Anti-tumor activity and durability of responses data support advancement of soquelitinib (formerly known as CPI-818) into Phase 3 registrational clinical trial and its potential to address the need for new treatments for peripheral T cell lymphoma (PTCL)
Results confirmed patient eligibility requirements and endpoints planned for soquelitinib Phase 3 clinical trial in PTCL
BURLINGAME, Calif., Dec. 09, 2023 (GLOBE NEWSWIRE) -- Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, today announced new interim data from its Phase 1/1b clinical trial of soquelitinib in patients with relapsed PTCL. Soquelitinib demonstrated durable anti-tumor activity, evidenced by progression free survival, duration of response and overall survival rates that exceed current standard of care therapies for patients with relapsed PTCL. The data continues to support the advancement of soquelitinib into a Phase 3 registrational clinical trial in PTCL.
"We have continued to enroll patients in the soquelitinib Phase 1/1b clinical trial to further confirm the eligibility requirements and design for our planned Phase 3 clinical trial," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "As anticipated, the additional patient data confirm that the number of prior therapies and immunocompetence are important patient eligibility requirements, with an optimum range of =1 to =3 prior therapies. The data also demonstrated anti-tumor activity, and in particular, durable responses, both of which continue to guide our plans to conduct a registration Phase 3 trial in relapsed peripheral T cell lymphoma. Overall, we are eager to initiate the Phase 3 clinical trial given the limited efficacy and challenging safety profile for the currently approved treatment options. If approved, soquelitinib would be the first approved agent for treatment of relapsed PTCL based on a randomized trial."
New Soquelitinib Interim Data from the Phase 1/1b Clinical Trial
Updated interim data as of November 27, 2023 (data shown below in Figures 1-3): A total of 36 patients were enrolled in the Phase 1/1b trial at the optimum 200 mg two-times a day dose, including 21 evaluable patients who would be eligible in the planned registrational Phase 3 clinical trial based on =1 and =3 prior therapies (eligible patient population) and 11 evaluable in the corresponding ineligible population based on ?3 prior therapies (ineligible patient population). In the Phase 1/1b clinical trial, the median number of prior therapies was 2 for the eligible patient population and 6 for the ineligible patient population. The rationale for enrolling these patient populations and the stratification analysis was to confirm the eligibility requirements planned for our Phase 3 clinical trial.
- For the eligible patient population, objective responses (complete response, CR plus partial response, PR) were seen in 7 of 21 patients with disease control (CR, PR and stable disease) in 12 of 21 patients. The stable disease group included 5 patients who achieved tumor reductions that did not meet the criteria for a PR, with two of these patients continuing on therapy.
- For the eligible patient population, the median duration of response (DOR) for the seven patients with objective response by Lugano criteria was 14.5+ months (ranged from 6.9-25.2 months); three of these patients continued on therapy.
- A total of five patients in the eligible patient population remained on therapy, including one patient with a CR at 21+ months, two patients with a PR at 3+ and 8+ months, and 2 with stable disease at 3+ and 5+ months.
- Kaplan Meier estimated median progression free survival was 6 months for the eligible patient population.
- Kaplan Meier estimated overall survival at 2 years was 77% for all 36 patients.
- One additional eligible patient, not shown here, was treated at a higher dose and achieved a PR. While in PR, this patient went on to receive a bone marrow transplant and achieved a CR, which has continued as of the data cutoff without any further therapy for 2+ years.
- For the ineligible patient population, no objective responses were seen in 11 evaluable patients.
Figure 1: Waterfall Plot for Patients in the 200 mg Dose Cohort of the Soquelitinib Phase 1/1b Clinical Trial for Peripheral T Cell Lymphoma. The plot shows the best percent change in tumor volume in the 21 evaluable patients (eligible patient population) that were measurable by CT scan or by mSWAT for patients with cutaneous involvement.
Figure 2: Swimmer Plot of Eligible Patient Population (N=21 evaluable, blue) and Ineligible Patient Population (N=11 evaluable, gray). Tumor histologies are also shown. Eligible or ineligible designates whether a patient would qualify for the phase 3 clinical trial.
Figure 3: Table Comparing Soquelitinib Data from Phase 1 (Eligible and Ineligible) to Data Reported for Pralatrexate and Belinostat. Pralatrexate and belinostat received accelerated approval for relapsed PTCL and will be utilized in the standard of care arm of the planned soquelitinib Phase 3 trial. Soquelitinib data are shown for both the eligible and ineligible patient populations from the Phase 1/1b trial reported above. Patient characteristics such as age, number of prior therapies and response to most recent prior therapies for the eligible patient population are similar to those reported for pralatrexate and belinostat. Progression free survival is the primary endpoint for the planned Phase 3 clinical trial; objective response rate and survival are secondary endpoints. The ORR, disease control rate, PFS and OS presented below were not derived from a head-to-head study and are for informational purposes only. Differences exist between trial designs, subject characteristics and other factors, and caution should be exercised when comparing data across unrelated studies.
| Soquelitinib (Phase 1) | Belinostat (BELIEF)1 (N=129) | Pralatrexate (PROPEL)2 (N=111) | ||
| Phase 3 Eligible =1 to = 3 therapies (N=21) | Phase 3 Ineligible > 3 therapies (N=11) | |||
| Age (median) | 60 yrs. | 65 yrs. | 64 yrs. | 58 yrs. |
| Prior Therapies (median) | 2 | 6 | 2 | 3 |
| Response to most recent prior therapy | 39.1% | 23.1% | 41.6% | 36.7% |
| Objective Response Rate | 33.3% | 0% | 25.8% | 29% |
| Disease Control Rate | 57.1% | 45.5% | 40.8% | 48% |
| Progression Free Survival (median) | 6 months | 2.3 months | 1.6 months | 3.5 months |
| Overall Survival at 24 months3 | 77% | ~30% | ~35% | |
| 1 O'Connor O. et. al. J. Clin Onc 33:2492, 2015 | ||||
| 2 O'Connor O. et. al. J. Clin Onc 29:1182, 2011 | ||||
| 3 Includes all 36 enrolled patients | ||||
Molecular Studies on Patient Tumors Support Soquelitinib's Novel Mechanism of Action
Additional new interim data from the Phase 1/1b clinical trial of soquelitinib will be presented today Ning Ding, Ph.D. from Peking University Cancer Hospital & Institute in Beijing, China, in a poster session (abstract #1442) at the 65th American Society of Hematology (ASH) Annual Meeting & Exposition, which is taking place in-person and virtually from December 9-12, 2023. The poster reports on the evaluation of blood samples and tumor biopsies from eight patients who participated in the trial, taken at baseline and during treatment (one patient was sampled during stable disease and again during response, and therefore was counted twice as reflected in the data below). The results support soquelitinib's novel mechanism of action, and demonstrated increases in cytotoxic killer T cells and reductions in markers of T cell exhaustion:
- Responding patients (N=2) showed a sustained increase in CD4+ Th1 cells in the blood and an increase in CD8+ TEMRA cells (T effector memory cells). TEMRA cells are T cells that have responded to an antigen and are able to mediate effector functions, such as the destruction of tumor cells.
- Patients with stable disease (N=4) showed increases in these cell populations that were transient.
- Patients who progress (N=3) showed no increase in these cells.
- Single cell RNA sequencing of tumor biopsies showed soquelitinib treatment increased expression of cytolytic effector molecules and led to a reduction of T cell exhaustion markers.
Dr. Miller added, "We are pleased to see that the molecular studies presented at ASH illustrate the importance of host immune system function and soquelitinib's novel mechanism of action that acts by inducing a host anti-tumor immune response."
The ASH poster is available to ASH attendees in the poster hall and via the virtual event platform, and is also available on the Publications and Presentations page of the Corvus website.
About Corvus Pharmaceuticals
Corvus Pharmaceuticals is a clinical-stage biopharmaceutical company pioneering the development of ITK inhibition as a new approach to immunotherapy for a broad range of cancer and immune diseases. The Company's lead product candidate is soquelitinib, an investigational, oral, small molecule drug that selectively inhibits ITK. Corvus plans to initiate a Phase 3 registrational clinical trial for soquelitinib in patients with relapsed peripheral T cell lymphoma. Its other clinical-stage candidates are being developed for a variety of cancer indications. For more information, visit www.corvuspharma.com.
About Soquelitinib
Soquelitinib (formerly known as CPI-818) is an investigational small molecule drug given orally designed to selectively inhibit ITK (interleukin-2-inducible T cell kinase), an enzyme that is expressed predominantly in T cells and plays a role in T cell and natural killer (NK) cell immune function. The immunologic effects of soquelitinib lead to what is known as Th1 skewing and is made possible by the high selectivity of soquelitinib for ITK. Research on soquelitinib's mechanism of action suggests that it has the potential to control differentiation of normal T helper cells and enhance immune responses to tumors by augmenting the generation of cytotoxic killer T cells and the production of cytokines that inhibit cancer cell survival. Soquelitinib has also been shown to prevent T cell exhaustion, a major limitation of current immunotherapy and CAR-T therapies. Optimal doses of soquelitinib have been shown to affect T cell differentiation and induce the generation of Th1 helper cells while blocking the development of both Th2 and Th17 cells and production of their secreted cytokines. Th1 T cells are required for immunity to tumors, viral infections and other infectious diseases. Th2 and Th17 helper T cells are involved in the pathogenesis of many autoimmune and allergic diseases. The Company believes the inhibition of specific molecular targets in T cells may be of therapeutic benefit for patients with cancers, including solid tumors, and in patients with autoimmune and allergic diseases. Based on interim results from a Phase 1/1b clinical trial in patients with refractory T cell lymphomas, which demonstrated tumor responses in very advanced, refractory, difficult to treat T cell malignancies, the Company plans to initiate a registrational Phase 3 clinical trial of soquelitinib in patients with relapsed PTCL.
Forward-Looking Statements
This press release contains forward-looking statements, including statements related to the potential safety and efficacy of the Company's product candidates including soquelitinib, ciforadenant and mupadolimab; the potential use of soquelitinib to treat a variety of solid tumors and hematological cancers; the Company's ability and its partners' ability, as well as the timing thereof, 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 soquelitinib; and the timing of and the Company's ability to launch clinical trials including the potential registrational Phase 3 clinical trial for soquelitinib. 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 three months ended September 30, 2023, filed with the Securities and Exchange Commission on November 7, 2023, as well as other documents that may be filed by the Company from time to time with the Securities and Exchange Commission. In particular, the following factors, among others, could cause results to differ materially from those expressed or implied by such forward-looking statements: the Company's ability to demonstrate sufficient evidence of efficacy and safety in its clinical trials of soquelitinib and its other product candidates; the accuracy of the Company's estimates relating to its ability to initiate and/or complete preclinical studies and clinical trials and release data from such studies and clinical trials; the results of preclinical studies and interim data from clinical trials not being predictive of future results; the Company's ability to enroll sufficient numbers of patients in its clinical trials; the unpredictability of the regulatory process; regulatory developments in the United States, and other foreign countries; the costs of clinical trials may exceed expectations; and the Company's ability to raise additional capital. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the events and circumstances reflected in the forward-looking statements will be achieved or occur, and the timing of events and circumstances and actual results could differ materially from those projected in the forward-looking statements. Accordingly, you should not place undue reliance on these forward-looking statements. All such statements speak only as of the date made, and the Company undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise.
INVESTOR CONTACT:
Leiv Lea
Chief Financial Officer
Corvus Pharmaceuticals, Inc.
+1-650-900-4522
llea@corvuspharma.com
MEDIA CONTACT:
Sheryl Seapy
Real Chemistry
+1-949-903-4750
sseapy@realchemistry.com
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