Mitazalimab and Modified FOLFIRINOX Garners Responses in Metastatic PDAC Phase 2 Trial

Mitazalimab and Modified FOLFIRINOX Garners Responses in Metastatic PDAC Phase 2 Trial

Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) continued to achieve responses following frontline treatment with the combination of the CD40-directed monoclonal antibody agonist mitazalimab and modified FOLFIRINOX (mFOLFIRINOX), in a follow-up from the phase 2 OPTIMIZE-1 trial (NCT04888312).¹

Findings from the second interim analysis for patients included in the futility analysis cohort (n = 23) showed that the combination elicited an objective response rate (ORR) of 57%. Among 13 responders, 7 patients (54%) were receiving ongoing treatment for more than 10 months, with 1 patient receiving treatment for 17 months. Follow-up for this group ranged from 9 to 17 months.

An interim analysis conducted for all evaluable patients in OPTIMIZE-1 (n = 57) showed that at a follow-up ranging from 2 to 17 months, the ORR was 44%. Additionally, 33% of patients experienced stable disease, resulting in a disease control rate of 77%. The median duration of response (DOR) was 8.7 months.

“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,” Jean-Luc van Laethem, MD, PhD, coordinating principal investigator, Erasmus University Hospital, Brussels, stated in a news 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.”

Prior data from the first interim analysis for patients in the futility analysis cohort demonstrated that the ORR was 52%.² In May 2023, mitazalimab received an orphan drug designation from the FDA for use as a potential therapeutic option in patients with pancreatic cancer.³

The open-label, single-arm study enrolled previously untreated patients who were at least 18 years of age with histologically documented metastatic PDAC. Patients were required to have measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 or 1, adequate hematologic levels, and a life expectancy of at least 3 months. Prior chemotherapy for PDAC was not allowed, and prior abdominal radiotherapy was not permitted, except for palliative radiotherapy for non-target lesions.⁴

Key exclusion criteria included other types of non-ductal pancreatic tumors, known central nervous system metastases or carcinomatous meningitis, or a contraindication to mitazalimab or applicable chemotherapy.

Mitazalimab was given intravenously once every 14 days in combination with mFOLFIRINOX. During the phase 1b portion of the study, mitazalimab was given at a dose of 450 µg/kg or 900 µg/kg, and 900 µg/kg was established as the recommended phase 2 dose.⁵

In phase 2, ORR served as the trial’s primary end point. Secondary end points included best overall response, DOR, DCR, progression-free survival, overall survival, and safety.

The updated analysis confirmed the manageable safety and tolerability profile of mitazalimab plus mFOLFIRINOX, according to the announcement from Alligator Bioscience.¹ Prior safety data presented at the 2023 ASCO Annual Meeting for evaluable patients treated with mitazalimab at 900 µg/kg (n = 38) showed that the most common grade 3 or higher adverse effects reported in at least 5% of patients included neutropenia (18.4%), fatigue (13.2%), thrombocytopenia (10.5%), hypokalemia (10.5%), anemia (7.9%), diarrhea (7.9%), vomiting (5.3%), and pneumonia (5.3%).⁵

“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[es],” Søren Bregenholt, chief executive officer of Alligator Bioscience, stated in a news 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 June 27, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-announces-positive-second-interim-efficacy-analysis
2. Alligator Bioscience announces positive interim results from mitazalimab OPTIMIZE-1 phase 2 trial in pancreatic cancer exceeding 50% objective response rate. News release. Alligator Bioscience. January 2, 2023. Accessed June 27, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-announces-positive-interim-results
3. Alligator Bioscience receives FDA orphan drug designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. May 18, 2023. Accessed June 27, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-receives-fda-orphan-drug-designation-for-mitazalimab-in-pancreatic-cancer/
4. 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
5. Prenen H, Borbath I, Geboes KP, et al. Efficacy and safety of mitazalimab in combination with mFOLFIRINOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): an interim analysis of the optimize-1 phase 1b/2 study. J Clin Oncol. 2023;41(suppl 16):4139. doi:10.1200/JCO.2023.41.16_suppl.4139