DB-1317 for selected advanced or metastatic solid tumors

A Phase 1a/1b, Multicenter, Open-Label, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1317 in Participants With Selected Advanced/Metastatic Solid Tumors

This study will try DB-1317, given every three weeks, in adults with advanced or metastatic solid tumors that have progressed after standard treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 233 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: DualityBio Inc. (Industry-sponsored)
• Locations: 6 sites (Los Angeles, California and 5 other locations)
• Trial ID: NCT07141706 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, multicenter Phase 1a/1b trial using an accelerated titration then BOIN dose-escalation design to find the maximum or maximum administered dose and assess safety. DB-1317 will be given every three weeks with a 21-day DLT observation period in Cycle 1 and staggered dosing early in each escalation level for safety. After dose escalation, up to three expansion cohorts (one randomized and two single-arm) will further evaluate safety, tolerability, and preliminary anti-tumor activity to identify a recommended Phase 2 dose. Participants must provide tumor tissue or undergo biopsy for ADAM9 expression and other biomarker analyses when feasible.

Who should consider this trial

Good fit: Adults with unresectable advanced or metastatic selected solid tumors that progressed after standard systemic therapy, ECOG 0–1, life expectancy ≥3 months, and willing to provide tumor tissue or a fresh biopsy are ideal candidates.

Not a fit: Patients who have received prior ADAM9-targeted therapy, have poor performance status (ECOG ≥2), very limited life expectancy, or who cannot provide tumor tissue are less likely to benefit.

Why it matters

Potential benefit: If successful, DB-1317 could shrink tumors or slow disease progression in patients with ADAM9-expressing advanced solid tumors.

How similar studies have performed: Targeting ADAM9 is a relatively novel approach with limited prior clinical data and mixed results from related ADAM-family or ADC strategies.

Eligibility criteria

Key Inclusion Criteria:

1. Male or female adults
2. Unresectable advanced or metastatic selected solid tumors that have relapsed or progressed on or after standard systemic treatments.
3. Only applicable to backfilling participants in Phase 1a and participants in Phase 1b: At least one measurable lesion as assessed by the investigator according to RECIST version 1.1 criteria. Participants with non-measurable disease are allowed for CRPC participants.
4. Has a life expectancy of ≥ 3 months.
5. Has an ECOG PS of 0-1.
6. Has LVEF ≥ 50% within 28 days before enrollment.
7. Is willing to provide pre-existing resected tumor samples or undergo fresh tumor biopsy for the measurement of ADAM9 expression level and other biomarkers if no contra-indication.
8. Male and female participants of reproductive/childbearing potential must agree to use adequate contraceptive methods

Key Exclusion Criteria:

1. Prior treatment with ADAM9 targeted therapy.
2. Prior treatment with antibody-drug conjugate with topoisomerase I inhibitor.
3. Has a medical history of symptomatic congestive heart failure or serious cardiac arrhythmia requiring treatment.
4. Has a medical history of myocardial infarction or unstable angina within 6 months before enrollment.
5. Has any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
6. Has an average of Fredericia's formula-QT corrected interval (QTcF) prolongation to \> 470 ms in males and females
7. Has a history of (non-infectious) ILD/pneumonitis
8. Has a lung-specific intercurrent clinically significant illness
9. Has an uncontrolled infection requiring intravenous injection of antibiotics, antivirals, or antifungals.
10. Known human immunodeficiency virus (HIV) infection;Chronic, active, or uncontrolled hepatitis B;
11. Known chronic, active, or uncontrolled hepatitis C
12. Has clinically significant corneal disease.
13. Has clinically active brain metastases
14. Has unresolved toxicities from previous anticancer therapy Concurrent malignancy \< 3 years.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Where this trial is running

Los Angeles, California and 5 other locations

• Usa04-0 — Los Angeles, California, United States (Recruiting)
• Site USA06-0 — Pittsburgh, Pennsylvania, United States (Recruiting)
• Usa02-0 — Houston, Texas, United States (Recruiting)
• Usa03-0 — San Antonio, Texas, United States (Recruiting)
• Usa01 — Fairfax, Virginia, United States (Recruiting)
• Aus01-0 — Randwick, New South Wales, Australia (Recruiting)

Study contacts

• Study coordinator: Junhua Gao

Conditions Advanced/Metastatic Solid Tumors; ADAM9; Solid tumor; DB-1317