X4 Pharmaceuticals unveiled data on Saturday from the phase 2 expansion of a study testing its CXCR4 antagonist in combination with Pfizer's Inlyta. The treatment logged a 23% objective response rate (ORR) in patients with clear cell renal cell carcinoma (ccRCC) who had been "heavily pretreated."
The study involved 65 patients with advanced ccRCC, of whom 75% had undergone at least two other therapies before participating in the study. "Well over 90%" of the patients had been treated with tyrosine kinase inhibitors and nearly 50% had received checkpoint inhibitor treatment, X4 CEO Paula Ragan, Ph.D., told FierceBiotech via email. They received a daily 400-mg dose of the candidate, X4P-001-IO and a twice-daily 5-mg dose of Inlyta.
The company said the 23% ORR, observed in 47 evaluable patients, was "encouraging." It "will likely" present data from the remaining 18 patients at ESMO in October and expects the response rate trend to "continue in the same vein," Ragan said.
X4P-001-IO, has the potential to boost clinical responses to Inlyta and other tyrosine kinase blockers that target tumor angiogenesis, the development of new blood vessels in tumors, said lead investigator Ulka Vaishampayan, M.D., chair of the Karmanos Cancer Center and a professor of oncology at Wayne State University, in a statement.
Because around half of the patients in the study are "third line or higher," it's important to contextualize the data, Ragan said.
"In a consortium report on third-line treatments in RCC including axitinib, single-agent targeted therapies were reported to have an average ORR of 10% (range 0%-20%) and mPFS of ~4 months (range 3.6-4.3 months)," she wrote.
"Moreover, the majority of our patients have intermediate or poor prognosis at baseline based on Heng score. For this patient population, duration of response and PFS will be important metrics. Many of our patients are very early on in receiving therapy in our study with X4P-001 and further follow up is necessary to assess clinical benefit and draw conclusions. With this preliminary data, we believe X4P-001 is working and if the current trend holds, we expect it to be compelling."
X4 is also testing X4P-001-IO in tandem with Bristol-Myers Squibb's checkpoint inhibitor Opdivo. Earlier this month, the company announced data from a pilot study showing that adding X4P-001-IO to Opdivo spurred new antitumor activity in patients that had not responded to Opdivo on its own. It is also working on a version of the drug, dubbed X4P-001-RD, for use in patients with WHIM syndrome and other primary immunodeficiencies.