Source – Alligator Bioscience
On June 26, 2023 the combination of mitazalimab, a novel CD40 monoclonal antibody agonist, with chemotherapy has shown promising results in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), according to interim analysis findings from the Phase II OPTIMIZE-1 study (NCT04888312). The study, conducted by Alligator Bioscience, reported deep tumor responses and established the safety and tolerability profile of the combination therapy in this patient population.
In a previous analysis of 23 patients with mPDAC, 13 individuals achieved an objective response when treated with mitazalimab in combination with leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX). Of these responders, 7 patients (54%) continued to exhibit ongoing responses for more than 10 months, with one patient experiencing a response lasting over 17 months.
The updated results from 57 patients with mPDAC, with a follow-up duration ranging from 2 to 17 months, showed an objective response rate (ORR) of 44%. Additionally, 33% of patients achieved stable disease, resulting in a disease control rate of 77%. The median duration of response (DOR) was 8.7 months with mitazalimab plus mFOLFIRINOX compared to 5.9 months with FOLFIRINOX alone. These findings suggest an immunostimulatory effect of mitazalimab and a potential improvement in progression-free survival (PFS)
“Our OPTIMIZE-1 Phase 2 study has produced another set of very encouraging data to add to the growing body of compelling clinical evidence supporting our lead drug candidate mitazalimab in pancreatic cancer. Especially, we are excited to see that tumor responses continue to develop suggesting a longer benefit for the patients, and we are looking forward to seeing the data from the full cohort mature as the trial progress. With our planned discussions with regulators and the expected top-line readout from OPTIMIZE-1 due at the beginning of next year, we continue to make excellent progress with the clinical development of mitazalimab and its route to market.”
– Søren Bregenholt, CEO of Alligator Bioscience
Dr. Jean-Luc van Laethem from Erasmus University Hospital, Brussels, expressed enthusiasm regarding the consistent response rate observed in OPTIMIZE-1, particularly highlighting the durable responses seen in patients with aggressive disease. The positive results in terms of objective response rate and duration of response, averaging approximately 9 months, provide valuable insights into the efficacy of mitazalimab and support its potential as a therapeutic option for first-line treatment in pancreatic cancer patients.
OPTIMIZE-1 is an ongoing Phase Ib/II clinical trial that aims to enroll at least 70 patients with mPDAC who will receive treatment with mitazalimab in combination with mFOLFIRINOX. The primary endpoint of the study is ORR, with secondary endpoints including adverse events, anti-drug antibodies, pharmacokinetics, anti-tumor activity, PFS, and overall survival. Eligible patients must be 18 years or older, have an ECOG performance status of 0 or 1, measurable disease, a life expectancy of at least 3 months, and acceptable hematologic and clinical laboratory values. Patients should not have received prior chemotherapy for PDAC or abdominal radiotherapy, and certain comorbidities that may interfere with the study treatment are excluded.
“Several compounds have failed to show clinical benefit in pancreatic cancer. These second interim results from OPTIMIZE-1, in which mitazalimab again demonstrates a consistent response rate, together with the durable responses in several patients with extremely aggressive disease is particularly encouraging. The consistent objective response rate together with the positive signal on duration of response of approximately 9 months gives us further crucial insight into the efficacy of mitazalimab and provides more evidence of the potential of this CD40 agonist to be further developed for becoming a therapeutic option for first line pancreatic cancer patients.”
– Prof. Jean-Luc van Laethem, coordinating investigator, Erasmus University Hospital, Brussels (BE)
