4961 - A Phase 2a Trial to Assess the Safety and Efficacy of BL-8040 and Pembrolizumab in Patients with Metastatic Pancreatic Adenocarcinoma (PDAC)

Background

Current treatment options for PDAC patients are limited by poor survival and toxicity. Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis are successful in treating several cancer types; however, PDAC remains refractory. In PDAC mouse models, blockade of the CXCR4/CXCL12 axis promotes tumor infiltration of T cells and synergistic anti-tumor effects when combined with anti-PD-1/anti-PD-L1. We have shown that the high affinity CXCR4 antagonist BL-8040 given as monotherapy promoted infiltration of T cells into metastatic liver lesions in PDAC patients. Here, we report efficacy data from this ongoing Phase 2a clinical trial designed to assess the ability of BL-8040 to enhance responsiveness to the anti-PD-1 ICI Pembrolizumab in patients with metastatic PDAC.

Methods

Phase 2a study consisting of 5 days BL-8040 monotherapy followed by repeated 3-week cycles of Pembrolizumab Q3W in combination with BL-8040 TIW for up to two years. Eligibility criteria included second line (2L) or higher metastatic PDAC with measurable disease by RECIST1.1.

Results

As of May 2018, 37 patients were enrolled in the study of which 29 were evaluable (i.e. received at least one dose of combination and have a post baseline CT) and 17 received one previous treatment line (2L). Response by RECIST1.1 for the evaluable population showed 1 subject (3.4%) with partial response and 9 (31%) with stable disease, yielding 34.5% (10 subjects) with disease control. Mismatch repair status is available for 5 patients with disease control, and all are microsatellite stable (MSS). The most common adverse event was injection site reaction (mild to moderate). Median overall survival (OS) in the entire population and in the 2L subgroup is 3.4 and 7.5 months, respectively, with 6-month survival rates of 34.9% and 50.4%, respectively.

Conclusions

PDAC treatment with BL-8040 and Pembrolizumab is safe, tolerable and shows promising OS, particularly in the 2L subgroup of patients that demonstrated median OS of 7.5 months. This is in comparison to the 6.1 months OS of Onivyde + 5-FU/Leucovorin (approved 2L chemotherapy; NAPOLI-1 trial). Furthermore, these results were seen in MSS subjects, resistant to ICIs as single agents.

Clinical trial identification

NCT02826486.

Legal entity responsible for the study

BioLineRx Ltd.

Funding

BioLineRx Ltd, Merck & Co., Inc.

Editorial Acknowledgement

Disclosure

M. Hidalgo: Clinical advisory board member for clinical trial: BioLineRx; External consultant: BioLineRx. R. Epelbaum, B.M. Wolpin, S.M. Stemmer, R. Geva, E. Borazanci, M. Borad, K.S. Pedersen, J.O. Park, R. Ramirez: Participation in the clinical trial sponsored: BioLineRx. T. Golan: Participation in the clinical trial sponsored: BioLineRx; Participation in clinical advisory board: BioLineRx. A. Peled: Participation in pre-clinical and clinical testing and analysis: BioLineRx. T.M. Lustig, O. Bohana Kashtan, O. Rosenfeld: Employee: BioLineRx; E. Sorani, A. Vainstein Haras: Employee: BioLineRx; Senior management member: BiolineRx. K. Schlienger: Employee: Merck. D.D. Von Hoff: External consultant: BioLineRx.