X4P-001 and Inlyta Combo Shows Promise Against Kidney Cancer, Trial Indicates

X4P-001 and Inlyta Combo Shows Promise Against Kidney Cancer, Trial Indicates

A combination of X4P-001 and Inlyta (axitinib) has shown signs of activity against clear cell renal cell carcinoma (ccRCC) in a Phase 1/2 clinical trial.

X4 Pharmaceuticals, which developed X4P-001, presented the findings in a poster session at the European Society of Medical Oncology Congress in Madrid, Sept. 8-12. It was titled “A Phase 1 dose finding study of X4P-001 (an oral CXCR4 inhibitor) and axitinib in patients with advanced renal cell carcinoma (RCC).

X4P-001 inhibits surface receptor CXCR4, a protein found at high levels in several types of cancer, including melanoma and ccRCC, a type of kidney cancer. Previous studies have shown a link between increased production of CXCR4 and lower cancer patient survival rates.

Researchers are evaluating X4P-001 as a potential treatment for both melanoma and refractory ccRCC.

The Phase 1/2 trial (NCT02667886), which is occurring at 13 centers in the United States, involves ccRCC patients. It is evaluating the safety and cancer-fighting potential of a combination of X4P-001 and Pfizer’s VEGFR inhibitor Inlyta, an approved second-line treatment option. The participants have received at least one previous line of therapy.

Sixteen patients have been enrolled in the Phase 1 part of the trial since April 2017. Researchers randomized them to receive escalating doses of X4P-001 and Inlyta. The X4P-001 doses are 200 mg twice a day, 400 mg once a day, or 600 mg once day. Inlyta is being administered twice a day.

Researchers have determined that the 400-mg dose of X4P-001 is the maximum tolerated, so it will be used in the Phase 2 part of the trial. The 600-mg dose led to moderate to severe adverse effects in two patients, including anorexia, cognitive problems, fatigue, nausea, vomiting, and sleepiness.

In general, the adverse events associated with X4p-001 have included diarrhea, hypertension, headache, difficulty speaking, protein in the urine, dry eye and mouth, joint pain, loss of taste, inflammation of mouth mucosa, and weight loss.

After a median of six months of treatment, researchers were able to assess nine patients for treatment response. Three achieved a partial response and five a stable disease, but the disease of one progressed.

“These data from our Phase 1/2 trial evaluating X4P-001-IO plus Inlyta in ccRCC contribute to our knowledge of the therapeutic potential of CXCR4 inhibition when combined with VEGFR inhibition,” Sudha Parasurman, X4’s chief medical officer, said in a press release. “These results demonstrate that the combination is well tolerated and demonstrates preliminary signs of clinical activity in a heavily pre-treated ccRCC patient population. We look forward to sharing updated data as our trial progresses.”

Researchers are still recruiting participants for the Phase 2 part of the study, which started in May 2017. It will evaluate the safety and effectiveness of X4P-001, both as a stand-alone therapy and in combination with Inlyta.