A Phase 1/2a Study of DB-1303/BNT323 in Advanced/Metastatic Solid Tumors
- Conditions
- HER2-positive Advanced Solid Tumor
- Interventions
- Registration Number
- NCT05150691
- Lead Sponsor
- DualityBio Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 796
- 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:
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description DB-1303/BNT323 Dose Level 1 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 1 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 2 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 2 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 3 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 3 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 4 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 4 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 5 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 5 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 1 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 2 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 3 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 4 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 5 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 6 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 6 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Level 7 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 at Dose Level 7 on Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 6 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 7 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 8 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 9 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 10 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 10 Ritonavir 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 DB-1303/BNT323 Dose Expansion 10 Itraconazole 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 DB-1303/BNT323 Dose Expansion 11 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 12 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 12 Pertuzumab Injection 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 DB-1303/BNT323 Dose Expansion 13 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 14 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 15 DB-1303/BNT323 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 DB-1303/BNT323 Dose Expansion 16 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W DB-1303/BNT323 Dose Expansion 17 DB-1303/BNT323 Enrolled Subjects will receive a single-dose of DB-1303/BNT323 on a selected dose level (RP2D) Day 1 of each cycle Q3W
- Primary Outcome Measures
Name Time Method 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: 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
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 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 (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)
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.
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).
- Secondary Outcome Measures
Name Time Method Phase 1 & Phase 2: Pharmacokinetic-Tmax Up to safety follow up visit, approx. 35 days post-treatment Time to Cmax of DB-1303
Phase 1 & Phase 2: Pharmacokinetic-Ctrough Up to safety follow up visit, approx. 35 days post-treatment Trough concentration of DB-1303
Phase 1 & Phase 2: Pharmacokinetic-AUC Up to safety follow up visit, approx. 35 days post-treatment Area under the concentration-time curve from time 0 to infinity of DB-1303
Phase 1 & Phase 2: Pharmacokinetic-Cmax Up to safety follow up visit, approx. 35 days post-treatment Maximum observed plasma concentration (Cmax) of DB-1303
Phase 1 & Phase 2: Pharmacodynamics-ADA Up to safety follow up visit, approx. 35 days post-treatment Data gathered from blood to determine Levels of anti-drug antibody (ADA) against DB 1303 in serum compared to baseline.
Phase 2: Percent change in target lesions as assessed by RECIST 1.1 Up to follow-up period, approximately 1 year post-treatment The percent change in the participant's target lesions from baseline to last study scan using RECIST V1.1
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 Up to follow-up period, approximately 1 year post-treatment The percentage of subjects who had a best response of CR or PR, for Cohort 2b only
To evaluate the safety of DB-1303 with/without ritonavir or itraconazole Up to follow-up period, approximately 1 year post-treatment 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).
Phase 1 & Phase 2: Pharmacokinetic-T1/2 Up to safety follow up visit, approx. 35 days post-treatment Terminal elimination half-life
Phase 1 & 2: Duration of Response (DoR) as assessed by RECIST 1.1 Up to follow-up period, approximately 1 year post-treatment 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
Phase 1 and 2 Cohort b only: Progression-Free Survival Up to follow-up period, approximately 1 year post-treatment Time from subject receiving the first dose to disease progression or death by any cause
Phase 1 & 2: Disease Control Rate (DCR) as assessed by RECIST 1.1 Up to follow-up period, approximately 1 year post-treatment Proportion of participants who had a best response rating of CR or PR, or SD using RECIST V1.1.
Phase 1 and 2 Cohort b only: Overall Survival Up to follow-up period, approximately 1 year post-treatment Time from subject receiving the first dose to death by any cause
Phase I: Percentage of Objective Response Rate (ORR) as assessed by investigator based on 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
Phase 1 & 2: Time to Response (TTR) as assessed by RECIST 1.1 Up to follow-up period, approximately 1 year post-treatment 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
Phase 2: Time on Therapy Up to 21 days after the participant's last dose The duration of time from participant receiving first dose of study drug to the last dose + 21 days
Trial Locations
- Locations (89)
TOI Clinical Research
🇺🇸Cerritos, California, United States
California Research Institute
🇺🇸Los Angeles, California, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
Washington Cancer Institute at MedStar Washington Hospital Center
🇺🇸Washington, District of Columbia, United States
Advanced Research LLC
🇺🇸Coral Springs, Florida, United States
The Oncology Institute of Hope and Innovation
🇺🇸Lakeland, Florida, United States
D&H Cancer Research Center LLC
🇺🇸Margate, Florida, United States
HCA Mercy Hospital
🇺🇸Miami, Florida, United States
BRCR Medical Center Inc.
🇺🇸Tamarac, Florida, United States
Southeastern Regional Medical Center, LLC
🇺🇸Newnan, Georgia, United States
Scroll for more (79 remaining)TOI Clinical Research🇺🇸Cerritos, California, United States