Phase II Trial of DB-1311 in Combination with BNT327 or DB-1305 in Advanced/Metastatic Solid Tumors

The primary objective is to determine the recommended phase 2 dose of DB-1311 in combination with BNT327 and in combination with DB-1305 by assessing safety and tolerability in targeted participant populations. In Part 2, the primary objective also includes evaluation of efficacy and dose optimization for both combinations, which is clinically relevant for defining an appropriate balance between antitumor activity and safety. The secondary objectives are to assess preliminary antitumor activity in Part 1, characterize pharmacokinetics of DB-1311 and its related analytes in both combinations, evaluate immunogenicity, further assess efficacy in Part 2, assess safety in Part 2, and determine the prevalence and incidence of anti-drug antibodies against DB-1311 in serum.

The trial enrolled 307 participants with advanced solid tumors, including non-small cell lung cancer, cervical cancer, melanoma, hepatocellular carcinoma, ovarian cancer, and squamous cell carcinoma of the head and neck. The population included both female and male patients, and adults aged 18 years or older, or the locally accepted minimum age, at the time of informed consent. Participants were selected from targeted participant populations with at least one measurable lesion by RECIST v1.1, an ECOG performance status of 0-1, an expected life expectancy of at least 3 months, adequate organ function, and an appropriate treatment washout period. Additional inclusion criteria included the ability to understand trial requirements and provide written informed consent. Relevant reproductive safety requirements were specified for participants of childbearing potential and fertile males, including pregnancy testing, contraception, and restrictions on egg or sperm donation. No information was provided on diet, physical activity, or other lifestyle habits.

This is a Phase II, multicenter, open-label clinical trial evaluating DB-1311 in combination with BNT327 or DB-1305 in adults with advanced or metastatic solid tumors, including non-small cell lung cancer, cervical cancer, melanoma, hepatocellular carcinoma, ovarian cancer, and squamous cell carcinoma of the head and neck. The study is designed to assess safety, tolerability, pharmacokinetics, immunogenicity, and antitumor activity. In Part 1, the objective is to determine the recommended Phase II dose by evaluating dose-limiting toxicities and treatment-emergent adverse events. In Part 2, efficacy and safety are further assessed, and one randomized dose-optimization arm is used to identify the optimal dose based on safety and efficacy. The overall trial is planned from 2026-05-31 to 2030-06-30. Study participation begins with a screening visit to confirm eligibility, including disease measurability, performance status, organ function, and required washout period. Eligible participants then receive study treatment and undergo follow-up assessments during the treatment period for safety, tumor response, pharmacokinetics, and anti-drug antibodies. An end-of-study visit is performed after completion or discontinuation of treatment to collect final assessments. Expected participant involvement continues through the treatment and assessment period until the end-of-study visit. Early termination may occur for withdrawal of consent, disease progression, unacceptable toxicity, protocol noncompliance, or other investigator-determined reasons.

BNT324 is administered as a powder for concentrate for solution for injection/infusion. It is given by intravenous route at a dose of 00 mg/kg. The trial evaluates this agent as part of combination therapy, and administration is conducted according to the study dosing schedule.

BNT327 is administered as a powder for concentrate for solution for infusion. It is given by intravenous route at a dose of 00 mg/kg. In the trial, it is used as a combination partner with DB-1311, and dosing follows the protocol-defined administration schedule.

BNT325/DB-1305 is a lyophilized powder for solution for infusion. It is given by intravenous route at a dose of 00 mg/kg. In the trial, it is used as a combination partner with DB-1311, and dosing follows the protocol-defined administration schedule.

Objective response rate is the primary efficacy endpoint in Part 2. It is defined as the proportion of participants with a confirmed complete response or partial response as best overall response, based on the investigator’s assessment per RECIST v1.1. Efficacy is also assessed by tumor assessments performed by the investigator per RECIST v1.1 for duration of response, disease-control rate, time to response, and progression-free survival. In participants with platinum-resistant ovarian cancer, CA-125 response rate is assessed per GCIG criteria. Overall survival is also evaluated.

In Part 1, efficacy evaluations include objective response rate, duration of response, disease-control rate, time to response, and progression-free survival, determined from tumor assessments by the investigator per RECIST v1.1. These efficacy endpoints are also evaluated in Part 2, together with overall survival and CA-125 response rate where applicable.