A Study of DB-1324 in Advanced/Metastatic Gastrointestinal Tumors

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

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

Study Overview

• Status: Recruiting
• Conditions: Gastrointestinal Cancer
• Intervention / Treatment: Drug: 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.

• Study Type: Interventional
• Enrollment (Estimated): 127
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Zhaochuan Wang; Phone Number: 4123279868; Email: zhaochuan.wang@dualitybiologics.com
• Study Contact Backup: Name: Yuanyuan Sun; Email: yuanyuan.sun@dualitybiologics.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • AUS02-0
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Recruiting
      • AUS03-0
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • AUS01-0
• China
  • Beijing, China, 100142
    • Recruiting
    • CHN01-0
  • Beijing, China, 102206
    • Recruiting
    • CHN04-0
• United States
  • Florida
    • Port Saint Lucie, Florida, United States, 34952
      • Recruiting
      • USA05-0
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Recruiting
      • USA02-0
  • North Carolina
    • Huntersville, North Carolina, United States, 28078
      • Recruiting
      • USA01-0
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • USA03-0

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DB-1324 Phase 1 Dose escalation; Enrolled Subjects will receive a single-dose of DB-1324 at different Dose Level or different dose regimen	Drug: DB-1324; Administered I.V.
Experimental: DB-1324 Phase 1 Backfill; Participants with GI cancers who have received no more than 3 prior lines of systemic therapy may be backfilled at the selected dose regimens to further explore the safety, efficacy, PK, and pharmacodynamics of DB-1324.	Drug: DB-1324; Administered I.V.
Experimental: DB-1324 Phase 1 Dose Expansion; Two or more appropriate dose regimens of DB-1324, determined from the emerging dose escalation (and backfill) data, will be explored for preliminary efficacy and safety of DB-1324.	Drug: DB-1324; Administered I.V.
Experimental: DB-1324 Phase 2; Phase 2 will consist of one or more cohorts intended to confirm early signals of efficacy identified in Phase 1.	Drug: DB-1324; Administered I.V.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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.	Up to safety follow-up visit, approximately 30 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Escalation and Backfill parts: Recommended Dose for Expansions(RDEs)	RDEs will be based on the data collected during dose escalation and backfill parts	Up to the completion of Phase 1, assessed up to 12 months
Dose Escalation, Backfill and Expansion parts: Recommended Phase 2 Dose(RP2D)	RP2D will be based on the data collected during dose escalation, backfill and expansion parts	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)	ORR will be determined by investigator per RECIST v1.1, defined as the percentage of participants who had a best response rating of CR and PR	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)	DoR will be determined by investigator per RECIST v1.1, defined as the time from earliest date of documented CR or PR to the date of documented disease progression or death (by any cause, in the absence of progression)	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)	DCR will be determined by investigator per RECIST v1.1, defined as the proportion of participants with best overall response of CR, PR, or SD with confirmation over a period of at least 6 weeks.	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)	TTR will be determined by investigator per RECIST v1.1, defined as the time from the first administration to first documented CR or PR.	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)	PFS will be determined by investigator per RECIST v1.1, defined as the time from the first administration to documented disease progression or death (by any cause, in the absence of progression), whichever occurs first.	From the beginning of first patient in (FPI) to the end of study, approximately 36 months
Dose Escalation and Backfill parts: Pharmacokinetic-AUClast	Area under the concentration-time curve from time 0 to the last of DB-1324, total anti-CDH17 antibody, and unconjugated payload.	Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Pharmacokinetic-AUC0-τ	Area under the concentration-time curve from time 0 to time tau of DB-1324, total anti-CDH17 antibody, and unconjugated payload.	Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Pharmacokinetic-Cmax	Maximum observed plasma concentration (Cmax) of DB-1324, total anti-CDH17 antibody, and unconjugated payload.	Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Pharmacokinetic-Tmax	Time to Cmax of DB-1324, total anti-CDH17 antibody, and unconjugated payload.	Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Pharmacokinetic-Cthroug	Trough concentration	Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Anti-drug antibody (ADA) prevalence	Percentage of participants who are ADA positive at any point	Up to safety follow up visit, approx. 30 days post-treatment

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Collaborators: GlaxoSmithKline
• Investigators: Study Director: Lily Hu, DualityBio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): December 4, 2025

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Gastrointestinal Tumors, DB-1324
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms
• Other Study ID Numbers: DB-1324-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No