The FDA has granted fast track designation to stenoparib (formerly E7449; 2X-121), an investigational, orally available small-molecule inhibitor targeting both PARP1/2 and tankyrase 1/2, for the treatment of patients with advanced ovarian cancer.1
Allarity Therapeutics is developing stenoparib, a differentiated dual-targeted therapy that inhibits DNA repair while disrupting the WNT signaling pathway. The company recently initiated a new phase 2 trial evaluating stenoparib in patients with advanced, recurrent, platinum-resistant or platinum-ineligible ovarian cancer, with the first patient enrolled in June 2025, and several patients have subsequently been dosed.
Previously, a phase 2 clinical trial (NCT03878849) investigating stenoparib as monotherapy in patients with advanced recurrent ovarian cancer was discontinued early to expedite the development of a follow-on clinical trial with FDA regulatory intent.2 Findings from the study provided sufficient clinical proof of concept for stenoparib in this patient population, with a clinical benefit surpassing 20 weeks with stenoparib in the 5 patients evaluable at the initial data analysis cutoff. Notably, all participants were prescreened using the Allarity Therapeutics Drug Response Predictor (DRP) companion diagnostic, which identified patients in the upper 50% likelihood of responding to the therapy.
“We are very pleased that the FDA has granted Fast Track designation to stenoparib,” Thomas Jensen, Chief Executive Officer of Allarity Therapeutics, shared in a news release.1 “This recognition underscores the significant unmet need facing women with advanced ovarian cancer and reflects the potential of stenoparib to meaningfully improve treatment outcomes. We look forward to engaging closely with the FDA as we advance this program.”
Previously Reported Phase 2 Study Overview
The previously discounted dose escalation study was designed to establish the optimal dose of stenoparib as single-agent therapy in patients with recurrent or advanced ovarian cancer.3
Eligible patients had to have histologically confirmed, recurrent advanced ovarian cancer with limited treatment options. They are required to have platinum-resistant disease, defined as progression within 6 months after the last dose of platinum-based chemotherapy, or be considered platinum ineligible due to prior intolerance or contraindications. Additional eligibility criteria include adequate organ function, an ECOG performance status of 0 or 1, and measurable disease per RECIST criteria. Patients may have received prior systemic therapies, provided all treatment-related toxicities have resolved to baseline or grade 1.
Two dosing regimens are being evaluated: 600 mg daily given as 200 mg in the morning and 400 mg in the evening; and a total of 800 mg daily given as 400 mg twice daily. The final dose selection will rely on an integrated analysis of pharmacokinetic and pharmacodynamic data, along with safety and efficacy outcomes.
The exclusion criteria for the 2X-121 trial focus on ensuring patient safety and minimizing factors that could confound study outcomes. Patients are not eligible if they have platinum-refractory disease, defined as progression during their last line of platinum-based therapy, or if they are receiving concurrent chemotherapy, antibody therapy, radiotherapy, hormonal therapy, or other investigational agents (except for certain non–disease-related treatments such as insulin). Those with any malignancy other than stage I and II cancers deemed cured are also excluded. Active infections requiring antibiotic treatment, HIV positivity, or hepatitis B or C infections are disqualifying factors.
Additional exclusion factors cover conditions that could interfere with drug absorption, such as malabsorption syndromes or uncontrolled gastrointestinal issues, as well as the need for immediate palliative surgery or radiotherapy. Patients with uncontrolled ascites requiring drainage greater than 500 cc within 2 weeks, those unable to comply with study protocols for social, psychological, or institutional reasons, and individuals closely related to the sponsor or investigator are also excluded.
The trial’s objectives include evaluating safety and tolerability, assessing preliminary efficacy such as overall response rate and progression-free survival, and characterizing PK/PD parameters to inform dose optimization.
References
- Allarity Therapeutics granted FDA fast track designation for stenoparib for the treatment of advanced ovarian cancer. News Release. Allarity Therapeutics. Accessed August 26, 2025. https://allarity.com/press-release/allarity-therapeutics-granted-fda-fast-track-designation-for-stenoparib-for-the-treatment-of-advanced-ovarian-cancer/
- Allarity Therapeutics’ stenoparib shows clear clinical benefit and achieves significant milestone with early conclusion of phase 2 trial in advanced ovarian cancer. News release. Allarity Therapeutics, Inc. May 2, 2024. Accessed August 26, 2025. https://www.globenewswire.com/news-release/2024/05/02/2874113/0/en/Allarity-Therapeutics-Stenoparib-Shows-Clear-Clinical-Benefit-and-Achieves-Significant-Milestone-with-Early-Conclusion-of-Phase-2-Trial-in-Advanced-Ovarian-Cancer.html
- Investigation of the anti-tumor effect of 2X-121 in patients with recurrent, advanced ovarian cancer. ClinicalTrials.gov. Updated May 8, 2025. Accessed August 26, 2025. https://clinicaltrials.gov/study/NCT03878849