ASCO: Early Purple data strengthens in metastatic pancreatic cancer

Purple Biotech is hopeful that CM24, its lead candidate for treating metastatic pancreatic cancer, might show promise as a first-in-class drug in future larger studies. In the meantime, preliminary phase 2b trial results presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago demonstrate measurable gains in overall survival.

The late-breaking poster data from the phase 2b trial also indicated improvements in progression-free survival and a diagnostic biomarker associated with pancreatic ductal adenocarcinoma. CM24, an anti-CEACAM1 antibody, was administered to previously treated patients along with Bristol Myers Squibb’s Opdivo (nivolumab). Patients also received a choice of standard chemotherapy regimens: either gemcitabine and nab-paclitaxel or liposomal irinotecan plus 5-fluorouracil and leucovorin. These patients were compared to those who received only the chemotherapy regimens.

The open-label, randomized study was not powered for hypothesis testing. Interim results presented at ASCO involved 31 patients divided into two groups, with data cut off on May 8. The full trial enrolled 63 participants across the U.S., Spain, and Israel. Broader top-line results are anticipated later this year. The study is also open to patients with other solid tumors, such as colorectal cancer, non-small cell lung cancer, ovarian cancer, and melanoma.

The combination of CM24 and Opdivo was found to extend median overall survival in pancreatic cancer by 2.1 months and median progression-free survival by 1.9 months. According to Purple Biotech, this equated to a 26% reduction in the risk of death. The company believes that by blocking the checkpoint protein CEACAM1 on white blood cells with CM24, it becomes more difficult for tumor cells to evade the immune response and develop resistance to other checkpoint inhibitors like Opdivo. Opdivo has not been very successful as a monotherapy against advanced pancreatic cancer, a very challenging disease.

“These patients have limited time with their families, and the potential to extend their lives while delaying disease progression by approximately two months overall is clinically significant,” said Michael Cecchini, M.D., principal investigator and assistant professor of medicine at Yale Cancer Center. “These data support further study of CM24 in combination with nivolumab and standard chemotherapy to improve outcomes for patients facing a poor prognosis from this type of tumor.”

The initial data showed a total median overall survival (OS) of 7.72 months compared to 5.62 months in the control group. Median progression-free survival (PFS) times were 3.8 months compared to 1.9 months, respectively. The overall response rates were 25% compared to 7%, with four partial responses in the experimental group and one in the control group. Disease control rates were 63% compared to 40%.

The study also evaluated patients' levels of CA19-9, a clinical serum biomarker used to predict pancreatic tumor stages and responses to therapy, radiation, and surgery. There was a consistent decrease of CA19-9 over 16 weeks, averaging 61% in the CM24 and Opdivo group, compared to a 34% increase in the control group.

In terms of safety, 15 out of 16 patients in the experimental group experienced serious side effects (grade 3 and above), compared to 10 out of 15 in the control group. Common side effects included diarrhea and fatigue, which the company described as manageable. Both groups had a median time from initial diagnosis of 18 months.

“We are encouraged by the meaningful results of our primary endpoint, overall survival, as well as the consistent improvement in all secondary endpoints, including PFS, ORR, DCR, and CA19-9,” said Gil Efron, CEO of Purple Biotech. The company acquired CM24 in 2020 through the acquisition of FameWave when it was known as Kitov Pharma.