A Clinical Trial to Test if the Investigational Drug BNT3210 is Safe and Potentially Beneficial for People With Advanced Solid Tumors Known to Express the Tumor Marker Sialyl-Tn

This study will consist of two parts (A and B). Part A will be a dose escalation to investigate the safety, tolerability, pharmacokinetics (PK) and preliminarily efficacy of BNT3210. Part B will be a dose optimization and proof-of-concept to further investigate the safety, tolerability and preliminarily anti-tumor activity of BNT3210 at different doses of BNT3210 selected from Part A.

No randomization will be performed in Part A. In Part B, participants will be randomized to different dose levels of BNT3210, as selected from Part A.

• BNT3210 (Drug): Intravenous infusion

Primary outcomes

• Part A only: Occurrence of dose-limiting toxicities (DLTs) during the DLT evaluation period [Up to 21 days from the initiation of first dose of study treatment]: Defined as the first 21 days. By dose level.
• Occurrence of treatment emergent adverse events (TEAEs) by grade, seriousness, and relatedness [Up to approximately 3 years from first dose of study treatment]: From first dose of BNT3210 until 35 days after the last dose of BNT3210 or the start of new anti-cancer treatment, whichever is earlier.
• Occurrence of dose interruptions, reductions, and discontinuation of BNT3210 due to TEAEs [Up to approximately 3 years from first dose of study treatment]: From the time of initiation of the first dose of BNT3210 until administration of the last dose of BNT3210 or the start of new anti-cancer treatment, whichever is earlier.
• Part B only: Objective response rate (ORR) [Up to approximately 3 years from first dose of study treatment]: Defined as the proportion of participants in whom a confirmed complete response (CR) or partial response (PR) (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\] based on the investigator's assessment) is observed as best overall response.

Secondary outcomes

• PK assessment: Area under the curve (AUC) derived from serum concentrations of BNT3210 [Up to approximately 42 days after last dose of study treatment]: By dose level at treatment cycle. If data permits.
• PK assessment: Maximum concentration (Cmax) derived from serum concentrations of BNT3210 [Up to approximately 42 days after last dose of study treatment]: By dose level at treatment cycle. If data permits.
• PK assessment: Time to Cmax (Tmax) derived from serum concentrations of BNT3210 [Up to approximately 42 days after last dose of study treatment]: By dose level at treatment cycle. If data permits.
• PK assessment: Elimination half-life (t1/2) derived from serum concentrations of BNT3210 [Up to approximately 42 days after last dose of study treatment]: By dose level at treatment cycle. If data permits.
• Part A only: ORR [Up to approximately 3 years from first dose of study treatment]: Defined as the proportion of participants in whom a confirmed CR or PR (per RECIST v1.1 based on the investigator's assessment) is observed as best overall response.
• Disease control rate [Up to approximately 3 years from first dose of study treatment]: Defined as the proportion of participants in whom a confirmed CR or PR or stable disease (per RECIST v1.1 based on investigator's assessment) is observed as best overall response.
• Duration of response [Up to approximately 3 years from first dose of study treatment]: Defined as the time from first objective response (CR or PR per RECIST v1.1 based on the investigator's assessment) to first occurrence of objective tumor progression (progressive disease per RECIST v1.1 based on the investigator's assessment) or death from any cause, whichever occurs first.
• Anti-drug antibody (ADA) prevalence [Up to approximately 42 days after last dose of study treatment]: ADA prevalence is defined as the percentage of participants who are ADA positive at any point in time (either baseline or post-baseline).
• ADA incidence [Up to approximately 42 days after last dose of study treatment]: ADA incidence is defined as the proportion of participants having treatment-emergent ADA during the study period.
• Part B only: Progression free survival [Up to approximately 3 years from first dose of study treatment]: Defined as the time from first dose of BNT3210 to first objective tumor progression (progressive disease per RECIST v1.1), or death from any cause, whichever occurs first.
• Part B only: Overall survival [Up to approximately 3 years from first dose of study treatment]: Defined as the time from first dose of BNT3210 to death from any cause.

Sex: All, ages: 18 Years to any

Key Inclusion Criteria:

* Have Eastern Cooperative Oncology Group performance status of 0 to 1.
* Have measurable disease by investigator assessment according to RECIST v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
* Have documented disease progression on or after the prior line of therapy.
* Have an archival formalin-fixed paraffin-embedded tumor tissue sample available or are willing to be biopsied to obtain a fresh tumor tissue sample.
* Have a life expectancy of ≥3 months in the opinion of the investigator.
* Have adequate organ, coagulation, and hematologic function as described in the protocol.
* Have a histologically confirmed advanced/metastatic solid tumor.
* Have no available standard of care therapy likely to confer clinical benefit in the opinion of the investigator. Participants must have received, be intolerant, or refused all available standard therapies.

Key Exclusion Criteria:

* Have had major surgery within the 4 weeks (or 2 weeks for low-invasive cases, e.g., tumor biopsy, puncture) prior to the first dose of study treatment or are planned to undergo major surgery during the course of the study.
* Have had prior allogeneic bone marrow transplantation or solid-organ transplantation.
* Have had an inadequate washout period for prior anti-cancer treatment prior to the first dose of investigational medicinal product (IMP) as defined in the protocol.
* Have received high doses of systemic steroids (>10 mg/day of prednisone or its equivalent) or other immunosuppressive therapy within 2 weeks prior to the first dose of IMP or have a condition requiring high doses of systemic steroids or other immunosuppressive therapy.
* Have received any live attenuated vaccine within 4 weeks prior to the first dose of IMP or intend to receive a live attenuated vaccine during the study.
* Have spinal cord compression, or clinical or radiologic findings indicative of impending cord compression.
* Have a history of (noninfectious) interstitial lung disease (ILD)/pneumonitis that requires steroids, current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening.
* Have an active infection that requires systemic therapy within 2 weeks prior to the first dose of IMP.
* Have any other primary malignancy within 3 years prior to the first dose of IMP.
* Have unresolved toxicities from previous anti-cancer treatment, defined as toxicities (other than alopecia and pigmentation) not yet resolved according to (US) National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0 Grade ≤1.
* Have a history of relevant central nervous system (CNS) pathology or current relevant CNS pathology (e.g., seizure, paresis, aphasia, cerebrovascular ischemia/hemorrhage, severe brain injuries, dementia, Parkinson's disease, epilepsy requiring pharmacologic treatment).
* Have a QT interval corrected by Fridericia's method (QTcF) prolongation to >450 ms if male or >470 ms if female.
* Have, in the opinion of the treating investigator, any concurrent condition(s) that could pose an undue medical hazard or interfere with the interpretation of the study results.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.

• BioNTech Responsible Person, Study director, BioNTech SE