A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors

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

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.

Study Overview

• Status: Recruiting
• Conditions: HER2-positive Advanced Solid Tumor
• Intervention / Treatment: Drug: Ritonavir; Drug: Itraconazole; Drug: Pertuzumab Injection; Biological: DB-1303/BNT323

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.

• Study Type: Interventional
• Enrollment (Estimated): 796
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Britney Winterberger; Phone Number: +1-513-403-8568; Email: britney.winterberger@tigermedgrp.com

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Active, not recruiting
      • Scientia Clinical Research Ltd
    • Sydney, New South Wales, Australia, 2109
      • Active, not recruiting
      • Macquarie Clinical Trials Unit
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Active, not recruiting
      • Integrated Clinical Oncology Network Pty Ltd (ICON)
  • Victoria
    • Melbourne, Victoria, Australia, 3168
      • Active, not recruiting
      • Monash Health
• China
  • Anhui
    • Bengbu, Anhui, China
      • Recruiting
      • The First Affiliated Hospital Of Bengbu Medical College
    • Hefei, Anhui, China
      • Recruiting
      • The Second Hospital of Anhui Medical University
    • Hefei, Anhui, China
      • Recruiting
      • Anhui Provincial Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China
      • Recruiting
      • Cancer Hospital Chinese Academy of Medical Science
  • Changchun
    • Hongcun, Changchun, China
      • Recruiting
      • The First Hospital of Jilin University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Recruiting
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing Municipality, China
      • Recruiting
      • Chongqing University Cancer Hospital
  • Fujian
    • Xiamen, Fujian, China
      • Recruiting
      • The First Affiliated Hospital of Xiamen University
  • Gansu
    • Lanzhou, Gansu, China
      • Recruiting
      • Gansu Provincial Maternity and Child-care Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Recruiting
      • The First Affiliated Hospital, Sun Yat-sen University
    • Guangzhou, Guangdong, China
      • Recruiting
      • Huizhou First Hospital
    • Guangzhou, Guangdong, China
      • Recruiting
      • Sun Yat-Sen Memorial Hospital of Zhongshan University
  • Guangxi
    • Nanning, Guangxi, China
      • Recruiting
      • Cancer Hospital of Guangxi Medical University
    • Yulin, Guangxi, China
      • Recruiting
      • The First People's Hospital of Yulin
  • Hebei
    • Baoding, Hebei, China
      • Recruiting
      • Affiliated Hospital of Hebei University
  • Hehan
    • Zhengzhou, Hehan, China
      • Recruiting
      • Henan Cancer Hospital
  • Henan
    • Anyang, Henan, China
      • Recruiting
      • Anyang Tumor Hospital
    • Zhengzhou, Henan, China
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Recruiting
      • Hunan People's Provincial Hospital
    • Changsha, Hunan, China
      • Recruiting
      • Hunan Cancer Hospital
    • Changsha, Hunan, China
      • Recruiting
      • Xiangya Hospital Central South University
  • Jiangsu
    • Changzhou, Jiangsu, China
      • Withdrawn
      • Changzhou Tumor Hospital
    • Wuxi, Jiangsu, China
      • Recruiting
      • Affiliated Hospital of Jiangnan University
    • Xuzhou, Jiangsu, China
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical College
    • Xuzhou, Jiangsu, China
      • Withdrawn
      • Xuzhou cancer hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Recruiting
      • Jiangxi Maternal and Child Health Hospital
    • Nanchang, Jiangxi, China
      • Recruiting
      • The Third Hospital of Nanchang
  • Jilin
    • Changchun, Jilin, China
      • Recruiting
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • Recruiting
      • The First Hospital of China Medical University
    • Shenyang, Liaoning, China
      • Recruiting
      • Liaoning Cancer Hospital & Institute
  • Shaanxi
    • Xi'an, Shaanxi, China
      • Recruiting
      • The First Affiliated Hospital of Xi'an Jiaotong University
  • Shandong
    • Jinan, Shandong, China
      • Recruiting
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Recruiting
      • Central Hospital Affiliated to Shandong First Medical University
    • Jinan, Shandong, China
      • Recruiting
      • Shandong Cancer Hospital & Institute
    • Jining, Shandong, China
      • Recruiting
      • Affiliated Hospital of Jining Medical University
    • Liaocheng, Shandong, China
      • Recruiting
      • Linyi Tumor Hospital
    • Zibo, Shandong, China
      • Recruiting
      • Zibo Central Hospital
  • Shangdong
    • Yantai, Shangdong, China
      • Withdrawn
      • Yantai Yuhuangding Hospital
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Fudan University
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Shanghai Tenth People's Hospital
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • The Obstetrics & Gynecology Hospital Affiliated to Fudan University
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China
      • Recruiting
      • Tianjin Medical University Cancer Institute & Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • Yunnan Provincial Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
    • Hangzhou, Zhejiang, China
      • Recruiting
      • 1st affliated hospital of Zhejiang University
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China
      • Recruiting
      • Women's Hospital School of Medicine Zhejiang University
    • Wenzhou, Zhejiang, China
      • Withdrawn
      • The First Affiliated Hospital of Wenzhou Medical University
• Puerto Rico
  • Mayagüez, Puerto Rico, 00682
    • Withdrawn
    • BRCR Global Puerto Rico LLC.
• South Korea
  • Bundang-gu
    • Gyeonggi-do, Bundang-gu, South Korea, 13620
      • Active, not recruiting
      • Seoul National University Bundang Hospital
  • Gangnam-gu
    • Seoul, Gangnam-gu, South Korea, 06351
      • Active, not recruiting
      • Samsung Medical Center
  • Ilsandong-gu
    • Gyeonggi-do, Ilsandong-gu, South Korea, 10408
      • Active, not recruiting
      • National Cancer Center
  • Seodaemun-gu
    • Seoul, Seodaemun-gu, South Korea, 03722
      • Active, not recruiting
      • Severance Hospital
  • Songpa-gu
    • Seoul, Songpa-gu, South Korea, 05505
      • Active, not recruiting
      • Asan Medical Center
• Taiwan
  • Beitou District
    • Taipei, Beitou District, Taiwan, 11217
      • Active, not recruiting
      • Taipei Veterans General Hospital
  • Changhua County
    • Changhua, Changhua County, Taiwan, 50006
      • Active, not recruiting
      • Changhua Christian Hospital
  • Xinyi District
    • Taipei, Xinyi District, Taiwan, 110301
      • Active, not recruiting
      • Taipei Medical University Hospital
  • Zhonghe District
    • Taipei, Zhonghe District, Taiwan, 235041
      • Active, not recruiting
      • Taipei Medical University-Shuang Ho Hospital
  • Zhongshan District
    • Taipei, Zhongshan District, Taiwan, 10449
      • Active, not recruiting
      • Mackay Memorial Hospital-Taipei
  • Zhongzheng District
    • Taipei, Zhongzheng District, Taiwan, 100225
      • Active, not recruiting
      • National Taiwan University Hospital
  • Zuoying District
    • Kaohsiung City, Zuoying District, Taiwan, 81362
      • Active, not recruiting
      • Kaohsiung Veterans General Hospital
• United States
  • California
    • Cerritos, California, United States, 90703
      • Active, not recruiting
      • Helios Clinical Research
    • Los Angeles, California, United States, 90027
      • Active, not recruiting
      • California Research Institute
    • San Diego, California, United States, 92123
      • Active, not recruiting
      • Sharp Memorial Hospital
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Active, not recruiting
      • Washington Cancer Institute at MedStar Washington Hospital Center
  • Florida
    • Coral Springs, Florida, United States, 33065
      • Active, not recruiting
      • Advanced Research LLC
    • Lakeland, Florida, United States, 33812
      • Active, not recruiting
      • The Oncology Institute of Hope and Innovation
    • Margate, Florida, United States, 33063
      • Active, not recruiting
      • D&H Cancer Research Center LLC
    • Miami, Florida, United States, 33133
      • Withdrawn
      • HCA Mercy Hospital
    • Plantation, Florida, United States, 33322
      • Active, not recruiting
      • BRCR Medical Center Inc.
    • Tamarac, Florida, United States, 33321
      • Active, not recruiting
      • BRCR Medical Center Inc.
  • Georgia
    • Newnan, Georgia, United States, 30265
      • Active, not recruiting
      • Southeastern Regional Medical Center, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96826
      • Active, not recruiting
      • Kapi'olani Medical Center for Women and Children
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Active, not recruiting
      • University of Chicago
  • Louisiana
    • Covington, Louisiana, United States, 70433
      • Withdrawn
      • Women'S Cancer Care
  • Maryland
    • Silver Spring, Maryland, United States, 20910
      • Withdrawn
      • Holy Cross Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Active, not recruiting
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02214
      • Active, not recruiting
      • Massachusetts General Hospital
  • Michigan
    • Dearborn, Michigan, United States, 48126
      • Withdrawn
      • Profound Research LLC/Michigan Hematology & Oncology Consultants
  • Missouri
    • St Louis, Missouri, United States, 63141
      • Active, not recruiting
      • David C. Pratt Cancer Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Withdrawn
      • Women's Cancer Center of Nevada
  • New York
    • Lake Success, New York, United States, 11042
      • Withdrawn
      • Northwell Health
    • New York, New York, United States, 10065
      • Active, not recruiting
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • Active, not recruiting
      • Laura & Isaac Perlmutter Cancer Center at NYC Langone Health
    • Shirley, New York, United States, 11967
      • Active, not recruiting
      • North Shore Hematology Oncology Associate P.C. DBA New York Cancer and Blood Specialists
  • North Carolina
    • Wilson, North Carolina, United States, 27893
      • Withdrawn
      • Regional Medical Oncology Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Active, not recruiting
      • Gabrail Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Active, not recruiting
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Active, not recruiting
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19107
      • Withdrawn
      • Rittenhouse Hematology Oncology
    • Pittsburgh, Pennsylvania, United States, 15224
      • Active, not recruiting
      • AHN West Penn Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Active, not recruiting
      • Tennessee Oncology
  • Texas
    • Houston, Texas, United States, 77074
      • Withdrawn
      • Clinical Trial Network
    • Laredo, Texas, United States, 78041
      • Active, not recruiting
      • Oncology and Hematology of South Texas, PA
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Active, not recruiting
      • Next Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Active, not recruiting
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

24

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DB-1303/BNT323 Dose Level 1; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 2; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 3; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 4; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 5; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 1; Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 2; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 3; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 4; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 5; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 6; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Level 7; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 6; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 7; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 8; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 9; Enrolled Subjects will be randomized to receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 on Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 11; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 12; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level 1 or dose level 2 in combination with Pertuzumab on Day 1 of each cycle Q3W	Drug: Pertuzumab Injection; Administered IV; Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 13; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 14; China Only:Subjects who were previously treated with trastuzumab and taxane will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 10; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W along with ritonavir or itraconazole to assess the DDI potential	Drug: Ritonavir; Administered oral; Drug: Itraconazole; Administered oral; Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 15; China Only: Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 16; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV
Experimental: DB-1303/BNT323 Dose Expansion 17; Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W	Biological: DB-1303/BNT323; Administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: 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 C1D1
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	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	Up to follow-up period, approximately 1 year post-treatment
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).	Up to Safety Follow-Up visit, approximately 35 days post-treatment
Phase 1: Maximum Tolerated Dose (MTD) of DB-1303	MTD on the data collected during Part 1	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	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).	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.	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)	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)	up to safety follow-up visit, approx. 35 days post-treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1	Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1.	Up to follow-up period, approximately 1 year post-treatment
Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1	The duration of time from date of first CR or PR to date of progressive disease or death due to any cause, whichever comes first using RECIST V1.1	Up to follow-up period, approximately 1 year post-treatment
Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1	The duration of time when receiving the first dose of study drug to the first date that is evaluated as either CR or PR using RECIST V1.1	Up to follow-up period, approximately 1 year post-treatment
Phase 2: Time on Therapy	The duration of time from participant receiving first dose of study drug to the last dose + 21 days	Up to 21 days after the participant's last dose
Phase 2: Percent change in target lesions as assessed by RECIST 1.1	The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1	Up to follow-up period, approximately 1 year post-treatment
Phase 1 & Phase 2: Pharmacokinetic-AUC	Area under the concentration-time curve from time 0 to infinity of DB-1303	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Cmax	Maximum observed plasma concentration (Cmax) of DB-1303	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Tmax	Time to Cmax of DB-1303	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-T1/2	Terminal elimination half-life	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacokinetic-Ctrough	Trough concentration of DB-1303	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 & Phase 2: Pharmacodynamics-ADA	Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline.	Up to safety follow up visit, approx. 35 days post-treatment
Phase 1 and 2 Cohort b only: Progression-Free Survival	Time from subject receiving the first dose to disease progression or death by any cause	Up to follow-up period, approximately 1 year post-treatment
Phase 1 and 2 Cohort b only: Overall Survival	Time from subject receiving the first dose to death by any cause	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	The percentage of subjects who had a best response of CR or PR	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	The percentage of subjects who had a best response of CR or PR, for Cohort 2b only	Up to follow-up period, approximately 1 year post-treatment
To evaluate the safety of DB-1303 with/without ritonavir or itraconazole	Percentage of Participants with Serious Adverse Events (SAEs), Treatment Emergent Adverse Events (TEAE), TEAEs >/= G3, or TEAEs leading to dose reduction, interruption or discontinuation, Adverse Events of Special Interest, (AESIs), abnormal vital signs, abnormal 12-lead ECGs, abnormal safety laboratory tests, abnormal ECOG PS, abnormal ECHO/MUGA (LVEF).	Up to follow-up period, approximately 1 year post-treatment

Collaborators and Investigators

• Sponsor: DualityBio Inc.
• Collaborators: BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2022
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: November 11, 2021
• First Submitted That Met QC Criteria: November 26, 2021
• First Posted (Actual): December 9, 2021

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 27, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: carcinoma; NSCLC; Non-Small Cell Lung Cancer; HER2; metastatic cancer; breast neoplasms; neoplasms; Cholangiocarcinoma; HER2-positive; stomach cancer; HER2-positive Breast Cancer; HER2-positive Gastric Cancer; HER2-positive Endometrial Cancer; HER2-positive Biliary Tract Cancer; HER2-positive Advanced Solid Tumor; HER2 low; HER2 high; HER2-positive GEJ; Uterine serous papillary carcinoma; USPC; recurrent cancer; gastrointestinal neoplasms; endometrial neoplasms; biliary tract neoplasms; Antineoplastic Agents, Biological; bile duct cancer; liver cancer; liver neoplasms; NSCLC HER2 mutation; HER2 Low Breast Cancer
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Disease Attributes; Respiratory Tract Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Uterine Diseases; Genital Diseases, Female; Lung Diseases; Biliary Tract Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Genital Neoplasms, Female; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Uterine Neoplasms; Bile Duct Diseases; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Neoplasms; Stomach Neoplasms; Biliary Tract Neoplasms; Recurrence; Carcinoma; Breast Neoplasms; Neoplasm Metastasis; Gastrointestinal Neoplasms; Liver Neoplasms; Carcinoma, Non-Small-Cell Lung; Cholangiocarcinoma; Endometrial Neoplasms; Bile Duct Neoplasms; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles; Triazoles; Piperazines; Ritonavir; Itraconazole; pertuzumab
• Other Study ID Numbers: DB-1303-O-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No