BNT321-02
This trial is designed as a Phase I/randomized Phase II open-label trial of modified(m) FOLFIRINOX ± BNT321 for adjuvant therapy in pancreatic ductal adenocarcinoma (PDAC) patients post R0 or R1 resection.
The Phase I, dose escalation part of this trial will be a limited evaluation of two planned BNT321 dose levels in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks).

Following determination of the combination recommended Phase II dose (RP2D), the Phase II (randomized treatment) part of this trial will be initiated as an open-label 2-arm evaluation of mFOLFIRINOX ± BNT321 (24 weeks) followed by BNT321 monotherapy (24 weeks) in the combination arm only to complete the adjuvant therapy course. Treatment cycles are every 2 weeks (14 days).

The Phase I part of the trial will be a limited dose finding evaluation, whereby a minimal number of BNT321 dose levels will be tested for safety and tolerability in combination with mFOLFIRINOX chemotherapy. Dose escalation will be conducted using a 3+3 design, with up to six additional patients treated at the Phase I defined combination maximum tolerated dose (MTD). Two BNT321 dose levels are initially planned, Dose Level 1 and Dose Level 2. Following evaluation of safety profile for Dose Level 2, additional BNT321 dose levels may be evaluated following safety data review, discussion, and approval by the safety review committee (SRC).
Following completion of the dose escalation Phase I and identification of the RP2D, the trial will proceed to a randomized Phase II part.

The Phase II part will be a 2-arm, randomization of mFOLFIRINOX ± BNT321, with up to 300 patients enrolled to enable a robust statistical evaluation of the trial’s Phase II primary endpoint, i.e., median disease-free survival (mDFS).
Additional evaluations for Phase II will 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.