CM24 Plus Nivolumab and Chemo Displays Efficacy vs Chemo Alone in Metastatic PDAC

Pancreatic cancer / Image credit:

magicmine — stock.adobe.com

The novel, humanized monoclonal antibody CM24 plus nivolumab (Opdivo) and standard-of-care (SOC) chemotherapy improved all efficacy end points vs SOC chemotherapy alone in the second-line treatment of patients with metastatic pancreatic ductal adenocarcinoma (PDAC), according to findings from a phase 2 study (NCT04731467).

Results from the intention-to-treat population of the study showed that the median overall survival (OS) in the CM24 combination arm (n = 16) was 7.92 months compared with 5.55 months in the SOC chemotherapy arm (n = 15; HR, 0.81; 95% CI, 0.38-1.71). The median progression-free survival (PFS) was 3.9 months vs 2.0 months, respectively (HR, 0.75; 95% CI, 0.35-1.61), and the overall response rates (ORRs) and disease control rates (DCRs) were 25% vs 7% and 63% vs 47%, respectively.

The first-in-class multi-functional antibody blocks CEACAM1, a multi-faceted membrane glycoprotein that is one of the main proteins present on neutrophil extracellular traps (NETs), also acting as a pro-angiogenic and anti-apoptotic agent collectively promoting tumor invasiveness, metastasis, and immune evasion, according to Purple Biotech.

“We are very excited about the final data, demonstrating CM24’s clear and consistent improvement across all efficacy end points evaluated in our randomized phase 2 study,” Gil Efron, chief executive officer of Purple Biotech, said in a news release. “The enhanced results in patients with CEACAM1 and other serum markers gives us further optimism that a biomarker enriched patient population selection could further strengthen CM24’s magnitude of efficacy, potentially positioning CM24 as a treatment for multiple CEACAM1-expressing malignancies in line with its mechanism of action.”

Key Enrollment Information

A total of 63 eligible patients with PDAC were enrolled in the phase 2 trial across 18 centers in the US, Spain, and Israel. There were 2 parallel and independent randomized study cohorts with a total of 2 arms per cohort. Patients in the experimental arms received CM24 plus nivolumab and a choice of 1 of 2 SOC chemotherapies in the second-line setting, dependent on the first-line therapy regimen received. Chemotherapies included gemcitabine/nab-paclitaxel or liposomal irinotecan (Onivyde)/5-fluorouracil (5-FU) and leucovorin. The control arms included either respective chemotherapy alone. Of the 63 patients, 32 were enrolled in the gemcitabine/nab-paclitaxel arms and 31 were enrolled in the liposomal irinotecan/5-FU/leucovorin arms.

Furthermore, the gemcitabine/nab-paclitaxel-based part of the study was affected by informative censoring of the control arm that led to an imbalance between the control and experimental arms, rendering this part of the study unsuitable for analysis, according to findings from the news release. However, it was noted that this part of the study had no impact on the CM24 plus nivolumab and liposomal irinotecan/5-FU/leucovorin portion of the trial.

Additionally, OS served as the primary end point of the study and the secondary end points included PFS, ORR and DCR. CA19-9 and further exploratory biomarkers were also evaluated.

Additional Findings From the Study

Regarding safety, the investigative combination was well tolerated. The most frequent grade 3 or higher treatment-emergent adverse effect consisted of diarrhea (investigational arm, n= 4; control arm, n =1), fatigue (n = 2; n = 0) and neutropenia (n = 2; n =0).

A subgroup analysis of patients with a range of pretreatment serum CEACAM1 levels between 6,000 pg/mL and 15,000 pg/mL showed that treatment with the combination yielded statistically significant results vs chemotherapy alone. The median OS was 9 months in the investigative arm (n = 4) vs 3.9 months in the chemotherapy arm (n = 7; HR, 0.21; 95% CI, 0.04-1.06). The median PFS was 4.7 months compared with 1.8 months, respectively (HR, < 0.1; 95% CI, 0-inf).

Further, among patients with the same pretreatment serum CEACAM1 levels and pretreatment serum myeloperoxidase levels of 200 ng/mL and 600 ng/mL, the median OS was 7.90 months in the investigative arm (n = 13) vs 5.50 months in the chemotherapy arm (n = 11; HR, 0.39; 95% CI, 0.16-0.98), which was also statistically significant. The median PFS observed was 4.1 months vs 1.9 months (HR, 0.28; 95% CI, 0.11-0.73), respectively, and the ORRs were 31% vs 0%. The DCRs were 69% vs 36%, respectively.

Purple Biotech added that a 3-arm phase 2b clinical study is planned in multiple selected indications, which will potentially target patients based on biomarkers.

“The promising results in [patients with] PDAC, along with the identification of a potential patient subgroup that may benefit from targeting CEACAM1 and NET serum levels, potentially position CM24 as an encouraging treatment option,” Michael Cecchini, MD, associate professor of medicine at Yale Cancer Center in New Haven, Connecticut, and a principal investigator of the study, commented. “As a clinician, it is inspiring to see data that suggest the potential for improved outcomes in patients with late-stage metastatic PDAC, who desperately need new and effective therapies. These findings support further investigation of CM24 in combination with a checkpoint inhibitor and SOC chemotherapy to improve outcomes not only in PDAC but also in other challenging cancer types.”

Reference

Purple Biotech reports positive final results from randomized phase 2 study of CM24 in second line pancreatic cancer. News Release. Purple Biotech. December 2, 2024. Accessed December 2, 2024. https://www.globenewswire.com/news-release/2024/12/02/2989659/0/en/Purple-Biotech-Reports-Positive-Final-Results-from-Randomized-Phase-2-Study-of-CM24-in-Second-Line-Pancreatic-Cancer.html