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

DualityBio

Status and phase: Not yet enrolling; Phase 2; Phase 1

Conditions: Gastrointestinal Cancer

Treatments: Drug: DB-1324

Study type: Interventional

Funder types: Industry

Identifiers

NCT07263594

DB-1324-101

Details and patient eligibility

About

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

Full 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.

Enrollment: 127 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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127 participants in 4 patient groups

DB-1324 Phase 1 Dose escalation

Experimental group

Description:

Enrolled Subjects will receive a single-dose of DB-1324 at different Dose Level or different dose regimen

Treatment:

Drug: DB-1324

DB-1324 Phase 1 Backfill

Experimental group

Description:

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.

Treatment:

Drug: DB-1324

DB-1324 Phase 1 Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: DB-1324

DB-1324 Phase 2

Experimental group

Description:

Phase 2 will consist of one or more cohorts intended to confirm early signals of efficacy identified in Phase 1.

Treatment:

Drug: DB-1324