Safety and Preliminary Effectiveness of BNT317, an Investigational Therapy for Advanced Solid Tumors

The study will consist of four parts, Part A, Part B1, Part B2 and Part B3.

Part A will be a dose escalation part to investigate the safety and tolerability of BNT317 in participants with advanced solid tumors and may enroll additional participants with advanced solid tumors to specific dose levels (DLs), based on the emerging safety, PK, and pharmacodynamic data. Part A will evaluate up to six DLs of BNT317 monotherapy.

Part B will include dose optimization and dose expansion components to further investigate the safety and tolerability of BNT317 and to investigate preliminary antitumor activity, i.e.:

* Part B1 will further evaluate BNT317 monotherapy in participants with second-line of therapy or higher (2L+) clear cell renal cell carcinoma (ccRCC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B2 will further evaluate BNT317 when added to standard of care (SoC) treatment in participants with 2L+ human epidermal growth factor receptor 2 (HER2)-negative gastric cancer (GC)/gastroesophageal junction cancer (GEJC). Participants will be randomized 1:1 into two dose groups which will evaluate two DLs (as selected from Part A). * Part B3 will further evaluate BNT317 when added to SoC treatment in participants with 2L+ actionable genomic alteration (AGA)-negative non-small cell lung cancer (NSCLC) at the higher of the two BNT317 dose groups being investigated in Parts B1 and B2.

Participants may receive investigational medicinal product (IMP) for up to 2 years or until they experience disease progression, unacceptable toxicities, withdrawal of consent, study discontinuation or investigator decision. The total duration of the study for a single participant may be up to 2 years, plus follow-up until the last participant has completed 1 year of survival follow-up (excluding screening).

In Part A (dose escalation), an accelerated titration design for DL1 and a Bayesian Optimal Interval (BOIN) design for dose groups DL2 and above will be used to evaluate dose limiting toxicities (DLTs).

Additional dosing schedules and/or intermediate or higher DLs may be evaluated based on the available safety, antitumor activity, PK, and pharmacodynamic data.