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Corvus cancer med presentation disappoints on efficacy

April 4, 2017

Corvus Pharmaceuticals, Inc. (NASDAQ:CRVS), a clinical-stage biopharmaceutical company focused on the development and commercialization of novel immuno-oncology therapies, today announced interim safety and efficacy results from its ongoing Phase 1/1b study. The data showed that treatment with CPI-444 as a single agent and in combination with atezolizumab (Tecentriq®) was well tolerated and resulted in anti-tumor activity in patients with multiple types of advanced solid tumors, including those resistant or refractory to prior treatment with anti-PD-1 or anti-PD-L1 antibodies. CPI-444 is a selective and potent inhibitor of the adenosine A2A receptor. Atezolizumab, developed by Genentech, a member of the Roche Group, is a monoclonal antibody designed to target and bind to a protein called PD-L1 (programmed death ligand-1).

The interim data were presented today in an oral plenary session at the American Association for Cancer Research (AACR) Annual Meeting 2017 in Washington, D.C., by Leisha Ann Emens, M.D., Ph.D., study investigator and associate professor of oncology at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center.

“The data obtained to date are the first report of clinical activity of adenosine receptor blockade in cancer and indicate that CPI-444 provides disease control and induces tumor regression in a number of patients with extensive disease in several tumor types, many of whom are resistant/refractory to prior therapy with an anti-PD-(L)1 antibody,” said Richard A. Miller, an oncologist and co-founder, president and chief executive officer of Corvus. “In addition to the previously announced expansion of the single-agent renal cell cancer cohort, we have expanded three more cohorts — the single agent non-small cell lung cancer patient cohort as well as the renal cell and non-small cell lung cancer patient cohorts treated with the combination therapy.”

Interim safety data on 113 patients and efficacy data for 96 patients enrolled in the study were presented at the AACR conference. Patients with the following histologies were enrolled: 28% triple negative breast cancer (TNBC); 25% non-small cell lung cancer (NSCLC); 12% melanoma (MEL); 12% renal cell cancer (RCC) and 23% others. The median age of the patients was 64 years. All patients had failed approved therapies for their disease, having received a median of two prior treatment regimens (range: 1-5), and 56 percent were resistant or refractory to prior treatment with anti-PD-(L)1 antibodies. Ninety percent of patients had visceral metastases including 37% with liver and 9% with brain metastases.  For patients with RCC and NSCLC, the median number of prior therapies was 4 and 3, respectively.  Seventy nine percent and 75%, of RCC and NSCLC patients, respectively, were resistant/refractory to prior anti-PD-(L)1 therapy. The efficacy endpoints of the study are response rate and disease control rate (defined as complete response, partial response or stable disease).

Interim results showed that disease control (with a median follow up of 16 weeks, range 4-44 weeks) was observed in 38 percent of those receiving CPI-444 as a single agent (N=52) and in 39% of those receiving the combination (N=44), for an overall disease control rate of 38% in 96 evaluable patients. Disease control rates by tumor type and treatment are shown in the following table.

CPI-444

(n=52)

CPI-444 / atezolizumab

(n=44)

All Subjects

(n=96)

All subjects 20 (38%) 17 (39%) 37 (38%)
Prior anti-PD-(L)1 experience

– Naïve

– anti-PD-(L)1 resistant

or refractory

13/29 (45%)

7/23 (30%)

5/18 (28%)

12/26 (46%)

18/47 (38%)

19/49 (39%)

Disease histology

– NSCLC

– MEL

– RCC

– TNBC

– Others

4/14 (29%)

2/5 (40%)

3/5 (60%)

7/17 (41%)

4/11 (36%)

5/10 (50%)

2/6 (33%)

5/5 (100%)

3/14 (21%)

2/9 (22%)

9/24 (38%)

4/11 (36%)

8/10 (80%)

10/31 (32%)

6/20 (30%)

Additional results presented showed:

  • Of 14 patients with tumor regression, three experienced a partial response (reduction of tumor volume > 30% ) and 11 experienced minor tumor regression (change in tumor volume of 0% to reduction of tumor volume ≤ 30%). Nine of these patients were resistant or refractory to prior anti-PD-(L)1 therapy.

    –   The three patients who experienced a partial response included one renal cell cancer patient who received single-agent CPI-444, and one non-small cell lung cancer patient and one colorectal cancer patient who both received the combination therapy

    –   The 11 patients who experienced minor regression of their tumor included seven patients who received single-agent CPI-444 and four who received the combination therapy

  • Of the 37 patients who showed evidence of disease control, 23 remain on treatment
  • CPI-444 has been well tolerated to date. The most common adverse events in patients treated in the single-agent CPI-444 cohorts were Grade 1 and 2 nausea (14%), pruritis (10%), fatigue, abdominal pain, rash, diarrhea, fever, decreased appetite and chills (each 5%). No Grade 3 or 4 adverse events were seen with single agent CPI-444. The most common adverse events in patients treated in the combination cohorts were Grade 1 and 2 nausea (13%), pruritis (9%), fatigue, fever, decreased appetite (each 7%).  In the combination cohorts, three serious adverse events, in two patients, were observed: one patient with Grade 3 Coombs positive autoimmune hemolytic anemia and one patient who experienced both Grade 4 aseptic autoimmune meningoencephalitis and thrombocytopenia. Both cases of these autoimmune toxicities, which have been observed with anti-PD-(L)1 therapies, resolved when treatment was discontinued.

Additional Data Presented in Poster Sessions at AACR

Additional data on CPI-444 will be featured in poster sessions tomorrow at the AACR Annual Meeting as follows:

  • Analysis of tumor biopsies from patients in the Phase 1/1b study showed that CPI-444 alone and in combination with atezolizumab increased frequencies of activated immune cells and increased immune cell infiltration in tumors (Abstract #5593).
  • In preclinical studies, the combination of CPI-444 with an anti-CTLA-4 antibody was synergistic in eliminating tumors and prolonging survival. Similarly, CPI-444 enhanced the activity of multiple targeted and cytotoxic chemotherapy agents with diverse mechanisms that result in cell death and induction of immune infiltration. These findings provide rationale for clinical studies of CPI-444 in combination with additional established immune therapies beyond anti-PD-(L)1 therapy, and in combination with chemotherapy in patients with solid tumors (Abstract #5598).
  • CPI-444 is effective in augmenting efficacy of adoptively transferred T-cells in preclinical vaccine models. CPI-444 as a single agent improved the ratio of CD8 to T-regulatory cells and enhanced T-cell killing in a HER-2/neu expressing animal model by inhibiting the adenosine A2A receptor. These results provide a rationale for expanding CPI-444 into other new modalities of cancer therapy such as vaccines and cell based therapies (Abstract #5579).

Preclinical data on Corvus’ humanized monoclonal anti-CD73 antibody, CPX-006, that is currently in IND-enabling studies will also be presented tomorrow in a poster session (Abstract #5577). Elevated CD73 expression has been observed in human tumors and shown by others to be prognostic in some indications. Corvus’ data shows that CD73 protein is broadly expressed across multiple tumor types in both immune cells and tumor cell compartments and that complete inhibition of CD73 enzyme activity is essential to overcome immune-suppression in vitro. In contrast to other antibodies tested, CPX-006 completely inhibits CD73 catalytic activity in primary human cells and restores T-cell proliferation and cytokine secretion in an adenosine-mediated immunosuppressive environment.

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