Clinical trial NCT05150691: A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: HER2-positive Advanced Solid Tumor
Keywords: HER2
HER2-positive
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
metastatic cancer
HER2-positive GEJ
Uterine serous papillary carcinoma
USPC
recurrent cancer
carcinoma
neoplasms
breast neoplasms
gastrointestinal neoplasms
endometrial neoplasms
biliary tract neoplasms
Antineoplastic Agents, Biological
stomach cancer
bile duct cancer
Cholangiocarcinoma
liver cancer
liver neoplasms
NSCLC
Non-Small Cell Lung Cancer
NSCLC HER2 mutation
HER2 Low Breast Cancer
Lead sponsor: DualityBio Inc.
Sponsor class: INDUSTRY
Collaborators: name: BioNTech SE
First posted: 2021-12-09
Enrollment: 796
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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 outcomes:
measure: Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
timeFrame: up to 21 days after C1D1
measure: Phase 1: Percentage of participants with AEs in Part 1 graded according to NCI CTCAE v5.0
timeFrame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
measure: Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1: Maximum Tolerated Dose (MTD) of DB-1303
timeFrame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
measure: Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303
timeFrame: Up to Safety Follow-Up visit, approximately 35 days post-treatment
measure: Percentage of participants with AEs in Part 2 graded according to NCI CTCAE v5.0
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 2: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 2: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: 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
timeFrame: up to safety follow-up visit, approx. 35 days post-treatment
measure: 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.
timeFrame: up to safety follow-up visit, approx. 35 days post-treatment
Secondary outcomes:
measure: Phase 1 & Phase 2: Pharmacokinetic-AUC
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & Phase 2: Pharmacokinetic-Cmax
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & Phase 2: Pharmacokinetic-Tmax
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & Phase 2: Pharmacokinetic-T1/2
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & Phase 2: Pharmacokinetic-Ctrough
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & Phase 2: Pharmacodynamics-ADA
timeFrame: Up to safety follow up visit, approx. 35 days post-treatment
measure: Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 2: Time on Therapy
timeFrame: Up to 21 days after the participant's last dose
measure: Phase 2: Percent change in target lesions as assessed by RECIST 1.1
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1 and 2 Cohort b only: Progression-Free Survival
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase 1 and 2 Cohort b only: Overall Survival
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on RECIST 1.1
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: 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
timeFrame: Up to follow-up period, approximately 1 year post-treatment
measure: To evaluate the safety of DB-1303 with/without ritonavir or itraconazole
timeFrame: Up to follow-up period, approximately 1 year post-treatment
Other outcomes:
Locations:
city: Cerritos
country: United States
facility: TOI Clinical Research
state: California
city: Los Angeles
country: United States
facility: California Research Institute
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Washington
country: United States
facility: Washington Cancer Institute at MedStar Washington Hospital Center
state: District of Columbia
city: Coral Springs
country: United States
facility: Advanced Research LLC
state: Florida
city: Lakeland
country: United States
facility: The Oncology Institute of Hope and Innovation
state: Florida
city: Margate
country: United States
facility: D&H Cancer Research Center LLC
state: Florida
city: Miami
country: United States
facility: HCA Mercy Hospital
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Tamarac
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Newnan
country: United States
facility: Southeastern Regional Medical Center, LLC
state: Georgia
city: Honolulu
country: United States
facility: Kapi'olani Medical Center for Women and Children
state: Hawaii
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Covington
country: United States
facility: Women's Cancer Care
state: Louisiana
city: Silver Spring
country: United States
facility: Holy Cross Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Dearborn
country: United States
facility: Profound Research LLC/Michigan Hematology & Oncology Consultants
state: Michigan
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center
state: Missouri
city: Las Vegas
country: United States
facility: Women's Cancer Center of Nevada
state: Nevada
city: Lake Success
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYC Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Shirley
country: United States
facility: North Shore Hematology Oncology Associate P.C. DBA New York Cancer and Blood Specialists
state: New York
city: Wilson
country: United States
facility: Regional Medical Oncology Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Rittenhouse Hematology Oncology
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: AHN West Penn Hospital
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: Clinical Trial Network
state: Texas
city: Laredo
country: United States
facility: Oncology and Hematology of South Texas, PA
state: Texas
city: Fairfax
country: United States
facility: NEXT Virginia
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Randwick
country: Australia
facility: Scientia Clinical Research LTD
state: New South Wales
city: Sydney
country: Australia
facility: Macquarie Clinical Trials Unit
state: New South Wales
city: South Brisbane
country: Australia
facility: Integrated Clinical Oncology Network Pty Ltd (Icon)
state: Queensland
city: Melbourne
country: Australia
facility: Monash Health
state: Victoria
city: Bengbu
country: China
facility: The first affiliated hospital of Bengbu medical college
state: Anhui
city: Hefei
country: China
facility: Anhui provincial hospital
state: Anhui
city: Hefei
country: China
facility: The Second Hospital of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Science
state: Beijing
city: Jilian
country: China
facility: The First Hospital of Jilin University
state: Changchun
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Chongqing
country: China
facility: The First affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Xiamen
country: China
facility: The First affiliated hospital of Xiamen University
state: Fujian
city: Lanzhou
country: China
facility: Gansu Provincial Maternity and Child-care Hospital
state: Gansu
city: Guangzhou
country: China
facility: Huizhou First Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Sun Yat-Sen Memorial Hospital of Zhongshan University
state: Guangdong
city: Guangzhou
country: China
facility: The First affiliated hospital, Sun Yat-sen University
state: Guangdong
city: Nanning
country: China
facility: Cancer Hospital of Guangxi Medical University
state: Guangxi
city: Yulin
country: China
facility: The First people's hospital of Yulin
state: Guangxi
city: Baoding
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Zhengzhou
country: China
facility: Henan cancer Hospital
state: Hehan
city: Anyang
country: China
facility: Anyang Tumor Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union hospital Tongji Medical college Huazhong university of science and technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Changsha
country: China
facility: Hunan People's Provincial Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changzhou
country: China
facility: Changzhou Tumor Hospital
state: Jiangsu
city: Wuxi
country: China
facility: Affiliated Hospital of Jiangnan University
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical College
state: Jiangsu
city: Xuzhou
country: China
facility: Xuzhou Cancer Hospital
state: Jiangsu
city: Nanchang
country: China
facility: Jiangxi maternal and child health hospital
state: Jiangxi
city: Nanchang
country: China
facility: The Third Hospital of Nanchang
state: Jiangxi
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Shenyang
country: China
facility: Liaoning cancer hospital & Institute
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Xi'an
country: China
facility: The First Affiliated Hospital Of Xi'an Jiaotong University
state: Shaanxi
city: Jinan
country: China
facility: Central hospital affiliated to Shandong first medical university
state: Shandong
city: Jinan
country: China
facility: Jinan Central Hospital
state: Shandong
city: Jinan
country: China
facility: Shandong Cancer hospital & institute
state: Shandong
city: Jining
country: China
facility: Affiliated hospital of Jining medical university
state: Shandong
city: Liaocheng
country: China
facility: Linyi Tumor Hospital
state: Shandong
city: Zibo
country: China
facility: Zibo Central hospital
state: Shandong
city: Yantai
country: China
facility: Yantai Yuhuangding Hospital
state: Shangdong
city: Shanghai
country: China
facility: Fudan University
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Tenth people's Hospital
state: Shanghai
city: Shanghai
country: China
facility: The Obstetrics & Gynecology Hospital Affiliated to Fudan University
state: Shanghai
city: Tianjin
country: China
facility: Tianjin Medical university cancer institute & hospital
state: Tianjin
city: Kunming
country: China
facility: Yunnan Provincial Cancer Hospital
state: Yunnan
city: Hangzhou
country: China
facility: 1st affliated hospital of Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: The second affiliated hospital of Zhejiang University School of Medicine
state: Zhejiang
city: Hangzhou
country: China
facility: Women's hospital school of medicine Zhejiang University
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Mayaguez
country: Puerto Rico
facility: BRCR Global Puerto Rico LLC.
Study officials:
References: