Phase II, open-label, single-arm study of CD40/Dectin-1 immunotherapy as maintenance treatment in patients with unresectable pancreatic ductal adenocarcinoma (PDA) who have not progressed following 4-6 months of first line (1L) chemotherapy.
Phase II, open-label, single-arm study of CD40/Dectin-1 immunotherapy as maintenance treatment in patients with unresectable pancreatic ductal adenocarcinoma (PDA) who have not progressed following 4-6 months of first line (1L) chemotherapy. The protocol incorporates an initial safety run-in phase evaluating dose-limiting (DLTs) over the first 21 days (Cycle 1), followed by a full Phase II efficacy evaluation. The safety run-in will enroll an initial cohort of 3 patients at the recommended Phase 2 dose (RP2D) for both odetiglucan and mitazalimab; if no DLTs occur, the study progresses to full enrollment. If DLTs occur, the cohort will expand to 6 patients with protocol-defined criteria for dose modification or de-escalation. The study includes three treatment cohorts and an observational cohort. Treatment Cohorts: * Cohort A: 26 patients with metastatic PDA achieving partial response (PR) on 1L chemotherapy * Cohort B: 12 patients with metastatic PDA achieving stable disease (SD) on 1L chemotherapy * Cohort C: 12 patients with locally advanced PDA achieving disease stability (PR or SD) on 1L chemotherapy Observational Cohort: An observational cohort of approximately 50-60 patients will be included, divided into three subgroups corresponding to the eligibility criteria of Cohorts A, B, and C: * Observational Subgroup A: 26-30 patients * Observational Subgroup B: 12-15 patients * Observational Subgroup C: 12-15 patients The observational cohort will include patients who meet eligibility criteria but do not receive the study intervention, either due to declining participation in the treatment arm or through retrospective chart review. Total enrollment will be 50 patients in the treatment arm and approximately 50-60 patients in the observational cohort.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Odetiglucan 4 mg/kg IV every 3 weeks
Mitazalimab 0.9 mg/kg IV every 3 weeks
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
RECRUITINGMedian progression-free survival (mPFS) of 7.5 months in Cohort A
The primary endpoint of the trial is median progression-free survival (mPFS) of 7.5 months in Cohort A, defined as the time from treatment initiation to disease progression or death from any cause. PFS will be assessed using imaging per RECIST v1.1 criteria, with analysis conducted using Kaplan-Meier methodology and a log-rank test.
Time frame: 7.5 months
Safety and tolerability of maintenance odetiglucan/mitazalimab
To evaluate safety and tolerability of maintenance odetiglucan/mitazalimab. Safety assessed by CTCAE v5.0 criteria.
Time frame: 19.5 months
Progression-free survival (PFS) in Cohort B
To estimate progression-free survival (PFS) of maintenance odetiglucan/mitazalimab in patients (Cohort B) with metastatic pancreatic adenocarcinoma who achieve stable disease after 4-6 months of 1L chemotherapy.
Time frame: 7.5 months
Progression-free survival (PFS) in Cohort C
To estimate progression-free survival (PFS) of maintenance odetiglucan/mitzalimab in patients (Cohort C) with pancreatic adenocarcinoma but without metastatic disease who achieve either a PR or SD after 4-6 months of 1L chemotherapy
Time frame: 7.5 months
Overall response rate (ORR) (Cohorts A-C)
To estimate efficacy parameters of maintenance odetiglucan/mitazalimab in all patients (Cohorts A-C) by assessing overall response rate (ORR) using RECIST v1.1 and iRECIST
Time frame: 19.5 months
Disease control rate (DCR) (Cohorts A-C)
To estimate efficacy parameters of maintenance odetiglucan/mitazalimab in all patients (Cohorts A-C) by assessing disease control rate (DCR) using RECIST v1.1 and iRECIST
Abramson Cancer Center Clinical Trials Service
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: 19.5 months
Duration of response (DOR) (Cohorts A-C)
To estimate efficacy parameters of maintenance odetiglucan/mitazalimab in all patients (Cohorts A-C) by assessing duration of response (DOR) from first response to progression or death from any cause
Time frame: 19.5 months
Overall survival (OS) (Cohorts A-C)
To estimate efficacy parameters of maintenance odetiglucan/mitazalimab in all patients (Cohorts A-C) by assessing overall survival (OS) from treatment initiation
Time frame: 19.5 months
1-yr Overall survival (OS) rate (Cohorts A-C)
To estimate efficacy parameters of maintenance odetiglucan/mitazalimab in all patients (Cohorts A-C) by assessing 1-yr OS rate
Time frame: 19.5 months
Overall response rate (ORR) between Treatment and Observational Arms
Comparison of ORR between each treatment cohort and their corresponding observational subgroups
Time frame: 19.5 months
Disease control rate (DCR) between Treatment and Observational Arms
Comparison of DCR between each treatment cohort and their corresponding observational subgroups
Time frame: 19.5 months
Duration of response (DOR) between Treatment and Observational Arms
Comparison of DOR between each treatment cohort and their corresponding observational subgroups
Time frame: 19.5 months
Overall survival (OS) between Treatment and Observational Arms
Comparison of OS between each treatment cohort and their corresponding observational subgroups
Time frame: 19.5 months
1-yr Overall survival (OS) rate between Treatment and Observational Arms
Comparison of 1-yr OS between each treatment cohort and their corresponding observational subgroups
Time frame: 19.5 months