The CXCR4 antagonist BL-8040 in combination with the PD-1 inhibitor pembrolizumab and chemotherapy in the second-line setting showed promising anti-tumour activity in a phase IIa trial of patients with metastatic pancreatic adenocarcinoma (PDAC), according to findings presented at the ESMO Immuno-Oncology Congress 2019 in Geneva, Switzerland (11-14 December).
Lead investigator is Manuel Hidalgo, Chief of the Division of Haematology and Medical Oncology of Weill Cornell Medicine in New York, USA. The findings presented at the ESMO Immuno-Oncology Congress 2019 are from cohort 2 of the multicentre phase IIa COMBAT (NCT02826486) study.
While PD-1/PD-L1 antagonists have shown promise across several types of cancer, they have been ineffective in patients with metastatic PDAC, who generally have a poor prognosis. Since limited treatment options exist for these patients, Dr. Hidalgo and a team of researchers investigated whether a blockade using BL-8040, which targets CXCR4, and pembrolizumab plus chemotherapy would be effective and safe in these patients.
BL-8040 targets CXCRA and works by altering the tumour microenvironment (TME) 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 (OS) 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, wherein the combination of BL-8040, pembrolizumab and chemotherapy would be studied as second-line therapy in patients with metastatic PDAC.
The patients enrolled on the cohort received 5 days of BL-8040 priming monotherapy followed by combination treatment of chemotherapy with Onivyde/5-FU/LV every 2 weeks, pembrolizumab every 3 weeks and BL-8040 twice a week. Enrolled patients had metastatic PDAC with measurable disease by RECISTv1.1 that had progressed following first-line treatment with gemcitabine-based chemotherapy.
The combination provided disease control to 80% of patients with PDAC
In the cohort of 22 enrolled patients, there were 15 evaluable patients who received at least 1 dose of the combination and had post-baseline CT. The patients’ median age was 68, most had ECOG performance status ≤1, and 60% were male.
The best response by RECIST v1.1 for the evaluable population included 4 patients with partial response (PR) and 8 patients with stable disease (SD), which resulted in 12 out of 15 patients achieving disease control. Notably, all of the patients achieving PR and SD showed an initial increase in the marker CA 19-9 followed by a decrease; tumour shrinkage was observed to begin during the transient increase in CA 19-9.
Median progression-free survival and OS were not yet reached at the time of analysis.
Regarding safety, 15 serious adverse events (SAEs) were reported in 10 patients and two patients discontinued treatment due to SAEs.
The authors suggested that these preliminary data from the ongoing COMBAT study Cohort 2 evaluating the triple combination of BL-8040, pembrolizumab, and chemotherapy showed promising responses rate and disease control.
This study may also open the door to immunotherapy combinations that are effective in the population of patients with metastatic PDAC.
This trial was sponsored by Biolinerx.
91O – Hidalgo M, Semenisty V, Bockorny B, et al. A multi-center phase IIa trial to assess the safety and efficacy of BL-8040 (a CXCR4 inhibitor) in combination with pembrolizumab and chemotherapy in patients with metastatic pancreatic adenocarcinoma (PDAC).