Onconova Therapeutics Doses First Patient in Phase 1/2a Trial of Narazaciclib Combined with Letrozole in Endometrial Cancer
Prior data provide clinical proof-of-concept for narazaciclib’s mechanism of action in endometrial cancer
Preliminary data from trial’s Phase 1 portion expected in 4Q 2023
NEWTOWN, Pa., May 11, 2023 (GLOBE NEWSWIRE) -- Onconova Therapeutics Inc. (NASDAQ: ONTX), (“Onconova”), a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer, today announced that the first patient has been dosed in the Company’s Phase 1/2a trial evaluating narazaciclib combined with letrozole in recurrent metastatic low-grade endometrioid endometrial cancer (LGEEC). Narazaciclib is a multi-kinase inhibitor targeting CDK 4, CDK 6, and other kinases important for cell proliferation and motility. Preliminary data from the trial’s Phase 1 portion are expected in 4Q 2023.
Endometrial cancer arises in the uterine lining and is the most common cancer of the female reproductive organs. Endometrioid endometrial cancer is the most common subtype of endometrial cancer, accounting for approximately 75% of cases. Data from prior randomized and single-arm trials have demonstrated the anti-cancer activity of letrozole combined with CDK 4/6 inhibition in recurrent endometrial cancer1-3. Currently, there is no health authority-approved CDK 4/6 inhibitor for the treatment of endometrial cancer.
“Improved treatment options for recurrent LGEEC are urgently needed, as the CDK 4/6 inhibitors currently used off-label for this indication are marked by limitations related to safety, tolerability, and treatment resistance,” said Bhavana Pothuri, M.D., Professor, Department of Obstetrics and Gynecology at NYU Grossman School of Medicine and Director, Gynecologic Oncology Research; Perlmutter Cancer Center and Principal Investigator of the trial. “Narazaciclib’s kinase inhibitory profile suggests it can overcome each of these limitations thanks to reduced activity against kinases whose inhibition is associated with bone marrow toxicity and diarrhea, and increased activity against those implicated in pro-tumor immune suppression and cancer cell survival. This hypothesis is supported by data from in vitro and murine cancer models, and I look forward to its continued evaluation in the ongoing Phase 1/2a trial.”
Steven M. Fruchtman, M.D., President and Chief Executive Officer of Onconova, commented, “Our recurrent LGEEC program provides an opportunity to establish narazaciclib as a best-in-class therapy in an indication where clinical proof-of-concept for its mechanism of action has been demonstrated. We, therefore, view the program as a key avenue for value creation and look forward to our Phase 1/2a trial’s preliminary data readout expected later this year.”
About the Phase 1/2a Trial
The Phase 1/2a trial is an open-label, multicenter study evaluating narazaciclib in combination with letrozole as a second or third-line treatment for patients with recurrent metastatic LGEEC. Both narazaciclib and letrozole are administered orally with a continuous daily dosing schedule. The trial begins with a Phase 1 dose escalation phase before moving to a Phase 2 expansion cohort designed to enroll approximately 30 patients. The primary objective of the Phase 1 portion of the trial is to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in order to determine a recommended Phase 2 dose (RP2D) of the combination. The primary objective of the Phase 2 portion will be to evaluate the efficacy of the combination at the RP2D, as measured by progression-free survival at 24 weeks. The estrogen/progesterone receptor status of participants will be recorded as part of an exploratory objective. The trial will be conducted at sites including NYU Langone Health, the site of the Principal Investigator of the study, sites affiliated with MD Anderson Cancer Center, and U.S. Oncology Research sites.
1. Mirza MR. ESMO Virtual Congress 2020. Abstr. LBA28.
2. Konstantinopoulos PA, et al.; 2022 SGO Annual Meeting on Women’s Cancer; March 18-21, 2022. Phoenix, AZ
3. Colon-Otero G, Zanfagnin V, Hou X, et al. ESMO Open. 2020 Oct;5(5):e000926. doi: 10.1136/esmoopen-2020-000926.
About Onconova Therapeutics, Inc.
Onconova Therapeutics is a clinical-stage biopharmaceutical company focused on discovering and developing novel products for patients with cancer. The Company has proprietary targeted anti-cancer agents designed to disrupt specific cellular pathways that are important for cancer cell proliferation.
Onconova’s novel, proprietary multi-kinase inhibitor narazaciclib (formerly ON 123300) is being evaluated in a combination trial with estrogen blockade in advanced endometrial cancer. Based on preclinical and clinical studies of CDK 4/6 inhibitors, Onconova is also evaluating opportunities for combination studies with narazaciclib in additional indications.
Onconova’s product candidate rigosertib is being studied in multiple investigator-sponsored studies, including a dose-escalation and expansion Phase 1/2a study of oral rigosertib in combination with nivolumab in patients with KRAS+ non-small cell lung cancer, and a Phase 2 program evaluating rigosertib monotherapy in advanced squamous cell carcinoma complicating recessive dystrophic epidermolysis bullosa.
For more information, please visit www.onconova.com.
Forward Looking Statements
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