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BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)

mFOLFIRINOX chemotherapy (24 weeks) as monotherapy

BNT321 Dose Level 1

BNT321 Dose Level 2

mFOLFIRINOX

BNT321 RP2D

BioNTech clinical trials patient information

BioNTech Responsible Person

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.

Radiologists that assess the CT scans will be blinded to the trial treatment.

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

TEAEs including Grade ≥3, serious, fatal TEAE by relationship.

DFS is defined as the time from randomization to occurrence of any of the following events, whichever occurs first:

* Locoregional recurrence or distant metastases as determined by an independent central radiology assessment.
* Occurrence of second primary (same or other) cancer as determined by an independent central radiology assessment.
* Death from any cause.

OS is defined as the time from first dose of trial treatment to death from any cause.

RFS is defined as the time from randomization to occurrence of any of the following events, whichever occurs first:

* Locoregional recurrence or distant metastasis as determined by the investigator.
* Death from any cause.

Mean AUC from patients who are dosed with at least one dose of IMP and who have evaluable PK data in Cycles 2 and 3 followed by sparse sampling through end of trial (EOT).

Mean Cmax from patients who are dosed with at least one dose of IMP and who have evaluable PK data in Cycles 2 and 3 followed by sparse sampling through EOT.

Median tmax from patients who are dosed with at least one dose of IMP and who have evaluable PK data in Cycles 2 and 3 followed by sparse sampling through EOT.

Percentage of patients who are dosed with at least one dose of IMP and with detectable ADA formation in Cycles 1 and 3, followed by sparse sampling through EOT

Percentage of patients who are dosed with at least one dose of IMP with detectable and durable (measurable throughout time on trial) ADCC and/or CDC activity in Cycles 2 and 4, followed by sparse sampling through EOT

Change from baseline at end of Cycle 12 for patient-reported HRQoL using EORTC QLQ-C30

Change from baseline at end of Cycle 12 for patient-reported HRQoL using EORTC QLQ-Pan26 questionnaires

Change from baseline at end of Cycle 12 in combined item scores from EORTC QLQ-C30

Change from baseline at end of Cycle 12 in combined item scores from EORTC QLQ-Pan26.

Spots Global Cancer Trial Database for bnt321 dose level 2