A Phase 1/2 Study Evaluating the Efficacy and Safety of the Oral CXCR4 Inhibitor X4P-001 in Combination with Axitinib in Patients with Advanced Renal Cell Carcinoma.

BACKGROUND: X4P-001 is an oral, selective, allosteric inhibitor of the chemokine receptor CXCR4, which is a promising novel target in renal cell carcinoma (RCC). X4P-001 in combination with the tyrosine kinase inhibitor axitinib demonstrated greater than additive anti-tumor activity in xenograft models mediated by decreased myeloid-derived suppressor cell trafficking and reduced proangiogenic signaling.

METHODS: This is a Phase (Ph) 1/2 trial in patients (pts) with advanced clear cell RCC who have failed at least one prior therapy. The safety, tolerability, and recommended Ph 2 dose (RP2D) of X4P-001 in combination with axitinib was established in Ph 1. Here we report results for preliminary efficacy in both the Ph1 dose escalation cohorts and the Ph 2 expansion cohort of pts treated at the RP2D.

RESULTS: The Ph 1 portion of the study is completed and established the combination therapy to be safe and tolerable at the RP2D of 400 mg QD X4P-001 + 5 mg BID axitinib. As of 01 January 2018, data are available for 10 pts in Ph 1 and 41 pts in Ph 2 treated at the daily 400 mg dose (either 200 mg BID or 400 mg QD) of X4P-001 + 5 mg BID axitinib. The median age was 64 years (range 41-87). Patients had received a median of 2 prior lines of systemic therapy (1 line: 29%; ≥ 2 lines: 71%). Seven pts (13.7%) were discontinued from the study due to adverse events (AEs) regardless of relationship. Of the 22 clinically evaluable pts, the objective response rate was 31.8% (1 CR; 6 PR) and the disease control rate was 86.4%. Median duration on treatment was 24 weeks (range 2 - 84). The most common (≥ 10%) treatment-related AEs of any grade were diarrhea, fatigue, hypertension, decreased appetite, dysphonia, nausea, blood creatinine increased, dry eye, headache, and vomiting. Hypertension was the only treatment-related AE (≥ Grade 3) to occur in > 5% of pts (9.8%) and the only serious AE to occur in more than one pt (3.9%).

CONCLUSIONS: Preliminary results from the study demonstrate that X4P-001 + axitinib is clinically active in pts with advanced clear cell RCC and well tolerated with a manageable safety profile. Enrollment in the Ph 2 portion is near-completion and updated study results will be reported. Clinical trial information: NCT02667886.

Journal of Clinical Oncology 36, no. 15. June 01, 2018 [Epub]

Ulka N. Vaishampayan1, David F. McDermott2, Marc Ryan Matrana3, Sun Young Rha4, Amado J. Zurita5, Thai Huu Ho6, Bhumsuk Keam7, Jae-Lyun Lee8, Richard Wayne Joseph9, Sarah Ali10, Walter Michael Stadler11, Naomi B. Haas12, Srinath Sundararajan13, Se Hoon Park14, Rex B. Mowat15, Joel Picus16, Arkadiusz Z. Dudek17, Yousef Zakharia18, Lu Gan19, Michael B. Atkins20

1. Karmanos Cancer Center, Detroit, Michigan
2. Beth Israel Deaconess Medical Center, Boston, Massachusetts
3. Ochsner Clinic Foundation, New Orleans, Louisiana
4. Yonsei University College of Medicine, Seoul, Korea, Republic of (South)
5. The University of Texas MD Anderson Cancer Center, Houston, Texas
6. Mayo Clinic Arizona, Scottsdale, Arizona
7. Seoul National University Hospital - Cancer Research Institute (CRI), Seoul, Republic of Korea
8. University of Ulsan College of Medicine/ Asan Medical Center, Seoul, Korea, Republic of (South)
9. Mayo Clinic, Jacksonville, Florida
10. Michigan State University, Indianapolis, Indiana
11. University of Chicago, Chicago, Illinois
12. Penn Medicine Abramson Cancer Center, Philadelphia, Pennsylvania
13. University of Arizona Cancer Center, Tucson, Arizona
14. Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
15. Toledo Clinic, Toledo, Ohio
16. Washington University in St. Louis School of Medicine, St. Louis, Missouri
17. Health Partners Cancer Care Center, St. Paul, Minnesota
18. University of Iowa Hospitals and Clinics, Holden Comprehensive Cancer Center, Iowa City, Iowa
19. X4 Pharmaceuticals, Cambridge, Massachusetts
20. Georgetown Lombardi Comprehensive Cancer Center, Medstar Georgetown University Hospital, Washington, DC

Journal of Clinical Oncology 36, no. 15; DOI: 10.1200/JCO.2018.36.15_suppl.4510