Making a dent in advanced refractory cancer

Corvus’ CPI-444 shows promise for disabling a tumor’s ability to subvert attack by the immune system

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BURLINGAME, Calif.—Targeted toward testing new treatments to ultimately beat advanced cancers, West Coast-based clinical-stage biopharmaceutical Corvus Pharmaceuticals Inc. has unveiled a secret weapon: its lead product, CPI-444, a checkpoint inhibitor designed to disable a tumor’s ability to subvert attack by the immune system by inhibiting adenosine.
The latest data, including the preliminary clinical safety and efficacy data from the dose-selection phase of Corvus’ ongoing Phase 1/1b study of CPI-444, were presented Nov. 11 in a poster session by Dr. John Powderly II, founder and president of the Carolina BioOncology Institute, at the recent annual meeting of the Society for Immunotherapy of Cancer (SITC) held in National Harbor, Md.
“Although the data is early, we are seeing encouraging evidence of clinical activity with CPI-444 as a monotherapy and in combination with Tecentriq in patients with advanced refractory cancers,” states Dr. Richard A. Miller, co-founder, president and CEO of Corvus. “We are excited about these preliminary data which show that several patients have achieved stable disease—one of the trial’s primary endpoints—with ongoing responses in cohorts receiving single-agent and combination therapy. Tumor regression has been seen in patients who were naïve and refractory to prior treatments with anti-PD-1 or PD-L1 antibodies.”
Jason Coloma, Corvus’ senior vice president and chief business officer, tells DDNews: “This is the first time it has been demonstrated that an adenosine receptor antagonist has immunomodulatory effects on T cells, as well as showing single-agent activity in PD-(L)1 refractory patients across a number of histologies. Further, targeting the adenosine axis potentially is a novel mechanism of action that could be independent of PD-(L)1.”
The molecule CPI-444 “was originally developed by Vernalis for ADHD and Parkinson’s disease,” he says. “Corvus in-licensed the program and discovered the immunotherapeutic properties and are responsible for moving the program into oncology clinical trials.”
He notes that the company is now enrolling for step two of the Phase 1/1b trial where the researchers will expand cohorts and look for efficacy in particular solid tumor types, including non-small cell lung cancer, melanoma, renal cell carcinoma and triple-negative breast cancer.
The poster at the SITC conference reported that initial safety and efficacy data from the first 46 patients enrolled in the dose-selection phase of the Phase 1/1b trial had a median follow up of two months. All patients had previously failed all approved therapies for their disease, with a median of four prior treatment regimens.
“The data generated in this trial confirms the value of the protocol design and could provide us with an efficient route to future registration trials of CPI-444, particularly as a monotherapy or in combination with anti-PD1/PD-L1 in patients who are refractory to previous treatment with PD1/PD-L1 antibodies,” states Dr. Ginna G. Laport, vice president of clinical development at Corvus.
In a separate poster presentation at SITC, Corvus reported on the effects of treatment with CPI-444 on circulating blood immune cells and T cell clonality. These results indicate:
  • Single-agent treatment with CPI-444 leads to activation of T cells in peripheral blood as well as increases in memory T cells, key mediators of T cell-mediated immune responses.
  • Consistent with this observation, single-agent CPI-444 leads to changes in the repertoire of T cell clones in peripheral blood, consistent with induction of T cell-mediated immune responses. Limited changes in T cell repertoires were seen in patients who progressed on treatment with either CPI-444 alone or in combination with atezolizumab.
  • Changes in T cell repertoires were observed in anti-PD-1/PD-L1 treatment-naïve patients and in patients that were refractory to prior treatment with anti-PD-1/PD-L1 antibodies.
“The biomarker program is generating a wealth of information, and we are encouraged by early data that suggest that CPI-444 treatment results in induction of T cell-mediated immune response in patients,” states Ian McCaffery, vice president of translational sciences at Corvus. “Our goal is to understand the mechanisms of action and changes in patient immune status, and these data suggest that we may be able to identify biomarkers to help define and identify the patients most likely to respond to CPI-444.”

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