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

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).

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: mFOLFIRINOX; Drug: BNT321 RP2D; Drug: BNT321 0.5 mg/kg; Drug: BNT321 DL 2

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90067
      • Valkyrie Clinical Trials
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina (MUSC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has signed an informed consent form (ICF) before initiation of any study-specific procedures
• Was >18 years or age deemed to be an adult per local authorities inclusive, at the time of giving written informed consent
• Were willing and able to comply with scheduled visits, treatment schedule, laboratory tests, lifestyle restrictions, and other requirements of the study (per investigator assessment, must been capable of understanding and following study-related instructions)
• Had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Had histologically or cytologically confirmed PDAC
• Had macroscopically complete resection (R0 or R1 resection, Royal College of Pathologists [RCP] classification) performed between ≥21 and ≤84 days prior to Cycle 1, Day 1 (C1D1). Submission of formalin-fixed paraffin-embedded tissue (FFPE) tumor tissue from resection or biopsy was required
• Had no radiologic (computed tomography/magnetic resonance imaging) evidence of metastatic disease, malignant ascites, or pleural effusion through an assessment obtained within 4 weeks of first study medication (i.e., C1D1)
• Full recovery from surgery and able to receive chemotherapy
• Had acceptable laboratory parameters
• Was willing to allow collection of pharmacokinetic samples
• Agreed not to enroll in another study of an IMP, starting after signing of the ICF and continuously until the last planned visit in this study
• Participants of childbearing potential (POCBP) must not been pregnant. POCBP, male participants who were sexually active with POCBP, and female partners of male participants should have used a highly effective method of contraception continuously throughout the study and for a period of 111 days after the last dose of BNT321 and for 9 months (POCBP) and 6 months (male participants) after the last oxaliplatin dose
• POCB who agreed not to donate eggs (ova, oocytes) starting after signing of the ICF and continuously throughout the study and for a period of 3 months after the last dose of BNT321 and for 9 months after the last oxaliplatin dose
• Men who were willing to refrain from sperm donation, starting after signing of ICF and continuously throughout the study until 111 days after receiving the last dose of BNT321 and for 6 months after the last oxaliplatin dose

Exclusion Criteria:

• Participants were pregnant or breastfeeding or planning pregnancy or to father children during the study or within 60 days after last IMP treatment
• A medical, psychological, or social condition which, in the opinion of the investigator, could have compromised their wellbeing if they participated in the study, or that could have prevented, limited, or confounded the protocol specified assessments or procedures, or that could have impacted adherence to protocol-described requirements
• Had major surgery within 3 weeks of first dose of the study treatment, where participation in the study could have compromised the participant's wellbeing in the opinion of the investigator
• Had abnormal electrocardiograms (ECGs) that were clinically significant, such as Fridericia-corrected QT prolongation >470 msec (for women) and >450 msec (for men), (average of three ECGs at least 5 minutes apart)
• Had a history of anaphylactic reaction to human, or humanized, antibody
• Have had other known active cancer(s) likely to require treatment in the next 2 years
• Had prior radiotherapy or systemic treatment for PDAC
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic antiinfective therapy that has been administered less than 2 weeks prior to the first dose of BNT321
• Known hypersensitivity to any of the excipients of the experimental product BNT321
• Known history of seropositivity for human immunodeficiency virus (HIV) with CD4+ T-cell counts <350 cells/μL and with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections
• Known history/positive serology for Hepatitis B requiring active antiviral therapy (unless immune due to vaccination or resolved natural infection or unless passive immunization due to immunoglobulin therapy; participants with positive serology must have had Hepatitis B virus viral load below the limit of quantification)
• Active Hepatitis C virus infection (participants who have had completed curative antiviral treatment with Hepatitis C virus viral load below the limit of quantification were allowed)
• Use of any IMP or device within 21 days before administration of first dose of study treatment or ongoing participation in the active treatment phase of another interventional clinical study
• Was subject to exclusion periods from another investigational study
• Were vulnerable individuals as per ICH E6 definition, i.e., individuals whose willingness to participate in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.
• Serum CA19-9 >180 U/mL within 3 weeks of C1D1
• Incomplete macroscopic tumor removal (R2 resection)
• Significant cardiovascular risk (past medical history of coronary stenting or myocardial infarction within 6 months, or New York Heart Association (NYHA) Class III/IV, heart failure, or concurrent unstable angina) or risk factors for QT prolongation (sustained Grade 3 or higher hypokalemia, history of unstable arrhythmia or family history of long QT syndrome)
• Pre-existing neuropathy
• Homozygous UDP glucuronosyltransferase family 1 member A1 (UGT1A1)*28 mutation, if testing was required by local regulations
• Inflammatory disease of the colon or rectum, or occlusion or sub-occlusion of the intestine or severe post-operative uncontrolled diarrhea
• Complete dihydropyrimidine dehydrogenase deficiency, if testing was required by local regulations
• Received a live vaccine within 3 weeks prior to the first dose of study treatment
• Participants with a contraindication to receiving mFOLFIRINOX
• Participants with active or latent tuberculosis or history of Mycobacterium tuberculosis infection currently or within the last 2 years
• Individuals committed to an institution by virtue of an order issued either by the judicial or the administrative authorities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 2 - BNT321 RP2D + mFOLFIRINOX; BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)	Drug: mFOLFIRINOX; Intravenous infusion; Drug: BNT321 RP2D; Intravenous infusion
Active Comparator: Phase 2 - mFOLFIRINOX; mFOLFIRINOX chemotherapy (24 weeks) as monotherapy	Drug: mFOLFIRINOX; Intravenous infusion
Experimental: Phase 1 - BNT321 0.5 mg/kg + mFOLFIRINOX; BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)	Drug: mFOLFIRINOX; Intravenous infusion; Drug: BNT321 0.5 mg/kg; Intravenous infusion
Experimental: Phase 1 - BNT321 DL 2 + mFOLFIRINOX; BNT321 in combination with mFOLFIRINOX chemotherapy (24 weeks) followed by BNT321 monotherapy (24 weeks)	Drug: mFOLFIRINOX; Intravenous infusion; Drug: BNT321 DL 2; Intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - The Number and Percentage of Participants With at Least One Dose of Investigational Medicinal Product (IMP) Reporting Treatment Emergent Adverse Events (TEAEs)	TEAEs graded per Common Toxicity Criteria for Adverse Events version 5.0 (CTCAE v5.0), including Grade ≥3, serious, fatal TEAE by relationship.	from the start of study drug treatment until the end of study (i.e., 164 days)
Phase 1 - The Number and Percentage of Participants With at Least One Dose of IMP Reporting Occurrence of Dose Limiting Toxicities (DLTs)	For all Phase I cohorts the DLT assessment period was planned to encompass the treatment cycles of the first two consecutive BNT321 doses, i.e., 28 days within treatment Cycles 2 and 3. To be considered a DLT, an AE must have met the following three criteria: Occurred during the DLT assessment period of BNT321.; Was considered BNT321-related (i.e., definitely related or possibly related).; Occurred in the presence of adequate supportive care (e.g., Grade 3 vomiting despite use of an appropriate anti-emetic regimen). In addition, to be considered a DLT, an AE must have met at least one of the additional criteria using CTCAE v5.0 as specified in the protocol.	up to 28 days after first dose of BNT321
Phase 2 - Disease-free Survival (DFS)	DFS was 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.	up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 and 2 - OS	OS was defined as the time from first dose of study treatment to death from any cause.	up to 60 months
Phase 1 and 2 - Relapsed Free Survival (RFS)	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.	up to 60 months
Phase 1 and 2 - PK Assessments: Mean Area Under the Curve (AUC) Values Derived From Serum Concentration of IMP	Mean AUC from participants 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 study (EOT).	up to 48 weeks
Phase 1 and 2 - PK Assessments: Mean Observed Maximum Concentration (Cmax) Derived From Serum Concentration of IMP	Mean Cmax from participants 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.	up to 48 weeks
Phase 1 and 2 - PK Assessments: Median Time to Reach Cmax (Tmax) Derived From Serum Concentration of IMP	Median tmax from participants 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.	up to 48 weeks
Phase 1 and 2 - Percentage of Participants With Detectable Anti-drug Antibody (ADA)	Percentage of participants 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	up to 48 weeks
Phase 1 and 2 - Percentage of Participants With Detectable and Durable ADCC and/or CDC Activity	Percentage of participants who are dosed with at least one dose of IMP with detectable and durable (measurable throughout time on study) ADCC and/or CDC activity in Cycles 2 and 4, followed by sparse sampling through EOT	up to 48 weeks
Phase 1 and 2 - Change From Baseline for Participant-reported Health-related Quality of Life (HRQoL) Using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30)	Change from baseline at end of Cycle 12 for participant-reported HRQoL using EORTC QLQ-C30	up to 60 months
Phase 1 and 2 - Change From Baseline for Participant-reported HRQoL Using EORTC Quality of Life Questionnaire for Pancreatic Cancer (QLQ-Pan26) Questionnaires	Change from baseline at end of Cycle 12 for participant-reported HRQoL using EORTC QLQ-Pan26 questionnaires	up to 60 months
Phase 1 and 2 - Change From Baseline in Combined Item Scores From EORTC QLQ-C30	Change from baseline at end of Cycle 12 in combined item scores from EORTC QLQ-C30	up to 60 months
Phase 1 and 2 - Change From Baseline in Combined Item Scores From EORTC QLQ-Pan26	Change from baseline at end of Cycle 12 in combined item scores from EORTC QLQ-Pan26.	up to 60 months
Phase 2 - Occurrence of TEAEs Including Grade ≥3, Serious, Fatal TEAE by Relationship		up to 12 months
Phase 2 - Occurrence of Dose Reduction and Discontinuation of IMP Due to TEAE	Occurrence within a participant.	up to 12 months
Phase 2 - Occurrence of Abnormal Laboratory Parameters	Occurrence within a participant.	up to 48 weeks

Collaborators and Investigators

• Sponsor: BioNTech SE
• Investigators: Study Director: BioNTech Responsible Person, BioNTech SE

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2024
• Primary Completion (Actual): September 18, 2024
• Study Completion (Actual): September 18, 2024

Study Registration Dates

• First Submitted: September 11, 2023
• First Submitted That Met QC Criteria: September 29, 2023
• First Posted (Actual): October 6, 2023

Study Record Updates

• Last Update Posted (Estimated): October 31, 2025
• Last Update Submitted That Met QC Criteria: October 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: CA19-9 Positive Malignancies; Pancreatic Cancer and other CA19-9 expressing malignancies; Pancreatic Ductal Adenocarcinoma (PDAC); Sialyl Lewis A (sLea)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: BNT321-02; 2023-506014-47 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No