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
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
Study locations (4)
USA05-0
Port Saint Lucie, Florida, 34952
USA02-0
Grand Rapids, Michigan, 49546
USA01-0
Huntersville, North Carolina, 28078
USA03-0
Cincinnati, Ohio, 45219