BL-8040 plus Keytruda and Chemotherapy in Metastatic Pancreatic Cancer: COMBAT Trial

At the ESMO Immuno-Oncology Congress 2019, Dr. Manuel Hidalgo presented findings from the COMBAT Phase 2a clinical trial. The study investigated a novel combination of the CXCR4 inhibitor BL-8040 (Motixafortide), the anti-PD-1 therapy Keytruda (Pembrolizumab), and standard chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had progressed on gemcitabine-based first-line therapy.

Study Design: COMBAT Trial

This multicenter trial enrolled 22 patients. The treatment regimen consisted of a 5-day lead-in with BL-8040 monotherapy, followed by combination therapy with:

• BL-8040: Twice weekly.
• Keytruda: Every three weeks.
• Chemotherapy: Onivide (liposomal irinotecan), 5-FU, and leucovorin every two weeks.

The primary endpoint was the objective response rate (ORR).

Key Results

Among the 15 evaluable patients at the time of analysis:

• Objective Response: 4 patients (27%) achieved a partial response (PR).
• Disease Control: 8 patients (53%) had stable disease (SD).
• Biomarker Response: Patients with responses showed an initial transient increase in the tumor marker CA19-9 followed by a significant decline, coinciding with tumor shrinkage.
• Survival: Median progression-free survival (PFS) and overall survival (OS) data were still maturing but showed encouraging early signals.

Safety Profile

Serious adverse events were reported in 10 patients (15 events total). Two patients discontinued treatment due to adverse reactions. Overall, the combination was considered to have a manageable safety profile.

Conclusion

Dr. Manuel Hidalgo concluded that the combination of BL-8040, Keytruda, and chemotherapy demonstrates promising antitumor activity and a high disease control rate in patients with heavily pretreated metastatic pancreatic cancer. This strategy aims to modulate the tumor microenvironment to enhance the effectiveness of immunotherapy in this challenging disease.

Source: ESMO Immuno-Oncology Congress 2019 - COMBAT Trial Highlights

#PancreaticCancer #BL8040 #Motixafortide #Keytruda #Pembrolizumab #COMBATTrial #Immunotherapy #CancerResearch

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