On March 20, 2023 Allarity Therapeutics, Inc. (Nasdaq: ALLR) ("Allarity" or the "Company"), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported that it has dosed the first patient in a Phase 1b clinical study evaluating the combination of stenoparib and dovitinib for the treatment of advanced solid tumors, including ovarian cancer (Press release, Allarity Therapeutics, MAR 20, 2023, View Source [SID1234629051]).

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Currently, approximately 70 percent of patients diagnosed with ovarian cancer will experience recurrences.1 However, PARP inhibitors have improved the treatment outlook for many patients who have completed initial treatment with surgery and platinum-based chemotherapy. The strategy underscoring Allarity’s combination of dovitinib and stenoparib is to address the unmet need of ovarian cancer patients, as well as those with other solid tumors, who currently do not benefit from the existing PARP inhibitor treatments.

"Having investigated novel combinations of anticancer agents, including a PARP inhibitor and an anti-angiogenic therapeutic , we have seen improved efficacy. Combining a PARP i nhib i tor with a p an- t yrosine k inase (PTK) i nhibitor , we are also anticipating efficacy in homologous recombination proficient tumors " stated Kathleen N. Moore, MD, MS, Associate Director of Clinical Research, Director of the Oklahoma TSET/Sarah Cannon Phase I Drug Development Unit, Professor of the Section of Gynecologic Oncology at the Stephenson Cancer Center, and the Principal Investigator for Allarity’s Phase 1b study. "I look forward to working with patients and the clinical team at Allarity to determine if the particular combination of dovitinib and stenoparib can provide synergistic therapeutic benefitsand improve outcomes for patients, including those with ovarian cancer."

Study Design

The two-part, open label multicenter Phase 1b program will first evaluate the safety and anti-cancer activity, and determine the maximum tolerated dose (MTD), of stenoparib administered twice a day in participants with advanced solid tumors. The second portion of the study will evaluate safety and anti-cancer activity and determine the MTD of dovitinib when given in combination with the MTD of stenoparib determined in the first cohort.

The Phase 1b trial is designed with a target enrollment of up to 36 patients with advanced solid tumors, focusing on specific tumor types that Allarity anticipates will be most responsive to the drug combination. Researchers will analyze patient tumor samples retrospectively using Allarity’s DRP companion diagnostics for stenoparib and dovitinib. The purpose of this analysis is to further validate the DRP companion diagnostics in advance of an anticipated DRP-guided Phase 2 trial of the dovitinib and stenoparib combination in second line or later metastatic ovarian cancer, targeted for H2 2024.

Study Rationale

Stenoparib is a small molecule, dual-targeted inhibitor of Poly ADP-Ribose Polymerases (PARP 1 and 2) and tankyrase 1 and 2. It works by limiting cancer’s ability to repair single stranded DNA breaks within tumors, which in turn makes tumor cells more vulnerable to death (apoptosis). Dovitinib is a pan-tyrosine kinase inhibitor (pan-TKI), and its mechanisms of action (MOA) works in part to block the formation of new blood vessels that supply a tumor with nutrients and oxygen (anti-angiogenesis), as well as to alter homologous recombination (HR) proficient to HR deficient tumors by down-regulation of HR. As these combined MOAs serve to promote cancer cell vulnerability and restrict blood flow necessary to fuel cancer growth and repair, Allarity believes the combination may cause synthetic lethality, thereby increasing the chances of cancer cell death and providing synergistic, enhanced anti-tumor activity.

"I am very pleased that we have initiated our first combination therapy trial, an important milestone in our pipeline strategy focused on identifying unmet needs in which combination therapies may benefit patients with hard-to-treat cancers ," said James G. Cullem, Allarity’s Chief Executive Officer. "Given that we own both of these assets, the development of this combination benefits from our existing drug supply and manufacturing pathways, and, subject to our ability to raise additional capital to support the study, should enable us to efficiently conduct the Phase 1b dosing portion of the study with an anticipated data readout in the first half of 2024." Mr. Cullem further noted, "Our clinical team, together with Dr. Moore and our Scientific Advisory Board, have smartly designed this Phase 1b study to both identify early signs of therapeutic benefit in likely-to-respond tumor types, as well as to assess the ability of Allarity’s DRP companion diagnostics for stenoparib and dovitinib to identify responder patients."

The initiation of a new combination trial marks a previously-announced shift in the Company’s clinical-stage activities toward development of combination therapies (that are dependent upon the Company’s ability to raise sufficient capital to support these new trials), and reflects the Company’s commitment to delivering innovative treatments that address unmet medical needs and improve patient outcomes.

Allarity holds exclusive, global commercial rights to both dovitinib and stenoparib.

About the Drug Response Predictor – DRP Companion Diagnostic

Allarity uses its drug-specific DRP companion diagnostic to select those patients who, by the genetic signature of their cancer, are found to have a high likelihood of responding to a specific drug. By screening patients before treatment, and only treating those patients with a sufficiently high DRP score, Allarity believes that the therapeutic response rate can be significantly increased. The DRP method builds on the comparison of sensitive versus resistant human cancer cell lines, including transcriptomic information from cell lines combined with clinical tumor biology filters and prior clinical trial outcomes. DRP is based on messenger RNA from patient biopsies. The DRP platform has demonstrated its ability to provide a statistically significant prediction of the clinical outcome from drug treatment in cancer patients in 37 out of 47 clinical studies that were examined (both retrospective and prospective), including ongoing, prospective Phase 2 trials of stenoparib and IXEMPRA. The DRP platform, which can be used in all cancer types and is patented for more than 70 anticancer drugs, has been extensively published in peer reviewed literature.