DB-1303-O-1001
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
Trial summary:
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.
Receptor status / problem studied:
Inclusion criteria
1) 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.
2) At least 1 measurable lesion (per RECIST 1.1).
3) Provide signed informed consent.
4) ECOG performance status (PS) of 0-1.
5) LVEF ≥ 50% by ECHO or MUGA.
6) Adequate organ functions.
7) Provide pre-existing diagnosis of HER2 status or resected tumor samples or undergo fresh tumor biopsy for HER2 testing.
8) Life expectancy of ≥ 3 months.
Additional Inclusion Criteria for Part 2 Expansion Group 9:
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.
Exclusion criteria
1) History of symptomatic CHF (New York Heart Association [NYHA] classes II-IV) or serious cardiac arrhythmia requiring treatment.
2) History of myocardial infarction or unstable angina within 6 months before Day 1.
3) Average QTcF > 450 ms in males and > 470 ms in females.
4) History of clinically significant lung diseases.
5) Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals.
6) HIV infection with AIDS defining illness or active viral hepatitis.
7) Clinically active brain metastases.
8) Unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0, Grade ≤ 1 or baseline.
9) A known hypersensitivity to either the drug substances or inactive ingredients in the drug product.
10) 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.
Trial Title
DB-1303-O-1001
Diagnosis
Advanced solid tumours
Type of trial
Pharmaceutical
Type of treatement
Medical Oncology
Phase
I/II