Clinical Trials - Trovagene

Focusing on Indications with the Greatest Need for New Cancer Treatment Options

Onvansertib, in combination with already approved therapies, may provide new treatment options for patients across a wide array of cancers

Improving clinical response in patients with AML who are ineligible for induction therapy or who have relapsed/refractory disease

Acute Myeloid Leukemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. There are approximately 20,000 new cases and 10,400 deaths each year, with a five-year survival of 25%.

Onvansertib Clinical Development Program – Phase 1b/2 Open-Label Trial in
Acute Myeloid Leukemia (AML)

Onvansertib is a first-in-class, 3rd generation, oral and highly-selective Polo-like Kinase 1 (PLK1) inhibitor with best-in-class attributes. We are conducting a Phase 1b/2 multi-center, open-label trial of onvansertib in combination with either low-dose cytarabine (LDAC) or decitabine in patients who are not eligible to receive induction therapy or who have relapsed/refractory disease (NCT03303339).

In the 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 anti-tumor 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 Jorge Cortes, M.D., Deputy Department Chair, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center and Amer Zeidan, MBBS, MHS, assistant professor of Medicine at Yale School of Medicine, Hematology expert at Yale Cancer Center. The trial is being conducted at nine sites in the U.S.

Onvansertib in Combination with Either Low-Dose Cytarabine or Decitabine
in Patients with Acute Myeloid Leukemia (AML)

Phase 1b:

Dose escalation to assess safety and identify recommended Phase 2 dose

Phase 2:

Efficacy Endpoint

Rate of complete response (CR + CRi) defined as morphologic leukemia-free state (MLF)

Safety Endpoint

Assess the safety and tolerability of the combination regimen

Exploratory Endpoint

Evaluate pharmacodynamic and correlative biomarkers

Extending the duration of response to Zytiga® (abiraterone acetate)/prednisone in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC)

Metastatic Castration-Resistant Prostate Cancer (mCRPC) affects approximately 25,000 men annually and has a five-year survival rate of 37%. Current treatment is with hormonal therapy, specifically androgen inhibitors, such as Zytiga® (abiraterone acetate). Most patients will develop resistance within 9-15 months of starting treatment and do not generally respond well to subsequent therapies. Thus, there is an ongoing need to increase the duration of response to treatment.

Preclinical studies have demonstrated synergy when onvansertib and Zytiga® are given together and PLK1 inhibition by onvansertib appears to improve Zytiga® efficacy by repressing the androgen signaling pathway.

Trovagene has entered into an exlusive patent license agreement with the Massachusetts Institute of Technology (MIT) to develop combination therapies that include anti-androgen or androgen antagonist and a Polo-like Kinase (PLK) Inhibitor for the treatment of cancer. The unique synergy between anti-androgen and PLK inhibitor combination therapies for inducing tumor cell death may represent a new treatment paradigm. The combination therapies can be used to improve the initial efficacy of one or the other of the active agents, or to re-sensitize cells that have become resistant to one of the active agents when administered alone.

Onvansertib Clinical Development Plan – Phase 2 Open-Label Trial in metastatic Castration-Resistant Prostate Cancer

In our ongoing Phase 2 open-label trial (NCT03414034) of onvansertib in combination with Zytiga®, the primary efficacy endpoint is the proportion of patients who achieve disease control following 12-weeks of treatment, as defined by the lack of prostate specific antigen (PSA) progression.

This trial is being conducted at Beth Israel Deaconess Medical Center (BIDMC), Dana Farber Cancer Institute (DFCI) and Massachusetts General Hospital (MGH), under principal investigator, David Einstein, MD, Genitourinary Oncology Program at BIDMC.

Onvansertib in Combination with Zytiga® and Prednisone in Patients
with Metastatic Castration-Resistant Prostate Cancer (mCRPC)
Dosing Regimen
Onversitab 24 mg/m2
Days 1-5 (21-Day Cycle)
+ Zytyga®/prednisone daily

Duration
4 Cycles = 12 Weeks

Efficacy Endpoint
Disease Control
based on PSA level

Efficacy Endpoint

Effect of onvansertib in combination with Zytiga®/prednisone on disease control assessed by prostate-specific antigen (PSA) decline or stabilization pre- and post-treatment

Safety Endpoint

Safety of onvansertib in combination with Zytiga®/prednisone

Exploratory Endpoint

Target inhibition of PLK1, evaluation of relevant biomarkers that correlate with patient response