This is a dose-escalation and dose-expansion Phase 1/2a trial to evaluate the safety and tolerability of DB-1303/BNT323 in subjects with advanced solid tumors that express HER2.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Has a pathologically documented HER2-positive or HER2-expressing (except for cohort 2h where the requirement is HER2-null), advanced/unresectable, recurrent, or metastatic malignant solid tumor that is refractory to or intolerable with standard treatment, or for which no standard treatment is available.
* At least 1 measurable lesion (per RECIST 1.1)
* Provide signed informed consent
* ECOG performance status (PS) of 0-1.
* LVEF ≥ 50% by ECHO or MUGA
* Adequate organ functions
* Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing.
* Life expectancy of ≥ 3 months.
Additional Inclusion Criteria for Part 2 Expansion Group 9:
1\. Has pathologically documented advanced/unresectable, recurrent, or metastatic EC (including UCS and USPC) and has progressed on or after at least 1 line of systemic treatment including platinum-based therapy and exposure to ICI but no more than prior 3 lines of therapy for advanced/unresectable, or metastatic disease. Note: endocrine therapy will not qualify as a systemic therapy line.
Exclusion Criteria:
* History of symptomatic CHF (New York Heart Association \[NYHA\] classes II-IV) or serious cardiac arrhythmia requiring treatment.
* History of myocardial infarction or unstable angina within 6 months before Day 1.
* Average QTcF \> 450 ms in males and \> 470 ms in females
* History of clinically significant lung diseases
* Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
* HIV infection with AIDS defining illness or active viral hepatitis.
* Clinically active brain metastases
* Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline.
* A known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
* Part 2 (expansion) Only:Multiple primary malignancies within 3 years, except adequately resected non- melanoma skin cancer, curatively treated in-situ disease, other solid tumors curatively treated, or contralateral breast cancer.
Primary outcome measure(s)
Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0. — up to 21 days after C1D1 Percentage of participants in Part 1 with DLTs
Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0 — Up to Safety Follow-Up visit, approximately 35 days post-treatment Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).
Phase 1: 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 Part 1 graded according to NCI CTCAE v5.0
Phase 1: Maximum Tolerated Dose (MTD) of DB-1303 — Up to Safety Follow-Up visit, approximately 35 days post-treatment MTD on the data collected during Part 1
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303 — Up to Safety Follow-Up visit, approximately 35 days post-treatment RP2D of DB-1303 based on the data collected during Part 1
Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0 — Up to follow-up period, approximately 1 year post-treatment Phase 2: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) or Treatment Emergent Adverse Event of Special Interest include those \>/= G3 leading to dose reduction, interruption or discontinuation as assessed by CTCAE v5.0, abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).
Phase 2: Percentage 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 Part 2 graded according to NCI CTCAE v5.0
Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1. — Up to follow-up period, approximately 1 year post-treatment The percentage of subjects who had a best response of CR or PR, for Part 2 only which was maintained ≥4 weeks.
Phase 2 (Dose Expansion 10 only): To evaluate the effect of ritonavir on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors — up to safety follow-up visit, approx. 35 days post-treatment Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Ritonavir)
Phase 2 (Dose Expansion 10 only): To evaluate the effect of itraconazole on DB-1303 and P1003 PK in subjects with HER2-expressing, HER2-amplified, or HER2-mutated advanced solid malignant tumors. — up to safety follow-up visit, approx. 35 days post-treatment Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Itraconazole)
Trial sites (102)
Facility
City
Region
Status
Helios Clinical Research
Cerritos
California
Active Not Recruiting
California Research Institute
Los Angeles
California
Active Not Recruiting
Sharp Memorial Hospital
San Diego
California
Active Not Recruiting
Washington Cancer Institute at MedStar Washington Hospital Center
Washington D.C.
District of Columbia
Active Not Recruiting
Advanced Research LLC
Coral Springs
Florida
Active Not Recruiting
The Oncology Institute of Hope and Innovation
Lakeland
Florida
Active Not Recruiting
D&H Cancer Research Center LLC
Margate
Florida
Active Not Recruiting
HCA Mercy Hospital
Miami
Florida
Withdrawn
BRCR Medical Center Inc.
Plantation
Florida
Active Not Recruiting
BRCR Medical Center Inc.
Tamarac
Florida
Active Not Recruiting
Southeastern Regional Medical Center, LLC
Newnan
Georgia
Active Not Recruiting
Kapi'olani Medical Center for Women and Children
Honolulu
Hawaii
Active Not Recruiting
University of Chicago
Chicago
Illinois
Active Not Recruiting
Women's Cancer Care
Covington
Louisiana
Withdrawn
Holy Cross Hospital
Silver Spring
Maryland
Withdrawn
Massachusetts General Hospital
Boston
Massachusetts
Active Not Recruiting
Beth Israel Deaconess Medical Center
Boston
Massachusetts
Active Not Recruiting
Profound Research LLC/Michigan Hematology & Oncology Consultants
Dearborn
Michigan
Withdrawn
David C. Pratt Cancer Center
St Louis
Missouri
Active Not Recruiting
Women's Cancer Center of Nevada
Las Vegas
Nevada
Withdrawn
Northwell Health
Lake Success
New York
Withdrawn
Laura & Isaac Perlmutter Cancer Center at NYC Langone Health
New York
New York
Active Not Recruiting
Memorial Sloan Kettering Cancer Center
New York
New York
Active Not Recruiting
North Shore Hematology Oncology Associate P.C. DBA New York Cancer and Blood Specialists
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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