Trial Title:
Safety, Tolerability, and Efficacy of mFOLFIRINOX ± BNT321 as Adjuvant Therapy Following Curative Resection in Patients With Pancreatic Adenocarcinoma
NCT ID:
NCT06069778
Condition:
Pancreatic Cancer
Conditions: Official terms:
Adenocarcinoma
Pancreatic Neoplasms
Conditions: Keywords:
CA19-9 Positive Malignancies
Pancreatic Cancer and other CA19-9 expressing malignancies
Pancreatic Ductal Adenocarcinoma (PDAC)
Sialyl Lewis A (sLea)
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
Single (Outcomes Assessor)
Masking description:
Radiologists that assess the CT scans will be blinded to the trial treatment.
Intervention:
Intervention type:
Drug
Intervention name:
BNT321 Dose Level 1
Description:
Intravenous infusion
Arm group label:
Phase 1 - BNT321 Dose Level 1 + mFOLFIRINOX
Intervention type:
Drug
Intervention name:
BNT321 Dose Level 2
Description:
Intravenous infusion
Arm group label:
Phase 1 - BNT321 Dose Level 2 + mFOLFIRINOX
Intervention type:
Drug
Intervention name:
mFOLFIRINOX
Description:
Intravenous infusion
Arm group label:
Phase 1 - BNT321 Dose Level 1 + mFOLFIRINOX
Arm group label:
Phase 1 - BNT321 Dose Level 2 + mFOLFIRINOX
Arm group label:
Phase 2 - BNT321 RP2D + mFOLFIRINOX
Arm group label:
Phase 2 - mFOLFIRINOX
Intervention type:
Drug
Intervention name:
BNT321 RP2D
Description:
Intravenous infusion
Arm group label:
Phase 2 - BNT321 RP2D + mFOLFIRINOX
Summary:
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).
Detailed description:
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), and health authority review and approval.
Approximately 20 patients will be enrolled into the Phase I part.
Following completion of the dose escalation Phase I and identification of the RP2D, the
trial will proceed to a randomized Phase II part. For this part, an independent data
monitoring committee will be established prior to the inclusion of the first patient in
this phase.
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Has signed an informed consent form (ICF) before initiation of any trial-specific
procedures
- Is >18 years or age deemed to be an adult per local authorities inclusive, at the
time of giving written informed consent
- Willing and able to comply with scheduled visits, treatment schedule, laboratory
tests, lifestyle restrictions, and other requirements of the trial (per investigator
assessment, must be capable of understanding and following trial-related
instructions)
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- Has 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 is required
- Has 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 trial medication (i.e., C1D1)
- Full recovery from surgery and able to receive chemotherapy
- Has acceptable laboratory parameters.
- Is willing to allow collection of pharmacokinetic samples
- Agree not to enroll in another trial of an IMP, starting after signing of the ICF
and continuously until the last planned visit in this trial
- Patients of childbearing potential (POCBP) must not be pregnant. POCBP, male
patients who are sexually active with POCBP, and female partners of male patients
should use a highly effective method of contraception continuously throughout the
trial and for a period of 111 days after the last dose of BNT321 and for 9 months
(POCBP) and 6 months (male patients) after the last oxaliplatin dose
- POCB who agree not to donate eggs (ova, oocytes) starting after signing of the ICF
and continuously throughout the trial and for a period of 3 months after the last
dose of BNT321 and for 9 months after the last oxaliplatin dose
- Men who are willing to refrain from sperm donation, starting after signing of ICF
and continuously throughout the trial until 111 days after receiving the last dose
of BNT321 and for 6 months after the last oxaliplatin dose
Exclusion Criteria:
- Patients are pregnant or breastfeeding or planning pregnancy or to father children
during the trial or within 60 days after last IMP treatment
- A medical, psychological, or social condition which, in the opinion of the
investigator, could compromise their wellbeing if they participate in the trial, or
that could prevent, limit, or confound the protocol specified assessments or
procedures, or that could impact adherence to protocol-described requirements
- Had major surgery within 3 weeks of first dose of the trial treatment, where
participation in the trial could compromise the patient's wellbeing in the opinion
of the investigator
- Has abnormal electrocardiograms (ECGs) that are 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)
- Has a history of anaphylactic reaction to human, or humanized, antibody
- Have 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; patients with positive serology must
have Hepatitis B virus viral load below the limit of quantification)
- Active Hepatitis C virus infection (patients who have completed curative antiviral
treatment with Hepatitis C virus viral load below the limit of quantification are
allowed)
- Use of any IMP or device within 21 days before administration of first dose of trial
treatment or ongoing participation in the active treatment phase of another
interventional clinical trial
- Is subject to exclusion periods from another investigational trial
- Are vulnerable individuals as per ICH E6 definition, i.e., individuals whose
willingness to participate in a clinical trial 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 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 required by local
regulations
- Received a live vaccine within 3 weeks prior to the first dose of trial treatment
- Patients with a contraindication to receiving mFOLFIRINOX
- Patients 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Valkyrie Clinical Trials
Address:
City:
Los Angeles
Zip:
90067
Country:
United States
Status:
Recruiting
Facility:
Name:
Clinical Research Alliance
Address:
City:
Westbury
Zip:
11590
Country:
United States
Status:
Recruiting
Facility:
Name:
Prisma Health Cancer Institute
Address:
City:
Greenville
Zip:
29605
Country:
United States
Status:
Recruiting
Start date:
March 27, 2024
Completion date:
June 2031
Lead sponsor:
Agency:
BioNTech SE
Agency class:
Industry
Source:
BioNTech SE
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06069778
