A Phase II, Multi-site, Randomized, Open-label, Trial of BNT327 in Combination With Chemotherapy in Patients With Metastatic Pancreatic Cancer
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- BioNTech SE
- Enrollment
- 105
- Locations
- 10
- Primary Endpoint
- Confirmed overall response rate
Overview
Brief Summary
This study will enroll adults with confirmed metastatic pancreatic ductal adenocarcinoma (PDAC, systemic PDAC treatment naïve), Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, and adequate organ function. Participants will receive pumitamig (BNT327) in combination with chemotherapy.
Detailed Description
Participants will be assigned to treatment arms with modified (m) FOLFIRINOX administration (Treatment Arms 1 and 2) or the treatment arm with nab-paclitaxel + gemcitabine administration (Treatment Arm 3) based on the physician's choice of chemotherapy. Study participants assigned to arms with mFOLFIRINOX administration, will be randomized 1:1 to one of the two arms (Treatment Arms 1 or 2). Once enrollment of Treatment Arms 1 to 3 has been completed, enrollment into the exploratory cohorts (Treatment Arms 4A and 4B) will be opened.
There will be a screening period of up to 28 days, followed by a treatment period lasting up to 2 years. After administration of the last dose of study treatment, participants will be followed-up for safety for up to 90 days or until the participant initiates new anticancer treatment (e.g., systemic, radiotherapy/surgery). Thereafter, survival follow-up will be conducted until the participant dies or withdraws consent for survival status follow-up, loss of contact, or study termination (whichever occurs first).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have a histologically or cytologically confirmed metastatic PDAC. A tissue sample, archival or fresh, must be provided during the screening period. In case it is not feasible to meet the required tumor tissue criteria, approval by the sponsor's medical monitor is needed for enrollment.
- •Have not received prior systemic therapy for unresectable metastatic PDAC. For participants who have received prior induction chemotherapy, concurrent chemoradiotherapy, or adjuvant/neoadjuvant chemotherapy for curative-intent, the interval should be at least 6 months from the end of the last treatment to relapse.
- •Have at least one measurable lesion as the targeted lesion based on RECIST v1.
- •Lesions treated after prior local treatment (radiotherapy, ablation, interventional procedures) are not considered as target lesions. If the lesion with prior local treatment is the only targeted lesion, evidence-based radiology must be provided to demonstrate disease progression (the single bone metastasis or the single central nervous system \[CNS\] metastasis should not be considered as a measurable lesion).
- •Agree to discontinue strong inhibitors or inducers of cytochrome P450 enzyme (CYP3A), CYP2C8, glucuronosyltransferase 1 family, polypeptide A cluster 1A (UGT1A1) at least 2 weeks prior to starting study treatment, and change to other treatment regimens at screening if such drugs are used.
Exclusion Criteria
- •Have received any of the following therapies or drugs before study enrollment:
- •Have received prior systemic anticancer therapy for unresectable metastasis disease.
- •Any anticancer therapy, including systemic, palliative, biologic, immunostimulatory, or immunosuppressive treatment within 4 weeks (or five half-lives, whichever is longer) before starting study treatment.
- •PD(L)-1/VEGF bispecific antibody, including monotherapy with either category or combinations thereof.
- •Systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 14 days before starting study treatment. Exception: Excluding local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short-term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergies) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens).
- •Vaccinations with live attenuated vaccine(s) within 4 weeks before starting study treatment.
- •Broad-spectrum intravenous antibiotics therapy within 2 weeks before starting study treatment.
- •Any non-study investigational medicinal product within five half-lives of the first dose or within 4 weeks, whichever is longer, before initiation of study treatment in this study or ongoing participation in the active treatment phase of another interventional clinical study.
- •Antiplatelet drugs, such as aspirin (\>325 mg/day), clopidogrel (\>75 mg/day), dipyridamole, ticlopidine or cilostazol, etc., within 10 days before starting study treatment to avoid inclusion of participants who have used platelet aggregation inhibitors before the study.
- •Have undergone major organ surgery (core needle biopsies are allowed \>7 days before starting study treatment), open biopsy, significant trauma, or invasive dental procedures (such as dental implants) within 28 days before starting study treatment, or a planned/anticipated need for major surgery during the study treatment period. Placement of vascular infusion devices is allowed. Note: If participant has had major surgery, they must have recovered adequately from the toxicity and/or complications from the treatment before starting study treatment.
Arms & Interventions
Arm 2: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Pumitamig (Drug)
Arm 2: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: mFOLFIRINOX (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Pumitamig (Drug)
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Pumitamig (Drug)
Arm 4B (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen
Intervention: Pumitamig (Drug)
Arm 4B (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen
Intervention: mFOLFIRINOX (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Gemcitabine (Drug)
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Gemcitabine (Drug)
Arm 3: Pumitamig (dose level 2) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Nab-paclitaxel (Drug)
Arm 4A (exploratory): Pumitamig (dose level 2) + treatment of physician's choice chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Nab-paclitaxel (Drug)
Arm 1: Pumitamig (dose level 1) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: mFOLFIRINOX (Drug)
Arm 1: Pumitamig (dose level 1) + chemotherapy
Participants will be administered pumitamig plus chemotherapy regimen.
Intervention: Pumitamig (Drug)
Outcomes
Primary Outcomes
Confirmed overall response rate
Time Frame: Up to 24 months
For each treatment arm. Defined as the percentage of study participants in whom a confirmed complete response (CR) or confirmed partial response (PR) (assessed by the investigator per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST v1.1\]) is observed as best overall response.
Occurrence of treatment emergent adverse events (TEAEs) by severity
Time Frame: From the first dose of study treatment until 90 days after the last dose of study treatment (up to 32 months).
According to (US National Cancer Institute) Common Terminology Criteria for Adverse Events version 5.0 \[CTCAE v5.0\]). By relationship and for each treatment arm.
Occurrence of dose interruptions, reductions, and discontinuations due to TEAEs
Time Frame: Up to 24 months after first dose
For each treatment arm.
Secondary Outcomes
- Disease control rate(Up to 24 months)
- Duration of response(Up to 30 months)
- Progression free survival(Up to 32 months)
- Overall survival(Up to 32 months)
- Pharmacokinetic (PK) assessment: Maximum concentration (Cmax) derived from serum concentration of pumitamig(Up to 6 months from first dose of study treatment)
- PK assessment: Minimum concentration (Cmin) derived from serum concentration of pumitamig(Up to 6 months from first dose of study treatment)
- Incidence of detectable pumitamig anti-drug antibodies in serum(Up to 32 months)