NCT06069778

Safety, Tolerability, and Efficacy of mFOLFIRINOX ± BNT321 as Adjuvant Therapy Following Curative Resection in Patients With Pancreatic Adenocarcinoma

A Phase I/Randomized Phase II, Open-label Multicenter Trial to Evaluate the Safety, Tolerability, and Efficacy of mFOLFIRINOX With or Without BNT321 as Adjuvant Therapy Following Curative Resection in Patients With Pancreatic Adenocarcinoma

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

Summary

This study was designed as a Phase 1/randomized Phase 2 open-label study of modified(m) FOLFIRINOX ± BNT321 for adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC) patients post R0 or R1 resection. The Phase 1, dose escalation part of this study was planned to be a limited evaluation of two planned BNT321 dose levels (DLs) in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks). Following completion of the dose escalation Phase 1 and identification of the recommended Phase 2 dose (RP2D), the study was designed as a 2-arm, randomized Phase 2 of mFOLFIRINOX ± BNT321 to evaluate the efficacy of mFOLFIRINOX + BNT321 versus mFOLFIRINOX alone as adjuvant therapy in PDAC patients post R0 or R1 resection. Treatment cycles were every 2 weeks (14 days).

Detailed description

The Phase 1 part of the study was planned to be a limited dose finding evaluation, whereby a minimal number of BNT321 DLs were planned to be tested for safety and tolerability in combination with mFOLFIRINOX chemotherapy. Dose escalation was planned to be conducted using a 3+3 design, with up to six additional participants treated at the Phase 1 defined combination maximum tolerated dose (MTD). Two BNT321 DLs were initially planned, 0.5 mg/kg and a second DL 2. Following evaluation of safety profile for DL 2, additional BNT321 DLs could have been evaluated following safety data review, discussion, and approval by the safety review committee (SRC), and health authority review and approval. Approximately 20 participants were planned to be enrolled into the Phase 1 part. Following completion of the dose escalation Phase 1 and identification of the RP2D, the study was planned to proceed to a randomized Phase 2 part. For this part, an independent data monitoring committee was planned to be be established prior to the inclusion of the first participant in this phase. The randomized Phase 2 was designed to enroll up to 300 participants to enable a robust statistical evaluation of the study's Phase 2 primary endpoint, i.e., median disease-free survival (mDFS). Additional evaluations for Phase 2 were planned to include determination of combination regimen safety and tolerability, determination of overall survival (OS), pharmacokinetic (PK), and pharmacodynamic (PD) analyses including anti-drug antibody (ADA), complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) assessments, cytokine and circulating tumor DNA (ctDNA) assessments. The study was terminated early by the sponsor due to strategic reprioritization and not due to safety concerns. At the time of the termination, only one dose level (i.e., 0.5 mg/kg) of BNT321 was tested.

Conditions

• Pancreatic Cancer

Interventions

Type	Name	Description
DRUG	BNT321 0.5 mg/kg	Intravenous infusion
DRUG	BNT321 DL 2	Intravenous infusion
DRUG	mFOLFIRINOX	Intravenous infusion
DRUG	BNT321 RP2D	Intravenous infusion

Timeline

• Start date: 2024-03-27
• Primary completion: 2024-09-18
• Completion: 2024-09-18
• First posted: 2023-10-06
• Last updated: 2025-10-31
• Results posted: 2025-10-31

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study