NCT07070232

A Clinical Study to Test if an Investigational Treatment Called BNT326 is Safe and Potentially Beneficial When Used Alone or in Combination With Other Investigational Treatments Such as BNT327, for People With Advanced Malignant Tumors

A Phase I/II, Open-label, Adaptive Two-part Trial to Evaluate the Safety, Efficacy, Optimal Dose and Pharmacokinetics of BNT326 as Monotherapy and in Combination With Cancer Immunotherapies in Participants With Advanced Solid Tumors

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 980 (estimated)
• Sponsor: BioNTech SE · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with immunotherapeutic agents (Part 2) in participants with histologically or cytologically confirmed solid tumors that are advanced (i.e., either metastatic or recurrent tumors with no further definitive treatment possible) and/or have relapsed/progressed after prior therapy.

Detailed description

Both parts (Part 1 and Part 2) will start enrolling study participants independent of each other. In Part 1, participants with histologically or cytologically confirmed advanced solid tumors will receive BNT326 monotherapy in the following cohorts: * Cohort 1A: Cutaneous melanoma (second-line or higher treatment \[2L+\]). * Cohort 1B: Actionable oncogenic alterations (AGA)-negative non-small cell lung cancer (NSCLC) 2L+. * Cohort 1C: Epithelial growth factor receptor mutated (EGFRm) NSCLC 2L+. * Cohort 1D: Rare melanoma (acral/uveal/mucosal melanoma) 2L+. * Cohort 1E: Other advanced solid tumors 2L+. * Cohort 1F (drug-drug interaction \[DDI\] Cohort): Advanced solid tumors. * Cohort 1G: Cervical cancer 2L+. In Part 2, BNT326 will be studied as monotherapy or in combination with other immunotherapeutic agents. The first combination treatment will be BNT326 with BNT327 (also known as pumitamig, BMS-986545, or PM8002). The following cohorts are planned: * Cohort 2A: BNT326 + pumitamig for cutaneous melanoma 2L+. * Cohort 2B: BNT326 + pumitamig for human epidermal growth factor receptor 2 (HER2)-negative breast cancer 2L+/first line treatment (1L). * Cohort 2C (Optional): BNT326 + pumitamig for cutaneous melanoma first-line or higher treatment (1L+). This cohort may be added if BNT326 + pumitamig for cutaneous melanoma 2L+ is tolerated, and shows signs of efficacy. * Cohort 2D: BNT326 + pumitamig for gastric cancer (GC)/gastroesophageal junction cancer (GEJC) 2L+. * Cohort 2E: BNT326 + pumitamig for colorectal cancer 2L+. * Cohort 2F: BNT326 + pumitamig for cervical cancer 2L+. Participants in Cohorts 1A, 1B, and 1C (dose optimization cohorts) will be randomized to one of two dose levels (DLs) of BNT326 in a 1:1 ratio. In the dose expansion of Cohorts 2A and 2B, participants will be randomized 1:1 to one of two DLs of BNT326 and pumitamig combination treatment. During the randomized dose optimization and contribution of components of Cohorts 2D and 2E, participants will be randomized in a 1:1:1 ratio to one of three treatment arms (BNT326 DL2 or one of two DLs of BNT326 and pumitamig combination treatment). No randomization is planned for Cohorts 1D, 1E, 1F, 1G, 2C and 2F. The study will consist of a screening period, a treatment period, a safety follow-up period, an efficacy follow-up period, and a long-term survival follow-up period. Study treatment will be continued for up to 24 months or until disease progression, withdrawal of consent, termination of the study by the sponsor, or unacceptable toxicity. For each participant, the treatment and follow-up periods are projected to be completed within \~38 months (Part 1) and \~48 months (Part 2), unless participants are continuing to benefit from treatment per investigator's recommendation and upon sponsor approval.

Conditions

• Advanced Solid Tumor

Interventions

Type	Name	Description
DRUG	BNT326	Intravenous (IV) infusion
DRUG	Pumitamig	IV infusion
DRUG	Itraconazole	Oral administration
DRUG	Paroxetine	Oral administration

Timeline

• Start date: 2025-08-12
• Primary completion: 2028-02-01
• Completion: 2029-10-01
• First posted: 2025-07-17
• Last updated: 2026-03-12

Locations

53 sites across 7 countries: United States, Australia, Belgium, Germany, Italy, Spain, United Kingdom

Regulatory

• FDA-regulated drug study