European Medicines Agency Grants Orphan Drug Designation to Mitazalimab for Pancreatic Cancer

Søren Bregenholt

The European Medicines Agency has granted orphan drug designation to mitazalimab for use in patients with pancreatic cancer, according to a recent announcement from Alligator Bioscience.¹

The CD40-directed monoclonal antibody is under investigation in the phase 2 OPTIMIZE-1 trial (NCT04888312), where it is being paired with modified FOLFIRINOX (fluorouracil, leucovorin, irinotecan, and oxaliplatin) in the frontline treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC).²

Data from the second interim analysis of the trial showed that in those who comprised the futility cohort (n = 23), the combination induced an objective response rate (ORR) of 57%. Of the 13 patients who experienced response, 54% received treatment for longer than 10 months and 1 received treatment for 17 months. The follow-up time ranged from 9 to 17 months.²

Moreover, at a follow-up time ranging from 2 to 17 months, the addition of mitazalimab to mFOLFIRINOX resulted in an ORR of 44% for all evaluable patients (n = 57). The disease control rate (DCR) in this group was 77%, and the median duration of response (DOR) was 8.7 months by RECIST v1.1 criteria.²

“We are very pleased that the European Medicines Agency has granted orphan designation to our lead asset mitazalimab in the treatment of pancreatic cancer,” Søren Bregenholt, chief executive officer of Alligator Bioscience, stated in a press release.¹

Patients with previously untreated histologically documented metastatic PDAC and measurable disease by RECIST v1.1 criteria were enrolled to OPTIMIZE-1.³ Patients needed to be at least 18 years of age, an ECOG performance status of 0 to 1, acceptable hematologic levels, and a life expectancy of at least 3 months. Previous chemotherapy or abdominal radiotherapy was not allowed.

Those with other types of non-ductal pancreatic tumors, known central nervous system metastases or carcinomatous meningitis, or a contraindication to mitazalimab or applicable chemotherapy, were excluded.

Study participants were given intravenous mitazalimab once every 2 weeks in combination with mFOLFIRINOX. In the phase 1b portion of the research, the monoclonal antibody was administered at 450 µg/kg or 900 µg/kg and the latter dose was determined to be the recommended phase 2 dose of the agent.

The primary end point of the trial’s phase 2 portion was ORR, and secondary end points comprised best overall response, DOR, DCR, time to next anticancer therapy, safety, and pharmacokinetics.⁴ Pharmacodynamic biomarkers will be assessed as an exploratory end point.

Previous findings from the first interim analysis of the trial showed that at a median follow-up of about 6 months and at a data cutoff date of December 8, 2023, the combination induced an ORR of 52% in the 23 patients who received mitazalimab at 900 µg/kg and mFOLFIRINOX.

A total of 43 patients received mFOLFIRINOX and mitazalimab at 450 µg/kg (n = 5) and 900 µg/kg (n = 38) and they were examined for safety. Overall, the combination was determined to have a manageable safety profile, with no new safety signals reported. Grade 3 or higher adverse effects (AEs) were experienced by 15.8% of patients.

In the group of patients who received mitazalimab at 900 µg/kg (n = 38), the most common grade 3 or higher AEs occurred 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%).

Treatment-emergent AEs led to treatment discontinuation in 5 patients; these patients experienced pneumonia, gastric obstruction, neuropathy, bacteremia, and altered general condition.

In May 2023, the FDA granted an orphan drug designation to mitazalimab for the same patient population.⁵

“It is our second orphan designation this year following the FDA’s decision to grant us ODD in May, meaning mitazalimab now has stronger commercial protection through market exclusivity in these 2 key markets,” Bregenholt added.¹ “This latest designation adds to the momentum we are building in our efforts to bring this promising drug candidate to market.”

Alligator Bioscience shared that OPTIMIZE-1 is “on track for a topline read out” in the first quarter of 2024.

References

1. Alligator Bioscience receives European Medicine Agency orphan designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. August 21, 2023. Accessed August 25, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-receives-european-medicine-agency-orphan-designation-for-mitazalimab-in-pancreatic-cancer/
2. 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 August 25, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-announces-positive-second-interim-efficacy-analysis
3. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated April 24, 2023. Accessed August 25, 2023. https://clinicaltrials.gov/ct2/show/NCT04888312
4. 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
5. Alligator Bioscience receives FDA orphan drug designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. May 18, 2023. Accessed August 25, 2023. https://alligatorbioscience.se/en/news/alligator-bioscience-receives-fda-orphan-drug-designation-for-mitazalimab-in-pancreatic-cancer/