Mitazalimab/Chemo Prolongs Survival, Responses in Pancreatic Cancer

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More than half of the patients who received mitazalimab plus chemotherapy experienced an unconfirmed objective response in the phase 2 OPTIMIZE-1 study.

"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," according to Jean-Luc van Laethem, MD.

"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," according to Jean-Luc van Laethem, MD.

Mitazalimab in combination with modified leucovorin calcium/folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) produced an overall survival (OS) benefit and elicited responses among patients with metastatic pancreatic cancer, according to a press release on 18-month follow-up data from the phase 2 OPTIMIZE-1 trial (NCT04888312).1

At 18 months, the OS rate with the mitazalimab-based combination was 36.2% compared with a historical rate of 18.6% in patients who received FOLFIRINOX alone.2 Additionally, the median OS was 14.9 months with study treatment vs 11.1 months with FOLFIRINOX alone.

The updated confirmed objective response rate (ORR) was 42.1% with mitazalimab/chemotherapy vs 31.6% in a historical population treated with FOLFIRINOX alone. Among 57 evaluable patients, the unconfirmed ORR was 54.4% following study treatment. Data also showed a median duration of response (DOR) of 12.6 months with the mitazalimab combination compared with 5.9 months with FOLFIRINOX.

Mitazalimab-based treatment also yielded a median progression-free survival (PFS) of 7.7 months. The 12-month PFS rate was 35.1% with this regimen vs 12.1% with FOLFIRINOX.

“These results represent a remarkable outcome in pancreatic cancer, with the robust [DOR] indicating highly consistent clinical benefit resulting in prolonged [OS],” lead trial investigator Jean-Luc van Laethem, MD, professor and head of the Digestive Oncology Clinic in the Gastroenterology Department of Erasmus Hospital (ULB) Brussels, said in the press release.1

“Particularly noteworthy is the high proportion of patients surviving at the 18-month landmark, which most patients in this disease unfortunately do not [have]. 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,” he added.

In the open-label OPTIMIZE-1 trial, patients received the investigational monoclonal antibody mitazalimab intravenously every 2 weeks in combination with mFOLFIRINOX.3

The trial’s primary end points were dose-limiting toxicities in part 1 and ORR in part 2. Secondary end points included adverse effects, immunogenicity, pharmacokinetics, DOR, disease control rate, PFS, and OS.

Patients 18 years and older with previously untreated metastatic pancreatic ductal adenocarcinoma and an ECOG performance status of 0 or 1 were eligible for enrollment on the trial. Additional requirements for study entry included having measurable disease based on RECIST v1.1 criteria, no prior chemotherapy, no prior abdominal radiation, a life expectancy of at least 3 months, and adequate hematologic laboratory values.

Those with known central nervous system (CNS) metastases or carcinomatous meningitis or prior chronic diarrhea, inflammatory disease in colon or rectum, or resolved intestinal obstruction were ineligible for study entry. Patients were also unable to enroll if they had uncontrolled intercurrent illness, known Gilbert’s disease, known fructose intolerance, or complete dihydropyrimidine dehydrogenase deficiency.

Investigators will present data from the OPTIMIZE-1 trial at the European Society for Medical Oncology (ESMO) Gastrointestinal Cancers Congress 2024.

“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 first-line pancreatic cancer….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,” Søren Bregenholt, chief executive officer at Alligator Bioscience, the developers of mitazalimab, concluded.1

The FDA granted orphan drug designation to mitazalimab as a treatment for those with pancreatic cancer in May 2023.4

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://tinyurl.com/bdhwjxjd
  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. Safety and efficacy of mitazalimab in combination with chemotherapy in pancreatic cancer patients (OPTIMIZE-1). ClinicalTrials.gov. Accessed June 26, 2024. https://tinyurl.com/2p8warah
  4. Alligator Bioscience receives FDA orphan drug designation for mitazalimab in pancreatic cancer. News release. Alligator Bioscience. May 18, 2023. Accessed June 26, 2024. bit.ly/43qcPb7
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