MPO Could Represent Predictive OS Biomarker for CM24 Plus Nivolumab/Chemo in Second-Line PDAC

Additional data from a phase 2 trial (NCT04731467) showed that baseline serum myeloperoxidase (MPO) may represent a predictive biomarker for overall survival (OS) in patients with metastatic pancreatic ductal adenocarcinoma (PDAC) administered second-line treatment with the humanized monoclonal antibody CM24 in combination with nivolumab (Opdivo) and standard-of-care chemotherapy.¹

In this interim biomarker analysis of the phase 2 study, data showed that enhanced MPO levels were measured in more than 90% of enrolled patients, and the mean MPO was over 6-fold higher compared with healthy donors. The mean MPO was used as a threshold for evaluating MPO as a potential biomarker.

Patients with serum MPO levels below the mean MPO who were treated with CM24 plus nivolumab and chemotherapy experienced an OS improvement of 3.6 months vs those with an MPO level above the mean. The median OS in these two groups was 8.1 months and 4.5 months, respectively (HR 0.34; 95% CI, 0.099-1.149).

In a news release, Purple Biotech—the developer of CM24—noted that although these patient populations represent a small sample size, the findings suggest that serum MPO may be a predictive biomarker of OS for the treatment effect of CM24 plus nivolumab with standard chemotherapy.

“The concordant and consistent improvement in primary and all secondary end points including OS, progression-free survival [PFS], overall response rate [ORR], disease control rate [DCR] and CA19-9 [levels] are compelling, and the addition of a potential predictive biomarker provides further support for the potential of CM24 in combination with nivolumab plus the standard-of-care chemotherapy regimen [of] gemcitabine/nab-paclitaxel [Abraxane] or liposomal irinotecan [Onivyde; Nal-IRI]/5-fluorouracil, and leucovorin [Nal-IRI/5-FU/LV] to improve clinical outcomes for those with advanced metastatic PDAC,” Gil Efron, chief executive officer of Purple Biotech, stated in a news release. “We plan to report further clinical study data in the second half of 2024.”

CM24 inhibits CEACAM1, an immune checkpoint protein linked to tumor immune evasion and resistance to immune checkpoint inhibitors. CM24 was shown to bind to neutrophil extracellular traps (NETs) and suppress NET-induced cancer cell migration.

The phase 2 trial enrolled patients at least 18 years of age with locally advanced or metastatic PDAC following progression on 1 line of systemic therapy including fluoropyrimidine/irinotecan or gemcitabine/nab-paclitaxel. Key inclusion criteria consisted of 1 or more measurable lesions; an ECOG performance status of 0 or 1; and adequate organ function.²

Patients were randomly assigned 1:1 to receive CM24 plus nivolumab and chemotherapy or chemotherapy alone. Two chemotherapy regimens—Nal-IRI/5-FU/LV and gemcitabine/nab-paclitaxel—were used, and patients were assigned based on the prior chemotherapy regimen they received.

Patients in the experimental arms were administered CM24 at 20 mg/kg once every 2 weeks, nivolumab at 240mg/kg once every 2 weeks, and 1 of the 2 chemotherapy regimens: NI-IRI at 70 mg/m², 5FU at 2400mg/m², and LV at 200mg/m² once every 2 weeks; or gemcitabine at 1000 mg/m² and nab-paclitaxel at 125mg/m² administered once per week for 3 cycles. Remaining patients in control arms received 1 of the 2 chemotherapy regimens alone.

Initial interim results of the phase 2 study presented at the 2024 ASCO Annual Meeting demonstrated that the CM24 regimen was associated with a 26% reduction in risk of death (HR, 0.74; 95% CI, 0.31-1.77) and a 28% risk reduction in progression or death (HR, 0.72; 95% CI, 0.33-1.60).

The median OS was 7.72 months (95% CI, 4.00-8.11) in the combination arm vs 5.62 months (95% CI, 3.22-7.89) in the chemotherapy arm. The median PFS for the experimental group was 3.8 months (95% CI, 1.8-5.0) vs 1.9 months (95% CI, 0.9-3.6) for the control arm.

In addition to the prolongation of both OS and PFS with CM24, the ORR was also higher in the experimental group at 25% vs 7%. The respective DCRs were 62.5% and 40%.

Regarding safety, grade 3 or higher treatment-emergent adverse effects (TEAEs) occurred in 94% of patients receiving the CM24 combination and 67% of patients receiving chemotherapy alone.

Further details from the biomarker data will be presented at an upcoming medical conference.¹

References

1. Purple Biotech reports additional positive interim results from its randomized phase 2 pancreatic cancer study with CM24 regarding a potential predictive biomarker for overall survival benefit. News release. June 27, 2024. Accessed June 27, 2024. https://www.globenewswire.com/news-release/2024/06/27/2905110/0/en/Purple-Biotech-Reports-Additional-Positive-Interim-Results-from-its-Randomized-Phase-2-Pancreatic-Cancer-Study-with-CM24-Regarding-a-Potential-Predictive-Biomarker-for-Overall-Surv.html
2. Macarulla T, Cecchini M, Garcia-Carbonero R, et al. Interim results of the randomized phase 2 cohort of study FW-2020-01 assessing the efficacy, safety and pharmacodynamics of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer. J Clin Oncol. 2024;42(17):LBA4143. doi:10.1200/JCO.2024.42.17_suppl.LBA4143