This is a multicenter, open-label, multiple-dose, FIH Phase 1a/1b study. Phase 1a adopts an accelerated titration design and a BOIN design to identify the MTD or MAD of DB-1317; Phase 1b includes one randomized dose expansion cohort and two single-arm dose expansion cohorts to further evaluate the safety, tolerability and preliminary efficacy of DB-1317 in selected solid tumors and to identify optimal RP2D.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
Primary outcome measure(s)
Phase 1a: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. Percentage of participants in Part 1 with DLTs — up to 21 days after Cycle 1 Day 1 Percentage of participants in Phase 1a with DLTs
Phase 1a: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0. — Up to follow-up period, approximately 1 year post-treatment Percentage of participants with TEAEs in Phase 1a graded according to NCI CTCAE v5.0
Phase 1a: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. — Up to follow-up period, approximately 1 year post-treatment Percentage of Participants with SAEs in Phase 1a graded according to NCI CTCAE v5.0
Maximum Tolerated Dose (MTD) of DB-1317 — Up to the completion of Phase 1a (assessed up to 12 months) MTD on the data collected during Phase 1a
Recommended Phase 1b Dose (RP2D) of DB-1317 — Up to the completion of Phase 1a (assessed up to 12 months) RP2D of DB-1317 based on the data collected during Phase 1a
Phase 1b: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0. — Up to follow-up period, approximately 1 year post-treatment Percentage of participants with TEAEs in Phase 1b graded according to NCI CTCAE v5.0
Phase 1b: Percentage of participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0. — Up to follow-up period, approximately 1 year post-treatment Percentage of participants with SAEs in Phase 1b graded according to NCI CTCAE v5.0
Phase 1b: Objective Response Rate (ORR) as determined by investigator — Up to follow-up period, approximately 1 year post-treatment Phase 1b: Objective Response Rate (ORR) as determined by investigator per RECIST 1.1 in non-CRPC. The percentage of participants who had a best response rating of CR and PR, for Part 2 only which was maintained ≥4 weeks
Phase 1b: duration of response (DoR) — Up to follow-up period, approximately 1 year post-treatment DoR will be determined from tumor assessments by investigator per response evaluation criteria in solid tumors version 1.1 (RECIST v1.1)
Phase 1b: disease-control rate (DCR) — Up to follow-up period, approximately 1 year post-treatment DCR will be determined from tumor assessments by investigator per response
Phase 1b: Time to Response (TTR) — Up to follow-up period, approximately 1 year post-treatment TTR will be determined from tumor assessments by investigator per response
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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