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

Purpose

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.

Condition

  • HER2-positive Advanced Solid Tumor

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts 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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • Drug: Pertuzumab Injection
    Administered IV
  • Drug: Ritonavir
    Administered oral
  • Drug: Itraconazole
    Administered oral
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 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
  • Biological: DB-1303/BNT323
    Administered IV
  • Drug: Ritonavir
    Administered oral
  • Drug: Itraconazole
    Administered oral
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
  • Biological: DB-1303/BNT323
    Administered IV
  • Drug: Pertuzumab Injection
    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

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02214

More Details

Status
Recruiting
Sponsor
DualityBio Inc.

Study Contact

Britney Winterberger
+1-513-403-8568
britney.winterberger@tigermedgrp.com

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.