X4’s I-O combination pilot shows new activity compared to Opdivo alone

Test tubes
The combination's pilot study demonstrated stable disease and partial responses in patients that had not previously responded or progressed on Opdivo monotherapy. (University of Michigan School of Medicine/CC BY 2.0)

X4 Pharmaceuticals unveiled results from a pilot study showing that the addition of its CXCR4 antagonist to Bristol-Myers Squibb’s Opdivo spurred new antitumor activity in patients that had not responded to Opdivo treatment alone—laying the groundwork toward proving its combination can boost the effectiveness of anti-PD-1 checkpoint inhibitor immunotherapies.

In the study’s nine patients with advanced clear cell renal cell carcinoma, four had progressed while on single-agent Opdivo (nivolumab). The group’s best response reached stable disease after adding X4’s oral X4P-001-IO treatment, an asset the company acquired from Sanofi.

And of the five who had remained stable on Opdivo, one patient demonstrated a partial response with the combination. The length of treatment ranged from 1 to 10 months, with a median duration of 3.7 months.


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“Because the mechanisms of CXCR4 antagonism and checkpoint inhibition act at different points in the tumor immunity cycle, it is reasonable to consider the potential for synergistic activity,” said Sudha Parasuraman, M.D., chief medical officer of X4 Pharmaceuticals, in a release. The data were presented at the annual meeting of the Association for Cancer Immunotherapy in Mainz, Germany.

Toxicity was acceptable, X4 said, with no life-threatening grade 4 or 5 adverse events, and all grade 3 or serious events were managed with appropriate interventions. The most frequent side effects were diarrhea, nasal congestion, dry eye, headache and cough. Bigger tests will however be needed to really dig into how well this combo can work. 

RELATED: $37.5M in hand, Termeer-backed X4 maps a fast pace on cancer immunotherapy R&D

“This preliminary 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,” said lead investigator David McDermott, M.D., of Beth Israel Deaconess Medical Center and Harvard Medical School.

X4 recently raised $27 million in series B financing to increase its staff and advance formulations of the drug through clinical trials. The company is studying X4P-001 not just in cancer immunotherapy combinations but also in rare diseases including WHIM syndrome, a congenital immunodeficiency disorder that leads to neutropenia.

In a phase 1b study, a combination of X4P-001-IO with Pfizer’s Inlyta (axitinib) boosted the disease control rate to 92%, higher than Inlyta alone, with one of the 14 participants experiencing a complete response unseen in larger trials. X4 is also pursuing research in melanoma and getting the drug across the blood-brain barrier.

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