Mitazalimab Combo Yields Meaningful Survival Benefit in Metastatic PDAC

Immunological profile changes occurring in between the priming dose of mitazalimab and the initial dose of mFOLFIRINOX were associated with improvements in efficacy outcomes.

Combining mitazalimab with modified leucovorin calcium/folinic acid, fluorouracil, irinotecan, and oxaliplatin (mFOLFIRINOX) elicited responses and survival benefits among patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to updated efficacy and biomarker data from the phase 2 OPTIMIZE-1 trial (NCT04888312) presented at the 2024 Society for Immunotherapy of Cancer Annual Meeting (SITC).¹

Among 57 patients who received mitazalimab at the 900-µg/kg dose, study treatment produced a confirmed overall response rate (ORR) of 42.1%, which included 23 partial responses (PRs) and 1 complete response (CR). When accounting for unconfirmed responses, the ORR in this cohort was 54.4%. Additionally, the median duration of response (DOR) was 12.6 months.

The mitazalimab-based regimen yielded a median overall survival (OS) of 14.9 months. Data also showed an 18-month OS rate of 36.2%, which exceeded an 18-month rate of 18.6% in a historical cohort of patients with metastatic pancreatic cancer who received FOLFIRINOX alone.² The median progression-free survival (PFS) with the mitazalimab combination was 7.7 months. At the time of analysis, 19 patients (33%) remained in the study, and 9 continued to receive therapy.

Immunological profile changes occurring in between the priming dose of mitazalimab and the initial dose of mFOLFIRINOX were associated with improvements in efficacy outcomes. According to the investigators, these findings may inform the design of a future confirmatory trial assessing mitazalimab plus mFOLFIRINOX in patients with metastatic PDAC.

“The OPTIMIZE-1 phase 2 data, in particular, are very exciting as these show mitazalimab increases the chance of being alive after 18 months by 95% compared [with] the current standard-of-care chemotherapy, FOLFIRINOX,” Sumeet Ambarkhane, MD, chief medical officer at Alligator Bioscience, the developers of mitazalimab, stated in a press release on these findings.¹ “This clinically meaningful survival benefit shows the potential of mitazalimab to make a significant difference for [patients with] pancreatic cancer, who still sadly have very poor prognosis.”

In the phase 1b portion of the OPTIMIZE-1 trial, patients received mitazalimab at 450 μg/kg or 900 μg/kg intravenously plus oxaliplatin at 85 mg/m², leucovorin at 400 mg/m², irinotecan at 150 mg/m², and fluorouracil at 2400 mg/m2.³

The trial’s primary end points were the recommended phase 2 dose in the phase 1b portion and ORR per RECIST v1.1 guidelines in the phase 2 portion. Secondary end points included best overall response, DOR, disease control rate, time to next cancer therapy, PFS, OS, and safety.

Patients 18 years and older with histologically confirmed metastatic PDAC, no prior chemotherapy, an ECOG performance status of 0 or 1, and measurable disease based on RECIST v1.1 guidelines were eligible for enrollment on the trial. Patients who had non-ductal pancreatic tumors were ineligible to enroll.

Investigators previously published findings from the OPTIMIZE-1 trial in The Lancet Oncology.3 Safety data showed that grade 3 or higher treatment-emergent adverse effects affected 79% (n = 55/70) of patients, with the most common toxicities including neutropenia (26%), hypokalemia (16%), anemia (11%), and thrombocytopenia (11%). Investigators reported 28 deaths due to disease progression; no deaths were related to study treatment.

“The long-lasting responses and biomarker associations reported in OPTIMIZE-1 are highly encouraging, implying a potential immunomodulatory contribution of mitazalimab. Data are supportive of the continued development of mitazalimab and mFOLFIRINOX in metastatic [PDAC] in a confirmatory setting,” lead study author Jean-Luc Van Laethem, MD, professor at the Laboratory of Experimental Gastroenterology at the Université Libre de Bruxelles in Brussels, Belgium, and coauthors wrote in the publication.³

References

1. Alligator Bioscience presents an update with clinical and biomarker results with mitazalimab in phase 2 pancreatic cancer at SITC 2024. News release. Alligator Bioscience. November 6, 2024. Accessed November 7, 2024. https://tinyurl.com/5n86mhps
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. Van Laethem JL, Borbath I, Prenen H, et al. Combining CD40 agonist mitazalimab with mFOLFIRINOX in previously untreated metastatic pancreatic ductal adenocarcinoma (OPTIMIZE-1): a single-arm, multicentre, phase 1b/2 study. Lancet Oncol. 2024;25(7):853-864. doi:10.1016/S1470-2045(24)00263-8