Corvus Presents New Data on its Investigational ITK Inhibitor CPI-818 at the American Society of Hematology (ASH) Annual Meeting & Exposition
Updated interim data from CPI-818’s phase 1/1b clinical trial provide evidence supporting its potential as a treatment for T cell lymphomas
New pre-clinical data provide evidence of CPI-818 potential as a treatment for autoimmune lymphoproliferative syndrome (ALPS)
“The CPI-818 data presented at ASH continue to show encouraging anti-tumor activity and also extend its potential for the treatment of auto-immune disorders,” said
CPI-818 is an investigational, orally bioavailable, covalent inhibitor of ITK designed to have low nanomolar affinity. In vitro studies have shown that it potently inhibited T cell receptor signal transduction. The CPI-818 presentations at ASH are outlined below and can be found on the Corvus website on the publications and presentations page.
CPI-818, an Oral Interleukin-2-Inducible T-Cell Kinase Inhibitor, Is Well-Tolerated and Active in Patients with T-Cell Lymphoma (Abstract #2068)
CPI-818 is currently being studied in a Phase 1/1b clinical trial that was designed to select the optimal dose of CPI-818 and evaluate its safety, pharmacokinetics (PK), target occupancy, biomarkers and efficacy. The study employed an adaptive, expansion cohort design, with an initial phase that evaluated escalating doses (100, 200, 400, 600 mg taken twice a day) in successive cohorts of patients, followed by a second phase that is designed to evaluate safety and tumor response to the recommended dose of CPI-818 in disease-specific patient cohorts. By protocol design, treatment is discontinued after one year or upon disease progression. The study enrolled 25 patients from
The poster highlighting updated data from the Phase 1/1b study was presented on
- Of the seven evaluable patients with PTCL, there have been two objective tumor responses as of the cut-off date of
October 5, 2020 (the “Cut-Off Date”):- One patient, who previously failed chemotherapy and high dose chemotherapy with autologous bone marrow transplantation, achieved a complete response (CR) with CPI-818 at month 8 that remained ongoing after 12 months on study. The patient received CPI-818 for 12 months and the CR persisted beyond discontinuation of therapy (per the study protocol, the patient stopped receiving therapy after 12 months on study). As of
December 1, 2020 , this patient was off all therapy for lymphoma and remains disease free at 14+ months. - One patient who failed multiple prior therapies achieved a partial response at four months on therapy and remained on study as of the Cut-Off Date.
- One patient, who previously failed chemotherapy and high dose chemotherapy with autologous bone marrow transplantation, achieved a complete response (CR) with CPI-818 at month 8 that remained ongoing after 12 months on study. The patient received CPI-818 for 12 months and the CR persisted beyond discontinuation of therapy (per the study protocol, the patient stopped receiving therapy after 12 months on study). As of
- Of the 11 evaluable patients with CTCL:
- One patient achieved a complete response in lymph node disease and continued to have stable cutaneous disease at more than 12 months on therapy as of
November 2, 2020 . - Three patients achieved stable disease on therapy for between 3 and 5 months..
- One patient achieved a complete response in lymph node disease and continued to have stable cutaneous disease at more than 12 months on therapy as of
- There was a dose dependent increase in receptor occupancy, with trough occupancy >75% observed at the 200, 400 and 600 mg doses.
- No dose limiting toxicities and no grade 3 or 4 treatment related adverse events were observed as of the Cut-Off Date.
The ITK Inhibitor CPI-818 Blocks Activation of T Cells from Autoimmune Lymphoproliferative Syndrome (ALPS) Patients and Is Active in a Murine Model of ALPS (Abstract #95)
ALPS is a rare genetic disease affecting children that manifests with lymphadenopathy, splenomegaly, cytopenias (low blood counts) and autoimmunity. The disease is caused by a mutation in the Fas gene, which provides instructions for making a signaling protein involved in the induction of apoptosis. The mutation results in immune dysregulation due to abnormally high levels of “double negative” T cells (CD4 and CD8 double negative), which infiltrate the blood, spleen and lymphoid tissues. A similar mutation occurs in Fas-deficient MRL/lpr mice, which are used as a model for this disease. These mice are frequently also used as a model for autoimmune disease.
The oral presentation was delivered on
- ITK was expressed in double negative T cells from ALPS patients.
- In vitro, CPI-818 inhibited the activation of stimulated abnormal double negative T cells in ALPS patients.
- In vivo studies in MRL/lpr mice demonstrated that treatment with CPI-818 reduced lymphadenopathy, splenomegaly, and autoimmune skin and kidney disease.
- The pre-clinical data support the evaluation of CPI-818 in ALPS patients.
About Corvus Pharmaceuticals
About CPI-818
CPI-818 is an investigational small molecule drug given orally that has selectively inhibited ITK (interleukin-2-inducible T-cell kinase) in preclinical studies. It was designed to possess dual properties: to block malignant T-cell growth and to modulate immune responses. ITK, an enzyme, is expressed predominantly in T-cells and plays a role in T-cell and natural killer (NK) cell lymphomas and leukemias, as well as in normal immune function. Interference with ITK signaling can modulate immune responses to various antigens. The Company believes the inhibition of specific molecular targets in T-cells may be of therapeutic benefit for patients with T-cell lymphomas and in patients with autoimmune diseases. The Company is conducting a Phase 1 dose escalation trial in patients with refractory T-cell lymphomas.
One of the main strategic rationales for Corvus’ collaboration with Angel is to gain clinical study synergies and accelerate development timelines, whereby data from patients enrolled in
Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of CPI-818, the Company’s ability to develop and advance product candidates into and successfully complete preclinical studies and clinical trials, including the Company’s Phase 1/1b clinical trial of CPI-818 for certain cancers, the timing of the availability and announcement of clinical data and certain other product development milestones, and the sufficiency of the Company’s cash resources. All statements other than statements of historical fact contained in this press release are forward-looking statements. These statements often include words such as “believe,” “expect,” “anticipate,” “intend,” “plan,” “estimate,” “seek,” “will,” “may” or similar expressions. Forward-looking statements are subject to a number of risks and uncertainties, many of which involve factors or circumstances that are beyond the Company’s control. The Company’s actual results could differ materially from those stated or implied in forward-looking statements due to a number of factors, including but not limited to, risks detailed in the Company’s Quarterly Report on Form 10-Q for the quarter ended
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Source: Corvus Pharmaceuticals, Inc.