On December 12, 2022 Corvus Pharmaceuticals, Inc. (Corvus or the Company) (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported updated results from its Phase 1/1b trial of CPI-818, the Company’s ITK inhibitor, which demonstrated its anti-tumor activity in patients with T cell lymphoma (TCL) and its therapeutic potential in Th2 and Th17-mediated autoimmune and allergic diseases (Press release, Corvus Pharmaceuticals, DEC 12, 2022, View Source [SID1234625099]). The data will be presented today in a poster at the 64TH American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, which is taking place in-person and virtually from December 10 to 13, 2022.
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"ITK inhibition with CPI-818 has demonstrated monotherapy anti-tumor activity in highly refractory T cell lymphoma patients, a population with limited and often ineffective treatment options," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "We have seen durable objective tumor responses in four of eleven evaluable patients. Based on the clinical results to-date, we plan to advance CPI-818 into a global Phase 2 clinical trial in T cell lymphoma in mid-2023. The study will be conducted in partnership with Angel Pharmaceuticals, which is responsible for the trial in China, where there is a higher incidence and prevalence of T cell lymphoma. The Phase 1 data also provided in vivo evidence of CPI-818’s ability to modulate immune functions of T cells by blocking both Th2 and Th17 T cells and skewing toward Th1 cells. The effects are important for cancer therapy – Th1 cells are essential for elimination of tumor cells – as well as in autoimmune and allergic diseases given that Th2 and Th17 cells are involved in many of these diseases. The clinical and preclinical findings reported at ASH (Free ASH Whitepaper) suggest that CPI-818 enhances anti-tumor immunity and represents a potential novel approach to immunotherapy. We are advancing CPI-818 across multiple therapeutic areas, starting with a Phase 1 clinical trial in atopic dermatitis, known to be a Th2 driven disease, planned for early 2023."
Dr. Miller concluded, "Overall, we believe the data presented at ASH (Free ASH Whitepaper) provides a strong foundation and rationale for ITK inhibition in lymphoma and certain immune diseases. CPI-818 is the most advanced ITK inhibitor we are aware of and has demonstrated high selectivity for ITK, which we believe has been crucial to achieving the immunomodulatory functions observed in our studies to date and represents a significant achievement of our research and development group. We look forward to providing updates on the development of CPI-818 and our other clinical programs – ciforadenant as a potential first line therapy for metastatic renal cell cancer and Angel Pharmaceutical’s study of mupadolimab in patients with relapsed refractory non-small cell lung cancer and head and neck squamous cell cancers – in the coming months and year."
CPI-818 Phase 1/1b Clinical Trial Key Results Presented at ASH (Free ASH Whitepaper) 2022
CPI-818 is being studied in a Phase 1/1b clinical trial as a single agent therapy in patients with relapsed TCL. As of September 2, 2022, 43 patients were enrolled in the trial across four escalating dosing cohorts: 100, 200, 400 and 600 mg, each being administered twice per day. The 200 mg dose was found to provide plasma drug concentrations that optimally affect T cell differentiation in vitro and correspondingly was found to lead to the most frequent and durable tumor responses in vivo. Accordingly, Corvus identified it as the optimal dose and additional patients are being enrolled in a 200 mg dose cohort of the clinical trial. The Phase 1/1b clinical trial endpoints are safety, pharmacokinetics (PK), immunologic effects and tumor response.
T Cell Lymphoma Interim Data Highlights
13 patients were enrolled in the 200 mg cohort and 11 were evaluable for response. Overall objective responses were seen in 4 of 11 patients. Enrolled patients were heavily pretreated receiving a median of 3 prior therapies. In this group, there was one complete response (CR) lasting 25 months in a patient with peripheral T cell lymphoma (PTCL); one nodal CR lasting 19 months in a patient with cutaneous T cell lymphoma; and two partial responses (PR) ongoing at six and eight months follow up, respectively, in patients with PTCL and anaplastic large cell lymphoma. An additional patient in the 600 mg cohort also had a PR.
No dose limiting toxicities were observed, and a maximally tolerated dose was not reached at doses as high as 600 mg twice per day.
All of the foregoing data was as of September 2, 2022.
Immunologic Effects Interim Data Highlights
As of September 2, 2022, the 200 mg optimal dose was shown to induce Th1 skewing and both Th2 and Th17 blockade based on peripheral blood samples from several patients:
In one patient that had a significant reduction of a large tumor on the abdominal wall, a blood sample analysis demonstrated an increase in blood Th1, a decrease in blood Th17, and a reduction of eosinophil count and IL-5 consistent with Th1 skewing and Th2 blockade. Tumor samples in this patient were also analyzed and showed an increase in terminally differentiated T effector memory cells (TEMRA cells), which are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells.
In four patients (two with PRs, one with stable disease (SD) and one with progressive disease (PD), the change in Th1 and CD8+ TEMRA cells was serially measured over time. The PR and SD patients showed an increase in both Th1 and CD8+ TEMRA cells. Of note, SD and PD patients were lymphopenic at baseline with absolute lymphocyte counts <1,000, highlighting the need for a minimal level of immune competence.
In vitro data demonstrated that CPI-818 induced Th1 skewing and Th2 blockade in a dose-dependent manner that supported the selection of the 200 mg dose. This includes an analysis of peripheral blood samples from 12 healthy volunteers that were stimulated in the presence of various concentrations of CPI-818 and other studies that showed that CPI-818 inhibited Th2 cytokine production from normal CD4+ and Sezary cells.
Other in vitro studies showed that CPI-818 inhibited the production of interleukin 4, 5 and 13 cytokines produced by Th2 cells.
In vivo preclinical studies in mice with transplanted T cell lymphoma showed that CPI-818 led to an increase in infiltration of normal CD8+ T cells in the tumor and inhibition of tumor growth.
The findings of the human and preclinical studies suggest that CPI-818 enhances anti-tumor immunity representing a potentially novel approach to immunotherapy.
Separate from the ASH (Free ASH Whitepaper) presentation, Corvus recently initiated a CPI-818 study in companion dogs with naturally occurring, refractory atopic dermatitis. Early results from this study demonstrated CPI-818’s potential activity in this disease with five out of five treated dogs responding to therapy within 14 days.
Conference Call, Webcast and Presentation Slides
Corvus will host a conference call and webcast today, Monday, December 12, 2022 from 4:30 – 5:30 pm ET to provide an overview of the CPI-818 data that presented at the ASH (Free ASH Whitepaper) meeting, along with providing an update on the Company’s development programs. The conference call can be accessed by dialing 1- 877-300-8521 (toll-free domestic) or 1- 412-317-6026 (international) and using the conference ID 10172958. The live webcast, which will include presentation slides, may be accessed via the investor relations section of the Corvus website. A replay of the webcast will be available on Corvus’ website for 90 days.