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

NCT06069778 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: BNT321-022023-506014-47
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Pancreatic Cancer

Keywords

CA19-9 Positive Malignancies; Pancreatic Cancer and other CA19-9 expressing malignancies; Pancreatic Ductal Adenocarcinoma (PDAC); Sialyl Lewis A (sLea)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (14)

• Phase 1 and 2 - OS

  up to 60 months

• Phase 1 and 2 - Relapsed Free Survival (RFS)

  up to 60 months

• Phase 1 and 2 - PK Assessments: Mean Area Under the Curve (AUC) Values Derived From Serum Concentration of IMP

  up to 48 weeks

• Phase 1 and 2 - PK Assessments: Mean Observed Maximum Concentration (Cmax) Derived From Serum Concentration of IMP

  up to 48 weeks

• Phase 1 and 2 - PK Assessments: Median Time to Reach Cmax (Tmax) Derived From Serum Concentration of IMP

  up to 48 weeks

Study Arms (4)

Phase 1 - BNT321 0.5 mg/kg + mFOLFIRINOX

EXPERIMENTAL

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

Drug: BNT321 0.5 mg/kg; Drug: mFOLFIRINOX

Phase 1 - BNT321 DL 2 + mFOLFIRINOX

EXPERIMENTAL

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

Drug: BNT321 DL 2; Drug: mFOLFIRINOX

Phase 2 - BNT321 RP2D + mFOLFIRINOX

EXPERIMENTAL

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

Drug: mFOLFIRINOX; Drug: BNT321 RP2D

Phase 2 - mFOLFIRINOX

ACTIVE COMPARATOR

mFOLFIRINOX chemotherapy (24 weeks) as monotherapy

Drug: mFOLFIRINOX

Interventions

BNT321 0.5 mg/kg DRUG

Intravenous infusion

Phase 1 - BNT321 0.5 mg/kg + mFOLFIRINOX

BNT321 DL 2 DRUG

Intravenous infusion

Phase 1 - BNT321 DL 2 + mFOLFIRINOX

mFOLFIRINOX DRUG

Intravenous infusion

Phase 1 - BNT321 0.5 mg/kg + mFOLFIRINOX; Phase 1 - BNT321 DL 2 + mFOLFIRINOX; Phase 2 - BNT321 RP2D + mFOLFIRINOX; Phase 2 - mFOLFIRINOX

BNT321 RP2D DRUG

Intravenous infusion

Phase 2 - BNT321 RP2D + mFOLFIRINOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• BioNTech SE: lead

Study Sites (2)

Valkyrie Clinical Trials

Los Angeles, California, 90067, United States

Location

Medical University of South Carolina (MUSC)

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: BioNTech clinical trials patient information
• Organization: BioNTech SE

patients@biontech.de

+49 61319084

Study Officials

• BioNTech Responsible Person

  BioNTech SE

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Radiologists that assess the CT scans will be blinded to the study treatment.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2023
• First Posted: October 6, 2023
• Study Start: March 27, 2024
• Primary Completion: September 18, 2024
• Study Completion: September 18, 2024
• Last Updated: October 31, 2025
• Results First Posted: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)