Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

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.

BioNTech SE

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Paclitaxel

Gemcitabine

Albumin-Bound Paclitaxel

Immunoglobulins

Folfirinox

Tubulin Modulators

Antimitotic Agents

Antimetabolites

MVT-5873 monotherapy dose escalation, initial to maximum tolerated dose

MVT-5873 is administered in Group B every 1 week in combination with gemcitabine and nab-paclitaxel

MVT-5873 is administered in Group C every 4 weeks by intravenous infusion following a lead in dose. Each cycle is 28 days. During dose escalation, doses of MVT-5873 will be increased to define the MTD. Up to 30 patients will be treated at the RP2D.

MVT-5873 is administered in Group D every 2 weeks by intravenous infusion following a lead in dose. During dose escalation, doses of MVT-5873 will be increased to defined he MTD. Up to 30 patients will be treated at the RP2D.

MVT-5873 is administered in combination with mFOLFIRINOX every 2 weeks. Both MVT-5873 and mFOLFIRINOX will be administered by intravenous infusion. During dose escalation, doses of MVT-5873, will be increased to define the MTD in combination with mFOLFIRINOX. mFOLFIRINOX will be administered according to institutional standards in compliance with the package insert for each drug. Up to 30 patients will be treated at the RP2D.

MVT-5873

modified FOLFIRINOX (mFOLFIRINOX)

gemcitabine + nab-paclitaxel

Erkut Borazanci, MD

Vi Chiu, MD

Judy Wang, MD

Eileen O'Reilly, MD

Meredith Pelster, MD

Phase 1 Safety and Tolerability Study in Subjects with Pancreatic Cancer or Other CA19-9 Positive Malignancies.

Open label, multicenter, non-randomized, dose escalation/expansion trial of MVT-5873 as a single agent and in combination with standard of care chemotherapy or modified FOLFIRINOX (mFOLFIRINOX) in subjects with pancreatic and other CA19-9 positive malignancies. The study will define a Maximum Tolerated Dose (MTD) of MVT-5873 as monotherapy (Group A), in combination with a standard of care chemotherapy (Group B), for a Q2 week schedule (Group D), an MTD of MVT-5873 for a Q4 week schedule (Group C), and an MTD for a Q2 week schedule of MVT-5873 in combination with mFOLFIRINOX (Groups E and F). Each group will utilize a conventional 3+3 study design to identify the MTD and recommended phase 2 dose (RP2D).

Following the definition of an MTD in each group, the RP2D of MVT-5873 as a single agent and in combination with mFOLFIRINOX will be defined. Following the completion of the dose escalation phase for each group, an expansion group of up to 30 additional subjects will be treated at the RP2D for the respective group. In Group D, subjects will be subdivided into two groups of up to 15 subjects: subjects without peripheral blood expression of CA19-9 and subjects with peripheral blood expression of CA19-9. MVT-5873 pharmacokinetics (PK) and pharmacodynamics (PD) will be determined in each group.

Group A, B, and C are no longer open for enrollment.

Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies

Phase 1 Safety and Tolerability Study of Human Monoclonal Antibody 5B1 (MVT-5873) With Expansion in Subjects With Pancreatic Cancer or Other CA19-9 Positive Malignancies

Determined using non-compartmental model.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Safety, Tolerability, and Efficacy of mFOLFIRINOX ± BNT321 as Adjuvant Therapy Following Curative Resection in Patients With Pancreatic Adenocarcinoma	NCT06069778	Pancreatic Canc...	BNT321 Dose Lev... BNT321 Dose Lev... mFOLFIRINOX BNT321 RP2D	18 Years -	BioNTech SE
Study of HuMab-5B1 (MVT-5873) in Subjects With Pancreatic Cancer or Other Cancer Antigen 19-9 (CA19-9) Positive Malignancies	NCT02672917	Pancreatic Canc...	MVT-5873 modified FOLFIR... gemcitabine + n...	18 Years -	BioNTech SE

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