On September 22, 2021 Corvus Pharmaceuticals, Inc. (Nasdaq: CRVS), a clinical-stage biopharmaceutical company, reported an update on its development programs in oncology and infectious disease for mupadolimab (formerly CPI-006), a humanized monoclonal antibody directed against CD73 with a proposed dual mechanism of activating B cells to generate immune responses to viruses and tumor antigens, and inhibiting the production of immunosuppressive adenosine in the tumor micro environment (Press release, Corvus Pharmaceuticals, SEP 22, 2021, View Source [SID1234590167]).
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Corvus is developing mupadolimab as a therapeutic for oncology indications and for infectious disease, starting with COVID-19. Today the Company announced results from its Phase 3 clinical trial of mupadolimab for COVID-19, which have been published online at medRxiv.org. The results, which cover 40 patients that were enrolled in the trial prior to its voluntary discontinuation, suggest improvement in the primary and key secondary endpoints in patients treated with single doses of mupadolimab at 2mg/kg and 1mg/kg compared to placebo. No drug related adverse events were reported in the trial.
"We believe the results from our Phase 3 Covid trial show the potential for a dose response effect on the primary endpoint of time to respiratory failure or death for the 2mg/kg and 1mg/kg mupadolimab cohorts compared to placebo. Secondary endpoints also favored the cohorts receiving mupadolimab. Most interestingly, antiviral responses in the 2mg/kg cohort trended higher across all variants tested, including delta. Cross reactivity to the delta variant is of interest as patients were enrolled prior to its emergence as the dominant variant in the United States," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "As expected when we discontinued the trial, statistical significance was not reached due to the sample size. However, we are very encouraged by the consistent trends and immune response data, which we believe support mupadolimab’s proposed mechanism of action and its potential value for the treatment of viral infections. Combined with the findings in our previous Phase 1 trial in 29 patients, we believe there is mounting evidence that mupadolimab could become a universal treatment for viral diseases, with the ability to address immune escape from variants. We plan to evaluate our next steps with mupadolimab for COVID-19 as we continue to analyze the trial data and explore partnership opportunities to continue its development as a therapeutic."
Mupadolimab also is currently being studied in a Phase 1b/2 clinical study in patients with HPV+ oropharyngeal cancers and non small cell lung cancers (NSCLC) that have failed previous treatment with anti-PD-1 therapy and chemotherapy. Data from the Phase 1b/2 clinical study has been accepted for presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting in November.
"Mupadolimab is one of the most studied anti-CD73 antibodies and is uniquely positioned with a potential dual mechanism, B cell activation and inhibition of immunosuppressive adenosine production," said Dr. Miller. "The complementary mechanisms could result in enhanced immune responses to viral antigens and to tumor antigens. We believe this will enable a unique approach to treating cancers, that can benefit both from removing the adenosine-mediated blockade of the immune system and enhancing immune responses through B cell activation. We look forward to presenting new data from our Phase 1b/2 oncology study at the SITC (Free SITC Whitepaper) meeting in November."
Mupadolimab for COVID-19 Trial Results
This was a randomized, double blind placebo-controlled trial design. In July, Corvus discontinued the clinical trial, which had planned to enroll approximately 1,000 patients, due to positive trends exhibited by COVID-19 vaccines in lowering serious infection and hospitalizations at that time. The discontinuation was not related to any safety or efficacy issues observed in study patients and occurred prior to the recent surge in COVID-19 cases and before the dominant emergence of the delta variant. Of the 40 patients enrolled prior to the discontinuation, 15 received the mupadolimab 2mg/kg dose, 14 received the mupadolimab 1mg/kg dose, and 11 received placebo. Treatment arms were well balanced, except for the 2mg/kg cohort, which had patients with more severe disease on admission with 60% on non-invasive ventilation or high flow oxygen devices, compared to 7% in the 1mg/kg cohort and 27% in the placebo cohort. Data from the three cohorts remained blinded until the final analysis.
The primary endpoint of the clinical trial was the proportion of patients progressing to respiratory failure or death during the 28 days after dosing. In the 2mg/kg cohort, 93.3% of patients were alive and free from respiratory failure, compared to 85.7% in the 1mg/kg cohort and 81.1% in the placebo. The results in the placebo control group were in line with results reported in other randomized trials. In addition, positive trends favoring mupadolimab treatment compared to placebo were seen for all the key secondary endpoints, including time to clinical improvement, time to sustained clinical improvement and time to hospital discharge.
MUPADOLIMAB 2MG/KG AND 1MG/KG VS. PLACEBO
(all received standard of care treatment)
2 MG/KG + SOC
(N=15) 1 MG/KG + SOC
(N=14) PLACEBO + SOC
(N=11)
PRIMARY ENDPOINT:
Free from Respiratory Failure or Death (%) 93.3 85.7 81.1
SECONDARY ENDPOINTS:
Median Days to Improvement (95% CI) 7.0 (4-9) 5.5 (3-14) 11.0 (2-14)
Median Days Sustained Improve (95% CI) 8.0 (4-12) 6.0 (3-14) 11.0 (2-21)
Median Days to Discharge (95% CI) 6.0 (4-12) 4.0 (2-5) 7.0 (2-12)
The results also included anti-viral antibody responses for 26 patients for which pre-treatment and day 28 blood serum are available (8 from the 1mg/kg cohort, 11 from the 2mg/kg cohort and 7 from the placebo cohort). Serum titers in the 2mg/kg cohort appeared to trend higher against the original COVID-19 strain and variants (alpha (B.1.1.7), beta (B.1.351), gamma (P.1) and delta (B.1.617.2), with several patients exhibiting very high titers. Patients in the 2mg/kg cohort demonstrated higher cross-reactivity with the beta, gamma and delta variants compared to 1mg/kg and placebo.