Mitazalimab Plus mFOLFIRINOX Yields 18-Month OS Benefit in Previously Untreated Metastatic Pancreatic Cancer

Søren Bregenholt, PhD, CEO of Alligator Bioscience

Updated results from the phase 2 OPTIMIZE-1 trial (NCT04888312) have shown positive 18-month overall survival (OS) outcomes with the CD40-directed monoclonal antibody mitazalimab plus standard-of-care modified FOLFIRINOX (mFOLFIRINOX) as a frontline treatment for patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to an announcement from drug developer Alligator Bioscience.¹

At a median follow-up of 18.2 months, the OS rate in patients treated with the combination was 36.2%. Moreover, the updated median OS was 14.9 months with the mitazalimab regimen. The median progression-free survival (PFS) was 7.7 months, with a 12-month PFS rate of 35.1%.

Additional data showed that the confirmed overall response rate (ORR) was 42.1% with the addition of a late-responding patient. The unconfirmed ORR was 54.4% among evaluable patients (n = 57), and the median duration of response (DOR) was 12.6 months. At the time of the analysis, a total of 30% patients were still alive, 16% of whom were still on treatment. The longest ongoing duration of treatment was 24 months.

These results compare favorably to the historically reported outcomes with FOLFIRINOX or NALIRIFOX in similar patient populations. Patients treated with FOLFIRINOX alone (n = 171) in a phase 3 trial (NCT00112658) achieved an 18.6% OS rate and a median OS of 11.1 months (95% CI, 9.0-13.1). The 12-month PFS rate was 12.1%, the ORR was 31.6% (95% CI, 24.7%-39.1%), and the median DOR was 5.9 months (95% CI, 4.9-7.1).2 In the phase 3 NAPOLI study (NCT04083235), treatment with NALIRIFOX also produced a median OS of 11.1 months (95% CI, 10.0-12.1) in a similar patient population (n = 383). The investigator-assessed ORR was 41.8% (95% CI, 36.8%-46.9%), and the median DOR was 7.3 months (95% CI, 5.8-7.6).³

“These latest results from the OPTIMIZE-1 study of our lead asset provide a strong validation of the clear and sustained clinical benefit produced by mitazalimab when combined with mFOLFIRINOX in the treatment of [patients with] first-line pancreatic cancer. In fact, mitazalimab increases your chance of being alive at the 18-month mark by 95%, compared to published FOLFIRINOX data,” Søren Bregenholt, chief executive officer of Alligator Bioscience, stated in a press release. “These highly promising outcomes warrant continued clinical development of mitazalimab in a confirmatory setting, and we are committed to bringing mitazalimab to [patients with] pancreatic cancer as fast as possible.”

OPTIMIZE-1 is an open-label, multi-center study evaluating the safety and efficacy of mitazalimab in combination with mFOLFIRINOX in treatment-naive patients with metastatic pancreatic cancer.⁴ The trial enrolled patients at least 18 years of age with histologically documented metastatic PDAC, measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and a life expectancy of at least 3 months. Patients also should not have received prior chemotherapy or abdominal radiotherapy and have adequate hematologic laboratory levels.

The primary end point in the phase 2 portion of the study was ORR. Key secondary end points included PFS, OS, pharmacokinetic parameters, and safety.

Topline results from OPTIMIZE-1 were published in Lancet Oncology and presented at the 2024 ASCO Annual Meeting. Among evaluable patients, mitazalimab plus mFOLFIRINOX produced a median OS of 14.3 months, a median DOR of 12.5 months, and a confirmed ORR of 40.4%, meeting the study’s primary end point.⁵ These data will also be presented at the 2024 ESMO Gastrointestinal Cancers Congress.¹

In January 2023, previously reported data from the first interim analysis of OPTIMIZE-1 were announced, showing that the addition of mitazalimab to mFOLFIRINOX led to an ORR of 52% and disease control rate of more than 90% per RECIST v1.1 in the futility cohort (n = 23).6 That same year, mitazalimab was granted orphan drug designation from boththe FDAandEuropean Medicines Agencyfor use as a potential therapeutic option in patients with pancreatic cancer.

Preparations for a global, phase 3 registrational study evaluating mitazalimab in pancreatic cancer are underway, with plans to initiate the study in 2025.¹

“These results clearly represent a remarkable outcome in pancreatic cancer, with the robust DOR indicating highly consistent clinical benefit resulting in prolonged OS,” lead study investigator Jean-Luc van Laethem, MD, PhD, head of the Digestive Oncology Clinic in the Department of Gastroenterology at Erasmus Hospital University, in Belgium, Brussels, said in the news release. “Particularly noteworthy is the high proportion of patients surviving at the 18-month landmark, which most patients in this disease unfortunately do not see. With such a strong immunotherapeutic contribution, mitazalimab combined with mFOLFIRINOX has the potential to become the new treatment standard in pancreatic cancer, and we are eagerly awaiting the initiation of a randomized confirmatory study.”

References

1. Alligator Bioscience announces substantial overall survival benefit and unprecedented duration of response in the 18-month analysis from mitazalimab OPTIMIZE-1 phase 2 study in 1st line pancreatic cancer. News Release. Alligator Bioscience. June 26, 2024. Accessed June 26, 2024. https://alligatorbioscience.se/en/mfn_news/alligator-bioscience-announces-substantial-overall-survival-benefit-and-unprecedented-duration-of-response-in-the-18-month-analysis-from-mitazalimab-optimize-1-phase-2-study-in-1st-line-pancreatic-can/
2. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817-1825. doi:10.1056/NEJMoa1011923
3. Wainberg ZA, Melisi D, Macarulla T, et al. NALIRIFOX versus nab-paclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial. Lancet. 2023;402(10409):1272-1281. doi:10.1016/S0140-6736(23)01366-1
4. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Updated April 25, 2024. Accessed June 26, 2024. https://clinicaltrials.gov/ct2/show/NCT04888312
5. Alligator Bioscience’s phase 2 mitazalimab pancreatic cancer data published in The Lancet Oncology. Alligator Bioscience. June 3, 2024. Accessed June 26, 2024. https://alligatorbioscience.se/en/mfn_news/alligator-biosciences-phase-2-mitazalimab-pancreatic-cancer-data-published-in-the-lancet-oncology/
6. Alligator Bioscience announces positive interim results from mitazalimab OPTIMIZE-1 phase 2 trial in pancreatic cancer exceeding 50% objective response rate. Alligator Bioscience. News release. January 2, 2023. Accessed June 26, 2024. https://alligatorbioscience.se/en/mfn_news/alligator-bioscience-announces-positive-interim-results-from-mitazalimab-optimize-1-phase-2-trial-in-pancreatic-cancer-exceeding-50-objective-response-rate/