Immunotherapy combined with chemotherapy in the study increased median survival for metastatic pancreatic cancer to 14.3 months.

Compilation
The results of pancreatic cancer treatment are usually not very encouraging for the scientific community; the tumor microenvironment of these cancers makes it difficult for immunotherapy to work. The Optimize-1 Phase 1b/2 clinical trial is currently testing the combination of immunotherapy with chemotherapy in patients with advanced pancreatic ductal adenocarcinoma.

Results from the phase 1b/2 Optimize-1 clinical trial evaluating the safety and efficacy of combining a CD40 agonist with chemotherapy in patients with chemotherapy-naive or newly diagnosed pancreatic ductal adenocarcinoma show an objective response rate of 40% along with a median duration of response of 12.5 months and median overall survival of 14.3 months.

“These are really promising results, especially considering that we currently have no effective therapeutic strategies for these patients, so it is essential to continue exploring new options,” says Dr. Teresa Macarulla, a medical oncologist at Vall d’Hebron University Hospital and head of the Upper Gastrointestinal and Endocrine Tumours Group, who led the study.

Immunosuppressive tumor microenvironment

Over the past decades, immunotherapy has revolutionized the field of oncology. It is based on the activation of the patient’s immune system against tumor cells. However, immunotherapy is currently not effective in all patients and not for all types of tumors.

One of the major challenges to achieving therapeutic efficacy in pancreatic cancer is the presence of an immunosuppressive tumor microenvironment, which prevents adequate penetration of therapeutic molecules and immune cells. Therefore, it is necessary to continue to explore new immunotherapeutic strategies to activate the patient’s immune response against tumor cells.

What are CD40 agonist antibodies?

CD40 agonist antibodies are drugs that can stimulate different types of immune cells, such as B cells, monocytes or macrophages, against tumor cells, so that we move from an immunosuppressed tumor microenvironment to a microenvironment that can activate a potent immune response against the tumor.

“It’s like we’ve pressed the accelerator on the patient’s immune system. This antitumor activity, added to chemotherapy, is what we evaluated in the OPTIMIZE-1 trial,” says Dr. Makarulla.

Promising results

The Phase 1b/2 OPTIMIZE-1 study enrolled 77 patients with metastatic pancreatic ductal adenocarcinoma who had not previously received chemotherapy or were newly diagnosed. All patients received a combination of a CD40 IgG1 agonist antibody and chemotherapy. The objective response rate was 40%, meaning 40% of patients experienced tumor shrinkage, the median duration of response was 12.5 months, and the median progression-free survival was 7.7 months with a median overall survival of 14.3 months.

Phase 3 clinical trial to confirm the efficacy of the combination

“If we put these results in context and take into account that the median overall survival for de novo metastatic pancreatic ductal adenocarcinoma is less than one year, we can talk about promising results that open the door to studying this combination in a phase 3 clinical trial to confirm its efficacy in a larger number of patients.”

OPTIMIZE-1 Study Data Update at ESMO GI Congress

The results of this study were presented at the recent American Society for Medical Oncology (ASCO) Congress, held May 31 to June 4, and were published concurrently in The Lancet Oncology. Dr. Teresa Macarulla, the study’s senior investigator, is presenting updated data from the study today in a mini-oral presentation at the European Society for Medical Oncology Gastrointestinal Tumours Congress, ESMO GI, where she is also a scientific director.