- Recently presented at the 2024 ASCO Annual Meeting and published in parallel in The Lancet Oncology, results of the OPTIMIZE-1 multicenter phase 1b/2 study demonstrate the promise of the CD40 agonistic IgG1 antibody, mitazalimab, in combination with FOLFIRINOX chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer.
- Led by Jean-Luc Van Laethem at the Erasmus Hospital, Hôpital Universitaire de Bruxelles in Belgium, this study met its primary endpoint with an objective response rate of 40%, demonstrated a manageable safety profile and an encouraging median duration of response of 12.5%. These findings warrant continued development of this combination in a larger phase 3, randomized, controlled trial.
- Updated data of this single-arm study were presented today during a mini oral session at the ESMO Gastrointestinal Cancers Annual Congress 2024, by senior author Teresa Macarulla, Medical Oncologist at the Vall d’Hebron University Hospital and Head of the Vall d’Hebron Institute of Oncology’s (VHIO) Upper Gastrointestinal and Endocrine Tumors Group.
The OPTIMIZE-1 single-arm, multicenter phase Ib/2 clinical trial explored the safety and antitumor activity of mitazalimab, a human CD40 agonistic IgG1 antibody, combined with FOLFIRINOX chemotherapy in patients with previously untreated metastatic pancreatic ductal adenocarcinoma (PDAC).
“Pancreatic ductal adenocarcinoma is the most common type of pancreatic cancer and carries a very poor prognosis. Despite significant advances in systemic therapy, median overall survival in de novo metastatic disease is still less than one year. Developing more effective treatment strategies to combat this highly complex and aggressive malignancy represents an urgent, unmet clinical need,” says Teresa Macarulla, a Medical Oncologist at the Vall d’Hebron University Hospital (HUVH), Head of VHIO’s Upper Gastrointestinal and Endocrine Tumors Group, and senior author of this study.
Immunosuppressive tumor microenvironment
The cancer immunotherapy revolution has accelerated the approval of an expanding array of immune-based therapies, consisting of immune checkpoint blockade and immuno-oncology (IO) combinations, for the treatment of a diverse range of solid tumours. However, only a fraction of patients respond to these potent new anti-cancer weapons.
“PDAC is characterized by a complex and immunosuppressive microenvironment, preventing the sufficient penetration of therapeutic agents into tumor tissue as well as immune cells. Novel strategies aimed at unlocking the anticancer promise of agonist antibodies could help to overcome this challenging milieu by activating the immune response to eradicate cancer,” explains Macarulla.
Agonistic anti-CD40 antibodies can stimulate different types of immune cells including B cells, monocytes or macrophages to trigger anti-tumor immune responses and counteract immunosuppression in the tumor microenvironment. The investigators evaluated mitazalimab, a potent CD40 agonist, in combination with FOLIFIRINOX chemotherapy in 77 chemotherapy-naive and newly diagnosed patients with metastatic pancreatic ductal adenocarcinoma (PDAC) across 14 university hospitals in Belgium, France, and Spain, including the Vall d’Hebron University Hospital (HUVH) in Barcelona.
Recently presented at the 2024 ASCO Annual Meeting and published in parallel in The Lancet Oncology (1), results of the primary analysis show an objective response rate of 40%, a median duration of response, overall survival and progression-free survival of 12.5, 14.3 and 7.7 months, respectively, and a manageable safety profile. These encouraging data support further exploration of this novel combination in this setting.
“These promising results warrant a larger randomized study to confirm the efficacy of this combined treatment strategy for this particularly complex and aggressive tumor type with very low survival rates and limited treatment options,” concludes Teresa Macarulla.
Updated results of this single-arm study were presented today during a mini oral session at the ESMO Gastrointestinal Cancers Annual Congress 2024 (2) by Teresa Macarulla, a Scientific Co-Chair of this meeting.
###
References
- Van Laethem JL, Borbath I, Prenen H, Geboes KP, Lambert A, Mitry E, Cassier PA, Blanc JF, Pilla L, Batlle JF, Garrote MR, Pazo-Cid RA, Gallego I, Smith KE, Ellmark P, Pico de Coaña Y, Ambarkhane SV, Macarulla T. 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 May 31:S1470-2045(24)00263-8. doi: 10.1016/S1470-2045(24)00263-8. Epub ahead of print. PMID: 38834087.
- ESMO Gastrointestinal Cancers Annual Congress 2024, 26 – 29 June, Munich, Germany
Session Details
Mini Oral session 3
Date: Saturday, 29 June
Session Time: 08:45h – 10:00h
Chairs: Eric Van Cutsem (Leuven, Belgium), Magali Svrcek (Paris, France), Zev A. Wainberg (Los Angeles, USA)
Abstract: 280MO – CD40 agonist mitazalimab combined with mFOLFIRINOX (mFFX) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): Primary analysis of the OPTIMIZE-1 phase Ib/II study
Lecture Time: 09:00h – 09:05h
Speaker: Teresa Macarulla (Barcelona, Spain)
