow-up visit, approximately 30 days post-treatment

Secondary

  • Dose Escalation and Backfill parts: Recommended Dose for Expansions(RDEs)

    Time frame: Up to the completion of Phase 1, assessed up to 12 months

  • Dose Escalation, Backfill and Expansion parts: Recommended Phase 2 Dose(RP2D)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Objective Response Rate (ORR)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Duration of Response (DoR)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Disease Control Rate (DCR)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Time to Response (TTR)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Progression Free Survival (PFS)

    Time frame: From the beginning of first patient in (FPI) to the end of study, approximately 36 months

  • Dose Escalation and Backfill parts: Pharmacokinetic-AUClast

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

  • Dose Escalation and Backfill parts: Pharmacokinetic-AUC0-τ

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

  • Dose Escalation and Backfill parts: Pharmacokinetic-Cmax

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

  • Dose Escalation and Backfill parts: Pharmacokinetic-Tmax

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

  • Dose Escalation and Backfill parts: Pharmacokinetic-Cthroug

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

  • Dose Escalation and Backfill parts: Anti-drug antibody (ADA) prevalence

    Time frame: Up to safety follow up visit, approx. 30 days post-treatment

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
Inclusion Criteria: 1. Pathologically documented advanced/unresectable, or metastatic GI tumor. 2. Have relapsed or progressed on or after standard systemic treatments, or are intolerant to standard treatment, or for which no standard treatment is available. 3. At least one measurable lesion as assessed by the investigator according to response evaluation criteria in RECIST v1.1. 4. Has a life expectancy of ≥ 3 months. 5. Has an ECOG PS of 0-1. 6. Has LVEF ≥ 50% by either ECHO or MUGA within 28 days before enrollment. 7. Has adequate organ functions within 7 days prior to Day 1 of Cycle 1. 8. Has an adequate treatment washout period before Day 1 of Cycle 1. 9. Participants are willing to provide archived tumor tissue or undergo a tumor biopsy for the measurement of CDH17 levels and other biomarkers. 10. Other protocol-defined Inclusion criteria apply. Exclusion Criteria: 1. Prior treatment with CDH17 targeted therapy. 2. Prior treatment with ADC with topoisomerase I inhibitor. 3. Has chronic enteritis or inflammatory bowel disease. Or has clinically significant bleeding of GI tract or adjacent organs within 1 month prior to the first dose of study treatment. Or has clinically significant obstruction and/or perforation and/or fistulae (including prior GI fistula operation) of GI tract or adjacent tissues within 6 months prior to the first dose of study treatment. 4. Uncontrolled or significant cardiovascular disease. 5. Has a medical history of cerebrovascular accident including transient ischemic attack within 6 months before enrollment. 6. Has a history of (non-infectious) ILD/pneumonitis that required steroids, or has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. 7. Have a lung-specific intercurrent clinically significant illness. 8. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals. 9. Has clinically active brain metastases. 10. Has unresolved toxicities from previous anticancer therapy. 11. Other protocol-defined Exclusion criteria apply.

Study locations (4)

USA05-0

Port Saint Lucie, Florida, 34952

Recruiting

USA02-0

Grand Rapids, Michigan, 49546

Recruiting

USA01-0

Huntersville, North Carolina, 28078

Recruiting

USA03-0

Cincinnati, Ohio, 45219

Recruiting