Purple Biotech (PPBT) has announced positive final results from a mid-stage study of its lead candidate, CM24, in combination with Bristol Myers Squibb’s (BMY) Opdivo (nivolumab) and standard-of-care (SoC) chemotherapy for treating patients with pancreatic ductal adenocarcinoma (PDAC). The study demonstrated a statistically significant improvement in overall survival (OS) and other key efficacy endpoints.
The Phase II study evaluated CM24, a humanized monoclonal antibody that blocks CEACAM1, in combination with Opdivo and either gemcitabine/nab-paclitaxel or liposomal irinotecan (Nal-IRI)/5-fluorouracil (5-FU) and leucovorin (LV) (Nal-IRI/5FU/LV) chemotherapies in second-line metastatic PDAC patients. The primary endpoint was OS, with secondary endpoints including progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR).
Improved Outcomes with CM24 Combination Therapy
Data from the Nal-IRI/5FU/LV portion of the study showed that patients treated with the CM24 combination therapy achieved a median OS of 7.92 months compared to 5.55 months for the chemotherapy arm. The 6-month OS rates were 53% and 47%, respectively. The median PFS was also longer at 3.9 months versus 2 months, with improved three and six-month PFS rates in the combination group. The ORR in the CM24+Opdivo+Nal-IRI/5FU/LV arm was 25%, significantly higher than the 7% observed in the Nal-IRI/5FU/LV arm. The DCR of 63% in the combo arm surpassed the 47% in the monotherapy arm.
Biomarker Analysis Highlights Potential Subgroup Benefit
Further analysis based on pretreatment serum CEACAM1 levels revealed significantly better outcomes in the treatment arm compared with the control. The treatment arm showed a 79% reduction in the risk of death, with a median OS improvement of 5.1 months. There was also a greater than 90% reduction in the risk of progression or death, with a median PFS improvement of 2.9 months. The ORR was notably higher in the treatment arm, achieving 50% compared with 0% in the control. Similar efficacy benefits were observed in patients with pretreatment serum MPO levels of 200 ng/mL and 600 ng/mL.
Future Directions
The investigational combination therapy was generally well-tolerated with an acceptable safety profile. Purple Biotech plans to initiate a three-arm phase IIb study comparing either CM24 plus a PD1 inhibitor or CM24 monotherapy to SoC in multiple tumor types selected based on their NET and CEACAM1 expressions. The study is expected to enroll patients with higher serum levels of CEACAM1 and MPO, as they are potentially more likely to benefit from CM24 treatment.
