BioLineRx Ltd. announced encouraging new data from the pilot phase of its CheMo4METPANC Phase 2 clinical trial, showing a 64% overall response rate in first-line pancreatic cancer patients treated with a novel four-drug combination therapy. The results, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, represent a significant improvement over historical response rates for this challenging cancer type.
Strong Efficacy Signals in Pilot Phase
The single-arm pilot study evaluated 11 patients with metastatic pancreatic ductal adenocarcinoma (PDAC) treated with BioLineRx's CXCR4 inhibitor motixafortide combined with the PD-1 inhibitor cemiplimab and standard chemotherapies gemcitabine and nab-paclitaxel. The combination achieved an overall response rate of 64% (7/11 patients) and a disease control rate of 91% (10/11 patients), compared to historical rates of 23% and 48%, respectively, with gemcitabine and nab-paclitaxel alone.
Four of the eleven patients remained progression-free after more than one year, demonstrating sustained clinical benefit. Two patients achieved particularly remarkable outcomes: one experienced complete resolution of all radiologically detected liver lesions and underwent definitive radiation to the primary pancreatic tumor, while another had a sustained partial response and underwent pancreaticoduodenectomy with pathology demonstrating a complete response.
Immune System Activation Observed
Analysis of pre- and on-treatment biopsies and peripheral blood mononuclear cells revealed that CD8+ T-cell tumor infiltration increased across all eleven patients treated with the motixafortide combination. This finding suggests the therapy successfully overcomes the immunosuppressive tumor microenvironment characteristic of pancreatic cancer.
"The data that continue to emerge from the pilot phase of the CheMo4METPANC Phase 2 study are extremely encouraging, with four of eleven patients remaining progression free after more than one year, as well as two patients that underwent definitive treatment, in what has historically been among the most challenging tumor types to treat," stated Philip Serlin, Chief Executive Officer of BioLineRx Ltd.
The analysis also identified a potential biomarker for treatment response: patients achieving partial responses had higher pre-treatment proportions of CXCL12-producing cancer-associated fibroblasts, which could help identify patients most likely to benefit from the therapy.
Trial Expansion and Future Plans
Based on these encouraging pilot results, the CheMo4METPANC Phase 2 trial has been amended to become a randomized study with planned enrollment increasing from 30 to 108 patients. The expanded trial represents the first large, multi-center, randomized study evaluating motixafortide with a PD-1 inhibitor and first-line PDAC chemotherapies.
The randomized portion of the study will compare the four-drug combination against gemcitabine and nab-paclitaxel alone, with progression-free survival as the primary endpoint. Secondary objectives include safety, response rate, disease control rate, duration of clinical benefit, and overall survival. The trial is planned to be fully enrolled by 2027, with a prespecified interim analysis planned when 40% of progression-free survival events are observed.
Addressing Critical Medical Need
Pancreatic cancer represents one of the most challenging malignancies to treat, with poor survival outcomes across all stages. In the United States, an estimated 66,000 adults were diagnosed with pancreatic cancer in 2024, accounting for approximately 3% of all cancers but about 7% of all cancer deaths. For patients initially diagnosed with metastatic disease, who represent 52% of all cases, the 5-year relative survival rate is only 3%.
Mechanism of Action
Motixafortide works by inhibiting CXCR4, a chemokine receptor overexpressed in many human cancers including pancreatic ductal adenocarcinoma. By blocking this receptor, motixafortide modulates the effector/suppressor cell ratio toward a pro-inflammatory profile, enhancing anti-tumor immune activity while reducing pro-tumor immune suppression.
The CheMo4METPANC trial is sponsored by Columbia University and supported equally by BioLineRx and Regeneron. The study's findings will be presented by Dr. Gulam Abbas Manji from Columbia University Herbert Irving Comprehensive Cancer Center at ASCO 2025.
