This study, the first clinical trial, aims to determine the safety, tolerability, pharmacokinetics, pharmacodynamics, maximum tolerated dose, and antitumor activity of DB-1324.
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
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
127
Administered I.V.
USA05-0
Port Saint Lucie, Florida, United States
RECRUITINGUSA02-0
Grand Rapids, Michigan, United States
RECRUITINGUSA01-0
Huntersville, North Carolina, United States
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
Dose Escalation and Backfill parts: Recommended Dose for Expansions(RDEs)
RDEs will be based on the data collected during dose escalation and backfill parts
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)
RP2D will be based on the data collected during dose escalation, backfill and expansion parts
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
USA03-0
Cincinnati, Ohio, United States
RECRUITINGAUS02-0
Randwick, New South Wales, Australia
RECRUITINGAUS03-0
South Brisbane, Queensland, Australia
RECRUITINGAUS01-0
Nedlands, Western Australia, Australia
RECRUITINGCHN01-0
Beijing, China
RECRUITINGCHN04-0
Beijing, China
RECRUITINGTime 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)
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
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)
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)
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)
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.
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)
TTR will be determined by investigator per RECIST v1.1, defined as the time from the first administration to first documented CR or PR.
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)
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.
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
Area under the concentration-time curve from time 0 to the last of DB-1324, total anti-CDH17 antibody, and unconjugated payload.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to safety follow up visit, approx. 30 days post-treatment
Dose Escalation and Backfill parts: Pharmacokinetic-Cthroug
Trough concentration
Time frame: 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
Time frame: Up to safety follow up visit, approx. 30 days post-treatment