Pancreatic cancer is one of the most difficult to treat cancers, and KRAS has – until recently – been thought to be ‘undruggable.’

The data presented here for sotorasib carry huge potential as a future targeted treatment option for patients with refractory KRASG12C pancreatic cancer and will hopefully open the doors for the development of other novel RAS inhibitors for this and other cancers.” – Kimmie Ng, MD, MPH, ASCO Expert in Pancreatic Cancer

Pancreatic cancer is a leading cause of cancer-related deaths1; however, despite decades of research, limited progress has been made to improve survival.

There are currently no FDA-approved treatment options for patients with pancreatic cancer that has progressed on first- and second-line chemotherapy.

Sotorasib is active and well tolerated in patients with metastatic pancreatic cancer with a KRASG12C mutation, according to research being presented in the February 15, 2022, ASCO Plenary Series session.

Sotorasib is an irreversible KRASG12C inhibitor, which blocks certain enzymes that cancer cells need to grow and may kill cancer cells. It has already shown efficacy in and is FDA-approved for the treatment of lung cancers with a KRASG12C mutation.

Approximately 1-2% of metastatic pancreatic cancers have a KRASG12C mutation. Treatment options are limited for this type of pancreatic cancer. In most cases, patients are treated with cytotoxic chemotherapy combinations.

After progression on two lines of chemotherapy, however, there are no therapies that improve survival. According to the researchers, expected survival for a patient newly diagnosed with metastatic pancreatic cancer is 6-12 months. Once the cancer has progressed after first- and second-line chemotherapy, survival is usually less than 6 months.

CodeBreaK100 is an international, single arm, phase I/II study evaluating the efficacy and safety of sotorasib in patients with advanced solid tumors with a KRASG12C mutation.

The trial included patients who had received at least one prior systemic therapy and patients who were not eligible or not able to tolerate available therapies. The primary efficacy endpoint was confirmed objective response rate (ORR), and secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

A total of 38 patients with stage IV pancreatic cancer received sotorasib once daily. Most patients (79%) had two or more prior lines of therapy. Median treatment duration was 4.1 months with a median follow-up of 16.8 months. Eight patients (21.1%) had a confirmed partial response to treatment. The percentage of patients in which the cancer improved or remained stable was 84.2%, median PFS was 3.98 months, and median OS was 6.87 months.

Sotorasib was well-tolerated with no treatment-related adverse events that were fatal or that resulted in discontinuation.

“These data are promising for pancreatic cancer patients with high unmet medical need who have limited treatment options,” said lead author John H. Strickler, MD, medical oncologist at Duke University Medical Center.

Source: ASCO