Advertisement

ESMO Immuno-Oncology 2019: CXCR4 Inhibitor in Combination With Pembrolizumab/Chemotherapy for Metastatic Pancreatic Cancer


Advertisement
Get Permission

When the CXCR4 inhibitor BL-8040 was combined with the programmed cell death protein 1 (PD-1) inhibitor pembrolizumab plus chemotherapy in the second-line setting, the regimen showed promising antitumor activity in patients with metastatic pancreatic ductal adenocarcinoma. These findings were presented at the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2019 (Abstract 91O).

Manuel Hidalgo, MD, PhD

Manuel Hidalgo, MD, PhD

Lead investigator Manuel Hidalgo, MD, PhD, Chief of the Division of Hematology and Medical Oncology of Weill Cornell Medicine, shared results from cohort 2 of the multicenter phase IIa COMBAT trial.

Trial Methods

While PD-1 and programmed cell death ligand 1 (PD-L1) inhibitors have shown promise across several types of cancer, they have not shown activity in patients with metastatic pancreatic cancer. Since limited treatment options exist for these patients, Dr. Hidalgo and a team of researchers investigated whether a blockade using BL-8040 and pembrolizumab plus chemotherapy would be effective and safe in these patients.

BL-8040 targets CXCR4 and works by altering the tumor microenvironment to promote the infiltration of effector T cells and decrease the number of immune-suppressor cells. Previous reports demonstrated that the combination of BL-8040, pembrolizumab, and chemotherapy was safe and showed promising overall survival of 7.5 months. These encouraging results together with preclinical data supporting the combination led to expansion of the COMBAT study to include cohort 2, which studied the combination as a second-line therapy in patients with metastatic pancreatic ductal adenocarcinoma.

The patients enrolled on the cohort received 5 days of BL-8040 priming monotherapy followed by combination treatment of chemotherapy with irinotecan/fluorouracil/leucovorin every 2 weeks, pembrolizumab every 3 weeks, and BL-8040 twice a week. Enrolled patients had metastatic pancreatic ductal adenocarcinoma with measurable disease by Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), that had progressed following first-line treatment with gemcitabine-based chemotherapy.

In the cohort of 22 enrolled patients, there were 15 evaluable patients who received at least one dose of the combination and had postbaseline computed tomography. The patients’ median age was 68 years, most had ECOG performance status ≤ 1, and 60% were male.

Results

The best response by RECIST v1.1 for the evaluable population included 4 patients with a partial response and 8 patients with stable disease, which resulted in 12 out of 15 patients achieving disease control. Notably, all of the patients achieving partial response and stable disease showed an initial increase in the marker CA 19-9 followed by a decrease; tumor shrinkage was observed to begin during the transient increase in CA 19-9. Median progression-free survival and overall survival were not yet reached at the time of analysis.

Regarding safety, 15 serious adverse events were reported in 10 patients. Two patients discontinued treatment due to serious adverse events.

The authors suggested that these preliminary data from the ongoing COMBAT study cohort 2 evaluating the triple combination of BL-8040/pembrolizumab/chemotherapy showed promising responses rate and disease control.

Disclosure: This trial was sponsored by Biolinerx. For full disclosures of the study authors, visit oncologypro.esmo.org.


Advertisement

Advertisement



Advertisement