On April 5, 2019 Trovagene, Inc. (Nasdaq: TROV), a clinical-stage oncology therapeutics company, taking a precision medicine approach to develop drugs that target cell division (mitosis) for the treatment of leukemias, lymphomas and solid tumor cancers, reported updated data following its presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (Press release, Trovagene, APR 5, 2019, View Source;additional-patients-achieve-complete-response-at-two-highest-dose-levels-of-onvansertib-300825206.html [SID1234535017]). Additional data from its ongoing Phase 1b/2 study evaluating onvansertib in combination with standard-of-care chemotherapy in Acute Myeloid Leukemia (AML) demonstrates response to treatment in patients in the dose-escalation phase of the trial who received onvansertib at 27mg/m2 and 40mg/m2. The trial is now enrolling patients at the dose level of 60mg/m2 (approximately a 50% increase) in combination with either LDAC or decitabine.
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The greatest anti-leukemic activity, to-date, has been observed in the onvansertib + decitabine arm, now with 3 of 6 (50%) evaluable patients treated at the two highest dose levels tested to-date (27mg/m2 and 40mg/m2) achieving a complete response (2CR and 1CRi). The first patient in the onvansertib + LDAC arm has achieved a complete response at the highest dose level of 40mg/m2 of onvansertib.
"We are pleased with the response to treatment that we are seeing with onvansertib, as well as how safe and well tolerated it appears to be in this difficult-to-treat relapsed or refractory patient population," said Dr. Thomas Adams, Chief Executive Officer and Chairman of Trovagene. "As we continue advancing our AML trial to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), we look forward to sharing additional readouts on the efficacy and safety of onvansertib and the potential opportunity to bring a much-needed new treatment option to relapsed or refractory AML patients."
About the Ongoing Onvansertib Phase 1b/2 Acute Myeloid Leukemia Trial
The Phase 1b/2 trial (NCT03303339) is a multi-center, open-label trial to evaluate the safety and efficacy of Onvansertib in combination with standard-of-care chemotherapy in AML patients who are ineligible for intensive induction therapy or whose disease is relapsed or refractory. In Phase 1b dose-escalation segment of the trial, the primary objective is to determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D), using a traditional 3+3 design. In Phase 2 the MTD or RP2D will be administered to 32 patients to evaluate preliminary antitumor activity and to continue to evaluate the safety and tolerability of onvansertib in combination with standard-of-care chemotherapy. This trial is being led by Amer Zeidan, MBBS, MHS, assistant professor of Medicine at Yale School of Medicine, and Hematology expert at Yale Cancer Center, and Jorge Cortes, M.D., Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center. The trial is being conducted at nine sites in the U.S.
About Onvansertib
Onvansertib is a first-in-class, 3rd generation, oral and highly-selective adenosine triphosphate (ATP) competitive inhibitor of the serine/threonine polo-like-kinase 1 (PLK 1) enzyme, which is over-expressed in multiple cancers, including leukemias, lymphomas and solid tumors. Separate studies with other PLK inhibitors have shown that inhibition of polo-like-kinases can lead to tumor cell death, including a Phase 2 study in Acute Myeloid Leukemia (AML) where response rates of up to 31% were observed when combined with a standard therapy for AML (low-dose cytarabine-LDAC) versus treatment with LDAC alone with a 13.3% response rate. A Phase 1 open-label, dose escalation safety study of onvansertib has been completed in patients with advanced metastatic solid tumor cancers and published in Investigational New Drugs. The maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) in this trial was 24 mg/m2. Trovagene has an ongoing Phase 1b/2 clinical trial with onvansertib in AML that was accepted by the National Library of Medicine (NLM) and is now publicly viewable on www.clinicaltrials.gov. The NCT number assigned by clinicaltrials.gov for this study is NCT03303339. Onvansertib has been granted Orphan Drug Designation by the FDA in the U.S. and by the EC in the European Union (EU) for the treatment of patients with AML.
Onvansertib targets the PLK1 isoform, only (not PLK2 or PLK3), is orally administered, has a 24-hour drug half-life with only mild to moderate side effects reported. Trovagene believes that targeting only PLK1 and having a favorable safety and tolerability profile, along with an improved dose/scheduling regimen will significantly improve on the outcome observed in previous studies with a former panPLK inhibitor in AML.
Onvansertib has demonstrated synergy in preclinical studies with numerous chemotherapies and targeted therapeutics used to treat leukemias, lymphomas and solid tumor cancers, including FLT3 and HDAC inhibitors, taxanes, and cytotoxins. Trovagene believes the combination of its targeted PLK1 inhibitor, onvansertib, with other compounds has the potential to improve clinical efficacy in Acute Myeloid Leukemia (AML), metastatic Castration-Resistant Prostate Cancer (mCRPC), Non-Hodgkin Lymphoma (NHL), Colorectal Cancer, Triple Negative Breast Cancer (TNBC), as well as other types of cancer.