RecruitingInterventionalPhase 1/Phase 2

A Phase 1/2a, Multicenter, Open-Label, First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303/BNT323 in Patients With Advanced/Metastatic Solid Tumors

NCT ID: NCT05150691Sponsor: DualityBio Inc.Last updated: 2026-01-28

Summary

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.

Detailed description

This is a multicenter, non-randomized (Except for Dose Expansion 1 and Dose Expansion 9 cohorts), open-label, multiple-dose, FIH study. The study consists of two parts: Part 1 adopts an accelerated titration at first dose level followed with classic "3+3" design to identify the MTD/RP2D; Part 2 is a dose expansion phase to confirm the safety, tolerability and explore efficacy in selected malignant solid tumors at the MTD/the RP2D. This study will enroll subjects with advanced/unresectable, recurrent, or metastatic HER2-expressing malignant solid tumors.

Arms & interventions

BiologicalDB-1303/BNT323
Administered IV
DrugPertuzumab Injection
Administered IV
DrugRitonavir
Administered oral
DrugItraconazole
Administered oral

Outcome measures

Primary

Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
Percentage of participants in Part 1 with DLTs
Time frame: up to 21 days after C1D1
Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
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).
Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
Percentage of Participants with SAEs in Part 1 graded according to NCI CTCAE v5.0
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 1: Maximum Tolerated Dose (MTD) of DB-1303
MTD on the data collected during Part 1
Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303
RP2D of DB-1303 based on the data collected during Part 1
Time frame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
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).
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
Percentage of participants with SAEs in Part 2 graded according to NCI CTCAE v5.0
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
The percentage of subjects who had a best response of CR or PR, for Part 2 only which was maintained ≥4 weeks.
Time frame: Up to follow-up period, approximately 1 year post-treatment
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
Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Ritonavir)
Time frame: up to safety follow-up visit, approx. 35 days post-treatment
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.
Maximum observed plasms concentration (Cmax) and Area under the concentration-time curve from 0 to infinity of DB-1303 and P1003 (+/- Itraconazole)
Time frame: up to safety follow-up visit, approx. 35 days post-treatment

Secondary

Phase 1 & Phase 2: Pharmacokinetic-AUC
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Cmax
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Tmax
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-T1/2
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Ctrough
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacodynamics-ADA
Time frame: Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 2: Time on Therapy
Time frame: Up to 21 days after the participant's last dose
Phase 2: Percent change in target lesions as assessed by RECIST 1.1
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 1 and 2 Cohort b only: Progression-Free Survival
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 1 and 2 Cohort b only: Overall Survival
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1
Time frame: Up to follow-up period, approximately 1 year post-treatment
Phase 2 Cohort b Only: Percentage of ORR as assessed by IRC and as assessed by investigator based on RECIST 1.1 for HER2-expressing subjects and in subjects with prior ICI treatment
Time frame: Up to follow-up period, approximately 1 year post-treatment
To evaluate the safety of DB-1303 with/without ritonavir or itraconazole
Time frame: Up to follow-up period, approximately 1 year post-treatment

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy 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.

Study locations (35)

Helios Clinical Research

Cerritos, California, 90703

Active Not Recruiting

California Research Institute

Los Angeles, California, 90027

Active Not Recruiting

Sharp Memorial Hospital

San Diego, California, 92123

Active Not Recruiting

Washington Cancer Institute at MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010

Active Not Recruiting

Advanced Research LLC

Coral Springs, Florida, 33065

Active Not Recruiting

The Oncology Institute of Hope and Innovation

Lakeland, Florida, 33812

Active Not Recruiting

D&H Cancer Research Center LLC

Margate, Florida, 33063

Active Not Recruiting

HCA Mercy Hospital

Miami, Florida, 33133

Withdrawn

BRCR Medical Center Inc.

Plantation, Florida, 33322

Active Not Recruiting

BRCR Medical Center Inc.

Tamarac, Florida, 33321

Active Not Recruiting

Southeastern Regional Medical Center, LLC

Newnan, Georgia, 30265

Active Not Recruiting

Kapi'olani Medical Center for Women and Children

Honolulu, Hawaii, 96826

Active Not Recruiting

University of Chicago

Chicago, Illinois, 60637

Active Not Recruiting

Women's Cancer Care

Covington, Louisiana, 70433

Withdrawn

Holy Cross Hospital

Silver Spring, Maryland, 20910

Withdrawn

Massachusetts General Hospital

Boston, Massachusetts, 02214

Active Not Recruiting

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215

Active Not Recruiting

Profound Research LLC/Michigan Hematology & Oncology Consultants

Dearborn, Michigan, 48126

Withdrawn

David C. Pratt Cancer Center

St Louis, Missouri, 63141

Active Not Recruiting

Women's Cancer Center of Nevada

Las Vegas, Nevada, 89106

Withdrawn

Northwell Health

Lake Success, New York, 11042

Withdrawn

Laura & Isaac Perlmutter Cancer Center at NYC Langone Health

New York, New York, 10016

Active Not Recruiting

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

Active Not Recruiting

North Shore Hematology Oncology Associate P.C. DBA New York Cancer and Blood Specialists

Shirley, New York, 11967

Active Not Recruiting

Regional Medical Oncology Center

Wilson, North Carolina, 27893

Withdrawn

Gabrail Cancer Center

Canton, Ohio, 44718

Active Not Recruiting

University of Oklahoma

Oklahoma City, Oklahoma, 73104

Active Not Recruiting

Rittenhouse Hematology Oncology

Philadelphia, Pennsylvania, 19107

Withdrawn

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107

Active Not Recruiting

AHN West Penn Hospital

Pittsburgh, Pennsylvania, 15224

Active Not Recruiting

Tennessee Oncology

Nashville, Tennessee, 37203

Active Not Recruiting

Clinical Trial Network

Houston, Texas, 77074

Withdrawn

Oncology and Hematology of South Texas, PA

Laredo, Texas, 78041

Active Not Recruiting

NEXT Virginia

Fairfax, Virginia, 22031

Active Not Recruiting

Swedish Cancer Institute

Seattle, Washington, 98104

Active Not Recruiting