X4 Pharmaceuticals, a clinical stage biotechnology company developing novel CXCR4 antagonists to improve immune cell trafficking to treat cancer and rare disease, today announced results from a pilot study of X4P-001-IO in combination with Opdivo® (nivolumab) in patients with clear cell renal cell carcinoma (ccRCC) who are non-responsive to the anti-PD-1 checkpoint inhibitor Opdivo alone. The data will be presented at a Poster Discussion session at the European Society for Medicafl Oncology (ESMO) 2018 Congress, taking place October 19-23, 2018, in Munich, Germany.
"The data from this study demonstrate that the combination with X4P-001-IO and nivolumab has the potential to augment responses in patients who previously received the anti-PD-1 checkpoint inhibitor nivolumab alone," said Toni K. Choueiri, M.D. Director, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, and lead investigator of the study. "This pilot study data requires validation in larger studies as we continue to seek treatments to address the larger population of cancer patients who do not adequately respond to checkpoint inhibitors."
Results were presented from the nine patients with advanced ccRCC enrolled in the pilot study (as of August 1, 2018) who were non-responsive to single agent Opdivo with either stable or progressive disease. Enrolled patients received X4P-001-IO (400 mg, oral, once daily) and continued to receive standard bi-weekly Opdivo therapy. Median duration of treatment with the combination was 3.7 months (range 1-15 months).
Highlights of the data presented at ESMO include:
- X4P-001-IO in combination with Opdivo was tolerable in ccRCC patients. The most frequent drug related adverse events were diarrhea, nasal congestion, ALT/AST increase, dry eye, fatigue. No grade 4 or 5 adverse events occurred. All Grade 3/serious adverse events were manageable with appropriate intervention.
- Combination therapy with X4P-001-IO and Opdivo exhibited anti-tumor activity in some patients with advanced ccRCC who were previously unresponsive to Opdivo monotherapy.
- Four patients who had progressed on prior Opdivo monotherapy had a best response of stable disease with the additional X4P-001-IO to Opdivo treatment.
- Of the five patients who were stable on prior Opdivo monotherapy, one had a partial response with combination therapy of X4P-001-IO and Opdivo.
- Serum biomarker analyses identified significant early changes in cytokines and chemokines, including CXCL9, a chemoattractant ligand for cytotoxic T cell migration.
"These findings add to our clinical experience with X4P-001-IO and our growing understanding of combining CXCR4 antagonists with other agents, such as checkpoint inhibitors," said Ken Gorelick, M.D., Chief Medical Officer of X4 Pharmaceuticals. "X4 continues to explore the important role that CXCR4 antagonism may play in augmenting anti-tumor response in combination with other cancer therapeutic modalities, and therefore, potentially improve outcomes for cancer patients."