A Phase 1/2a, Multicenter, Open-Label, Non-Randomized First in Human Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of DB-1303 in Patients With Advanced/Metastatic Solid Tumors
Description
This is a multicenter, non-randomized, 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.
Status
Accepting new patients
Primary Study Objective(s)
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Phase 1: Percentage of Participants with Dose-Limiting Toxicities (DLTs) as assessed by CTCAE v5.0.
- Phase 1: Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0.
- Phase 1: Percentage of Participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
- Phase 1: Maximum Tolerated Dose (MTD) of DB-1303
- Phase 1: Recommended Phase 2 Dose (RP2D) of DB-1303
- Phase 2a: Percentage of Participants with Treatment Emergent adverse events (TEAEs) as assessed by CTCAE v5.0.
- Phase 2a: Percentage participants with Serious Adverse Events (SAEs) as assessed by CTCAE v5.0.
- Phase 2a: Percentage of Objective Response Rate (ORR) as assessed by RECIST 1.1.
Core eligibility
Note: This is only a partial list of eligibility criteria.
Inclusion Criteria:
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Has a pathologically documented HER2-positive or HER2-expressing 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.
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.
- 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.
