Combination therapy with mavorixafor and axitinib (Inlyta) demonstrated clinical improvement with encouraging median progression free survival in a heavily pretreated advanced clear cell renal cell carcinoma patient population.
The results come from the phase IIa portion of X4 Pharmaceuticals Inc.’s open-label phase I/II clinical trial of mavorixafor (X4P-001) in combination with approved tyrosine kinase inhibitor axitinib in patients with ccRCC.
Axitinib was generally well tolerated with a manageable safety profile. Of the 65 patients in the trial, 49 patients (or 75%) received mavorixafor + axitinib as a third- to ninth-line therapy, having received between two and eight prior therapies with a TKI, immuno-oncology agent, or other systemic therapy. Fifty-seven of the 65 patients in the trial (or 88%) had an intermediate or poor prognosis.
Data were presented Sept. 30 at ESMO.
Overall mPFS across clinically evaluable patients receiving mavorixafor + axitinib (n=62) was 7.4 months. Predefined subpopulations examined patients with immediate prior TKI and IO treatment. Patients treated in the subgroup with immediate prior TKI therapy (n=34) demonstrated an objective response rate (ORR) of 18% and an increased mPFS of 7.4 months.
This is a greater than 50% improvement from the 4.8-month historical mPFS with axitinib alone. Patients treated with mavorixafor + axitinib in the subgroup with immediate prior IO therapy (n=18) had an ORR of 61% and an increased mPFS of 11.6 months. In addition, eight of the 65 patients remain on the combination therapy today, with durations of treatment of 17 months or longer. Results suggest mavorixafor may enhance clinical response to axitinib and other TKIs that target tumor angiogenesis, as well as immunotherapy agents.
“In recent years a growing number of vascular endothelial growth factor (VEGF) TKI-based therapies (e.g., axitinib + pembrolizumab), have improved outcomes for patients with ccRCC. Despite these advances, most patients eventually develop resistance to therapy, and new treatment options are necessary to meet this unmet medical need,” lead investigator David F. McDermott, of Beth Israel Deaconess Medical Center, Harvard Medical School, said in a comment. “In this trial of mavorixafor, a novel CXCR4 pathway inhibitor, and axitinib in patients with metastatic ccRCC who had failed prior therapy, the combination was well tolerated and the anti-tumor activity was encouraging. We look forward to confirming the efficacy of mavorixafor in a randomized trial.”
This phase I/II, multi-center, open-label trial of mavorixafor in combination with axitinib included 65 patients with histologically confirmed advanced ccRCC, all of whom received at least one prior systemic therapy. The safety analyses included 65 patients from phases I/II who were treated with 400 mg mavorixafor (200 mg twice daily or 400 mg once daily) + 5 mg axitinib twice daily. Treatment responses were assessed using RECIST v1.1 (a validated set of criteria to assess changes in tumor burden), every eight weeks from day one for 80 weeks, and then every 12 weeks thereafter, by blinded, independent central review.
