CM24 Plus Nivolumab Shows Promise in Metastatic Pancreatic Cancer
核心洞察
A phase 2 study reveals that CM24 combined with nivolumab and chemotherapy improves efficacy endpoints in second-line metastatic pancreatic ductal adenocarcinoma (搜索) (PDAC (搜索)).
The combination therapy showed an increase in median overall survival (OS) to 7.92 months compared to 5.55 months with chemotherapy alone.
Patients with specific pretreatment serum CEACAM1 (搜索) levels demonstrated statistically significant improvements in OS and PFS with the CM24 combination.
A phase 2 study has revealed that the novel monoclonal antibody CM24, when combined with nivolumab (Opdivo) and standard-of-care chemotherapy, demonstrates improved efficacy compared to chemotherapy alone in the second-line treatment of metastatic pancreatic ductal adenocarcinoma (搜索) (PDAC (搜索)). The study (NCT04731467) assessed key efficacy endpoints, showing promising results for patients with this challenging cancer.
The intention-to-treat analysis indicated that the median overall survival (OS) in the CM24 combination arm (n = 16) was 7.92 months, compared to 5.55 months in the standard chemotherapy arm (n = 15), with a hazard ratio of 0.81 (95% CI, 0.38-1.71). The median progression-free survival (PFS) also improved, reaching 3.9 months in the combination arm versus 2.0 months in the chemotherapy arm (HR, 0.75; 95% CI, 0.35-1.61). Additionally, the overall response rates (ORRs) were 25% in the CM24 arm compared to 7% in the chemotherapy arm, while disease control rates (DCRs) were 63% and 47%, respectively.
Mechanism of Action
CM24 is a first-in-class multi-functional antibody that blocks CEACAM1 (搜索), a membrane glycoprotein highly expressed on neutrophil extracellular traps (NETs). CEACAM1 promotes tumor invasiveness, metastasis, and immune evasion by acting as a pro-angiogenic and anti-apoptotic agent.
Biomarker Analysis
Subgroup analysis of patients with pretreatment serum CEACAM1 (搜索) levels between 6,000 pg/mL and 15,000 pg/mL showed a statistically significant improvement with the combination therapy. The median OS was 9 months in the CM24 arm (n = 4) versus 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 analysis in patients with similar CEACAM1 (搜索) levels and pretreatment serum myeloperoxidase levels between 200 ng/mL and 600 ng/mL revealed a median OS of 7.90 months in the CM24 arm (n = 13) compared to 5.50 months in the chemotherapy arm (n = 11; HR, 0.39; 95% CI, 0.16-0.98). The median PFS was 4.1 months versus 1.9 months (HR, 0.28; 95% CI, 0.11-0.73), respectively, and the ORRs were 31% versus 0%, with DCRs at 69% versus 36%.
Safety and Tolerability
The combination therapy was generally well-tolerated. The most frequent grade 3 or higher treatment-emergent adverse effects included diarrhea (investigational arm, n= 4; control arm, n =1), fatigue (n = 2; n = 0), and neutropenia (n = 2; n =0).
Future Directions
Purple Biotech (搜索) is planning a 3-arm phase 2b clinical study in selected indications, potentially targeting patients based on identified biomarkers. According to Michael Cecchini, MD, associate professor of medicine at Yale Cancer Center, these findings support further investigation of CM24 in combination with a checkpoint inhibitor and SOC chemotherapy to improve outcomes not only in PDAC (搜索) but also in other challenging cancer types.