The primary objective of this maintenance therapy study is to identify the maximum tolerated dose (MTD) and/ or recommended Phase 2 dose (RP2D), and evaluate the safety, tolerability, and dose-limiting toxicities (DLTs) of odetiglucan in combination with CDX-1140 in patients with metastatic PDAC with evidence of response or stable disease following a minimum of 16 and no more than 32 weeks of chemotherapy. Up to 45 patients will be enrolled and dosed (30 patients in Part A and 15 in Part B).
This is a multiple institution, open-label, 2-part Phase 1b study to determine the MTD (and/ or RP2D), safety, tolerability, and preliminary efficacy of the combination of odetiglucan and CDX-1140 for the treatment of patients with metastatic PDAC with evidence of response or stable disease during a minimum of 16 and no more than 32 weeks of therapy immediately prior to study enrollment. Part A will identify the MTD and/ or RP2D in two cohorts of patients enrolled per ABA status (Cohort 1=ABA+ and Cohort 2=ABA-) and Part B will assess an alternative dosing regimen of RP2D in an anti-beta glucan antibody ABA+, ABA- or ABA mixed population (ABA+ and ABA-) based on observations in Part A. Product: Odetiglucan and CDX-1140 5 Protocol/Amendment No.: PGG-PAN2111, Amd.0010 Confidential - HiberCell Inc. In Part A, a 3 + 3 de-escalation design will be used to determine the MTD of CDX-1140 when administered in combination with odetiglucan (the starting dose for CDX-1140 is that anticipated to be the recommended phase 2 dose (RP2D) based on prior Phase 1 clinical assessment). Two cohorts of patients will be enrolled (ABA+ and ABA-) and proceed independently through the 3+3 de-escalation assessment; up to 30 patients will be enrolled. The following 2 treatment cohorts will be evaluated for safety, tolerability, and preliminary efficacy: * ABA+: Patients with ABA value ≥20 mcg/mL ABA * ABA-: Patients with ABA value \<20 mcg/mL ABA Both cohorts will initiate at Dose Level 1 and de-escalate to Dose Level -1 based on the respective 21-day DLT period: * Dose Level 1: Odetiglucan 4 mg/kg IV plus CDX-1140 1.5 mg/kg * Dose Level -1: Odetiglucan 4 mg/kg IV plus CDX-1140 0.72 mg/kg Treatment will be administered in 3-week cycles. Odetiglucan will be administered weekly on Days 1, 8, and 15 of each cycle followed \~15-30 minutes later by administration of CDX-1140 1.5 mg/kg or 0.72 mg/kg IV Day 1 of each cycle. Part B, if opened, will enroll up to 15 patients to receive odetiglucan 4 mg/kg plus the CDX-1140 RP2D identified in Part A. As in Part A, treatment will be administered in 3-week cycles, however, both odetiglucan and CDX-1140 will be administered on Day 1 of each cycle (no odetiglucan administration on Days 8 and 15 as in Part A). If the RP2D differs between Cohort 1 and Cohort 2 at the end of Part A, the Sponsor in consult with the SMC, may select a single RP2D to investigate or investigate both RP2Ds. If a larger total enrollment is required, the protocol will be amended to support.
Odetiglucan is a soluble, β-1,3/1,6 glucan isolated from the cell wall of a proprietary Saccharomyces cerevisiae yeast strain. Odetiglucan acts as a Pathogen-Associated Molecular Pattern (PAMP).
A fully human agonist anti-CD40 monoclonal antibody
HonorHealth Research Institute
Scottsdale, Arizona, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
Huntsman Cancer Institute, University of Utah
Salt Lake City, Utah, United States
Maximum Tolerated Dose
Determination of MTD of odetiglucan + CDX-1140
Time frame: Within 24 months of last patient enrolled
Duration of Response
Duration of response following treatment with odetiglucan + CDX-1140
Time frame: Within 24 months of last patient enrolled
Overall Response Rate
ORR per RECIST v1.1 and immune-RECIST (iRECIST) following treatment with odetiglucan + CDX-1140
Time frame: Within 24 months of last patient
Median Progression Free Survival and Progression Free Survival at 6 Months
Median progression free survival and progression free survival at 6 months by RECIST v1.1 following treatment with odetiglucan + CDX-1140
Time frame: Within 36 months of last patient enrolled
Median Overall Survival and Overall Survival at 1 Year
Median OS and OS at 1 year following treatment with odetiglucan + CDX-1140
Time frame: Within 36 months of last patient enrolled
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
5