Purple Biotech hopes its lead asset against metastatic pancreatic cancer will one day show its true colors as a potential first-in-class drug in a larger study—but, for now, it has preliminary, midstage trial results demonstrating measurable gains in overall survival.
Presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, the late-breaking poster data from the company’s phase 2b trial also illustrated improvements in progression-free survival as well as in a diagnostic biomarker linked to pancreatic ductal adenocarcinoma.
Purple’s anti-CEACAM1 antibody, dubbed CM24, was offered to previously treated patients in combination with Bristol Myers Squibb’s Opdivo (nivolumab), alongside the physician’s choice between one of two standard-of-care chemotherapy regimens—either gemcitabine and nab-paclitaxel, or liposomal irinotecan plus 5-fluorouracil and leucovorin. Those patients were then compared to those who received either chemotherapy regimen alone.
According to the company, the randomized, open-label study was not powered for hypothesis testing. While the interim findings delivered at ASCO consider 31 patients split between the two arms—with a data cutoff of May 8—the trial as a whole enrolled 63 participants across the U.S., Spain and Israel. Broader top-line results are expected in the latter half of this year. The study is also open to patients with other solid tumors, including colorectal cancer, non-small cell lung cancer, ovarian cancer and melanoma.
The addition of CM24 and Opdivo was able to extend median overall survival in pancreatic cancer by 2.1 months and median progression-free survival by 1.9 months. According to the company, this also resulted in about a 26% reduction in the risk of death.
Purple believes that by blocking the checkpoint protein CEACAM1 on white blood cells with CM24, tumor cells will have a harder time evading the body’s immune responses as well as developing resistance to other checkpoint inhibitors such as Opdivo, which has struggled to succeed as a monotherapy in other studies against advanced pancreatic cancer, a notoriously recalcitrant disease.
“These patients face very limited time with their families, and the prospect of potentially lengthening their lives while delaying their disease progression by approximately two months overall is clinically meaningful,” principal investigator Michael Cecchini, M.D., an assistant professor of medicine at Yale Cancer Center, said in a statement. “These data justify further investigation of CM24 in combination with nivolumab together with standard-of-care chemotherapy to potentially improve outcomes for patients facing a very poor prognosis from this type of tumor.”
The initial data captured a total median OS of 7.72 months compared to 5.62 months in the control arm, as well as median PFS times of 3.8 months and 1.9 months, respectively. In addition, overall response rates were logged as 25% versus 7%—with four partial responses, plus one in the control arm—while disease control rates reached 63% compared to 40%.
The study also noted patients’ levels of CA19-9, a common clinical serum biomarker used to help predict pancreatic tumor stages and responses to therapy, radiation and surgery. Purple said there was “a consistent and continuous decrease of CA19-9” over a span of 16 weeks, amounting to 61% on average among the second-line patients that received CM24 and Opdivo, compared to an increase of 34% within the control arm.
In terms of safety, 15 out of the 16 patients in the experimental arm reported serious side effects, listed as grade 3 and above, compared to 10 out of 15 in the control arm. The most common included diarrhea and fatigue, and the company described the adverse events as manageable. Both sides of the study recorded patients’ median time from their initial diagnoses as 18 months.
“We are highly encouraged by the meaningful results of our primary endpoint, overall survival, as well as by the concordant and consistent improvement in all secondary endpoints including PFS, ORR, DCR and CA19-9,” said Gil Efron, CEO of Purple, which picked up CM24 through the 2020 acquisition of FameWave when the company was known as Kitov Pharma.