On December 5, 2023 Allarity Therapeutics, Inc. ("Allarity" or the "Company") (Nasdaq: ALLR), a clinical-stage pharmaceutical company developing novel oncology therapeutics together with drug-specific DRP companion diagnostics for personalized cancer care, reported encouraging initial results from its ongoing Phase 2 clinical trial evaluating the efficacy of its PARP inhibitor, stenoparib, in women with advanced ovarian cancer (AOC) (Press release, Allarity Therapeutics, DEC 5, 2023, View Source [SID1234638168]). Of the five evaluable patients included in the initial data analysis, one patient experienced a complete response and the other four demonstrated stable disease.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Investigators prescreened women with AOC using Allarity’s DRP-Stenoparib CDx, a complex transcriptomic signature comprising 414 mRNA biomarkers indicative of response/resistance to the drug. Each woman was assigned a DRP-score, and those with scores above 50%, which suggested a higher likelihood of benefiting from treatment with stenoparib, were selected for treatment. Selected patients received stenoparib in a twice daily (BID) dosing regimen (200 mg morning, 400 mg evening) under a change in protocol, implemented earlier in the year, from prior once-daily dosing of 600 mg. Allarity implemented the protocol change to optimize the drug exposure taking into account the half-life of stenoparib in patients.

Of the 22 patients screened with the DRP-Stenoparib CDx, 17 DRP positive patients were identified. Eleven women have entered treatment, and among the five evaluable participants assessed up to the data evaluation cut-off, there were early signs of clinical benefit in all cases:

One patient experienced a complete response (CR) by scan (to be confirmed by second scan) and by decreased levels of CA125 (a biomarker of AOC).
One patient experienced stable disease with tumor shrinkage of 19%.
One patient experienced stable disease for more than 24 weeks with tumor
shrinkage of 11%.
Two patients experienced stable disease with tumor shrinkage of 8%.
All five patients had previously been treated with another PARP inhibitor. All five patients remain in treatment with stenoparib and the four that did not have complete responses are showing stable disease at this time.

"We are enthusiastic about these early, promising data since the observed clinical benefit indicates that stenoparib is active in advanced ovarian cancer patients selected with the DRP -Stenoparib CDx, even though these women had prior PARP inhibitor therapy and chemotherapy. While still early, these data suggest that BID dosing of this drug, and the use of the DRP -Stenoparib CDx for patient selection and treatment, may provide advanced ovarian cancer patients meaningful benefit. The DRP -Stenoparib CDx, if approved, may provide clinicians with an important diagnostic to guide patient treatment in this hard-to-treat patient population," said Marie Foegh, M.D., Chief Medical Officer of Allarity.

The initial data readout is from an ongoing Phase 2 open-label, single-arm trial that Allarity is conducting at multiple sites in the U.S. and Europe. The goal of the study is to evaluate the anti-tumor effect of stenoparib as monotherapy in DRP-selected patients with locally recurrent or metastatic ovarian cancer after previous PARP inhibitor and chemotherapy treatments. The primary endpoint is objective response rate (ORR). Allarity anticipates an interim data readout in Q1 2024.

The DRP-Stenoparib CDx is a transcriptomic signature comprising 414 mRNA biomarkers that are collectively predictive of tumor sensitivity or resistance to stenoparib. Using the DRP CDx to select likely responder patients while excluding likely resistant ones, Allarity aims to improve the benefit-risk ratio of stenoparib in metastatic or locally advanced ovarian cancer. The initial data from Allarity’s ongoing DRP-guided Phase 2 study of stenoparib suggests that the DRP-Stenoparib CDx may identify a subset of AOC patients previously treated with a PARP inhibitor who may benefit from treatment with stenoparib. The DRP-Stenoparib CDx is a clinical-stage companion diagnostic candidate and has not yet been approved by the U.S. FDA or the EU’s EMA.

All preliminary data are subject to change until the final study data readout. Early trial results may not be a reliable indicator of subsequent trial results based on a larger patient population.

About Stenoparib

Stenoparib is an orally-available, small molecule dual-targeted inhibitor of PARP1/2 and telomerase maintenance enzymes (Tankyrase 1 and 2). At present, tankyrases are attracting significant attention as emerging therapeutic targets for cancer, principally due to their role in the Wnt signaling pathway. Aberrant Wnt/β-catenin signaling has been implicated in the development and progression of multiple cancers, potentially giving stenoparib a unique, dual tumor inhibitory action. Stenoparib was originally developed by Eisai Co. Ltd. and was formerly known under the names E7449 and 2X-121. Allarity has the exclusive, global rights for the development and commercialization of stenoparib.

Some approved PARP inhibitors have recently been shown to be associated with less favorable survival outcomes than initially established. Allarity’s Phase 2 trial data for stenoparib to date shows that the drug has much less myelotoxicity than the FDA approved PARP inhibitors. Specifically, in 42 evaluable women in Phase 2 studies with stenoparib, anemia (21%), neutropenia (2%) and thrombocytopenia (0%) was lower than the approved PARP inhibitor niraparib with anemia 51%, neutropenia in 20% and thrombocytopenia oberved in in 52% of 463 patients. Allarity anticipates that this lower myelotoxicity may make stenoparib a better candidate for combination with other drugs. Allarity is studying the therapeutic potential of stenoparib in combination with dovitinib (a pan-targeted kinase inhibitor) in an ongoing Phase 1b trial, with an anticipated data readout near early Q2 2024. The Company believes that stenoparib may have broad therapeutic potential in combination with other anti-tumor agents.