Mitazalimab and Chemotherapy Induces Antitumor Activity in mPDAC

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Treatment with the novel CD40 monoclonal antibody agonist, mitazalimab (formerly ADC-1013), in combination with chemotherapy achieved deep tumor responses in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC), according to interim analysis findings from the phase 2 OPTIMIZE-1 study (NCT04888312).¹

The results, which were reported in a press release by Alligator Bioscience, also established the safety/tolerability profile of the combination in the mPDAC patient population.

Previously in 23 patients with mPDAC, 13 had an objective response to mitazalimab in combination with leucovorin calcium (folinic acid), fluorouracil, irinotecan hydrochloride, and oxaliplatin (mFOLFIRINOX). Responses were ongoing in 7 patients (54%) beyond 10 months. One patient had a response lasting over 17 months.

Updated results came from 57 patients with mPDAC after 2 to 17 months of follow-up. The objective response rate (ORR) was 44%. Responses included stable disease in 33% for a disease control rate of 77%. The median duration of response (DOR) observed was 8.7 months with mitazalimab plus mFOLFIRINOX compared with 5.9 months with FOLFIRINOX alone. This result was indicative of an immunostimulatory effect of mitazalimab and possible improvement in progression-free survival (PFS), according to Alligator Bioscience.

"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," said Jean-Luc van Laethem, MD, PhD, of Erasmus University Hospital, Brussels, in the press release. "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."

OPTIMIZE-1 is a phase 1b/2, open-label, multicenter study with a goal to evaluate at least 70 patients with mPDAC on treatment with mitazalimab combined with mFOLFIRINOX. The study is assessing ORR as its primary end point and the number of patients with adverse events, anti-drug antibodies, pharmacokinetics, anti-tumor activity, PFS, and overall survival as secondary end points.²

Appropriate patients for the study are those aged 18 years or older with an ECOG performance status of 0 or 1, measurable disease, a life expectancy of 3 months minimum, and acceptable hematologic and clinical laboratory values. Patients must have not been previously treated with chemotherapy of PDAC or had abdominal radiotherapy. The study also excludes patients with certain comorbidities that may interfere with study treatment.

"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," said Søren Bregenholt, chief executive officer of Alligator Bioscience, in the press release.¹ “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."

_REFERENCES:

_{1. Alligator Bioscience announces positive second interim efficacy analysis from mitazalimab OPTIMIZE-1 phase 2 study in 1st line pancreatic cancer. News release. Alligator Bioscience. June 26, 2023. Accessed Jun 27, 2023. https://tinyurl.com/2p8w5ebw}

_{2. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated April 24, 2023. Accessed June 27, 2023. https://clinicaltrials.gov/ct2/show/NCT04888312}