Stenoparib Monotherapy Yields Potential OS Benefit in Platinum-Resistant Ovarian Cancer

Treatment with stenoparib (2X-121; formerly E7449) provided extended clinical benefit in patients with platinum-resistant and -refractory advanced ovarian cancer, according to updated data from an ongoing phase 2 trial (NCT03878849).1

Findings presented at the American Association for Cancer Research (AACR) 7th Biennial Special Conference on Ovarian Cancer showed that at a median follow-up of 21.8 months for patients with a stenoparib-specific drug response predictor (DRP) score above 50 who received stenoparib twice daily (n = 15), the median overall survival (OS) was not reached, and the Kaplan-Meier OS estimate exceeded 25 months.1,2 At the data cutoff date, 2 patients received therapy for longer than 24 months, including 1 patient with BRCA wild-type disease. Overall, investigators observed clinical benefit with stenoparib regardless of patient BRCA mutation status. Additionally, at the data cutoff date, 1 patient with primary platinum-refractory disease remained alive for longer than 2 years after enrollment.

“These emerging clinical results presented at the AACR Special Conference on Ovarian Cancer suggest that stenoparib may offer meaningful extended survival benefit for patients with advanced, platinum-resistant ovarian cancer—a population with historically poor outcomes and limited treatment options,” Thomas Jensen, CEO of Allarity Therapeutics, stated in a news release.1 “Importantly, the durability of clinical benefit—including in BRCA wild-type and heavily pretreated patients—underscores stenoparib’s unique mechanism of action as a dual inhibitor of both PARP and the WNT pathway. Given the FDA’s recent proclamations emphasizing the need to assess OS, we are particularly excited that the median OS in this trial has not yet been reached and exceeds 25 months—that’s nearly 10 months longer than the median OS reported for the most recent FDA approvals and advances in therapy for [patients with] platinum-resistant ovarian cancer.”

What Is the Mechanism of Action of Stenoparib?

Stenoparib is a differentiated, dual PARP1/2 and tankyrase 1/2 small molecule inhibitor. Tankyrases are an attractive therapeutic target in cancer because of the role they play in regulating the WNT signaling pathway, which contributes to the development and progression of certain cancers, including ovarian cancer.

What Was the Original Design of the Phase 2 Trial of Stenoparib in Ovarian Cancer?

The phase 2 trial initially enrolled patients with heavily pretreated disease, defined as 2 or more prior lines of therapy, including those who had previously received PARP inhibitors, immunotherapy, chemotherapy, and antibody-drug conjugates (ADCs).2 Patients needed to have histologically or cytologically documented epithelial ovarian carcinoma and were enrolled independent of platinum response, as long as they had a platinum-free interval of at least 3 months. Patients were also enrolled regardless of BRCA or homologous recombination deficiency status, and they needed to have a DRP score higher than 50.

These patients received stenoparib at 600 mg daily (200 mg in the morning and 400 mg in the evening) until disease progression.

The primary end point in the original trial protocol was overall response rate (ORR). Secondary end points included clinical benefit rate (CBR) at 16 weeks, progression-free survival (PFS), duration of response, OS, correlation of clinical benefit with DRP score, and quality of life.

What Safety Data Have Been Reported From the Phase 2 Trial of Stenoparib in Ovarian Cancer?

Updated safety findings showed that stenoparib continued to have a favorable safety profile, including less myelotoxicity compared with early-generation PARP inhibitors.1,2 The most common adverse effects included anemia (grade 1-4, 21%; grade 3/4, 21%) and neutropenia (7%; 0%).2

What Is the Design of the Updated Phase 2 Trial Protocol for Stenoparib in Ovarian Cancer?

The updated trial protocol is exclusively enrolling patients with platinum-resistant or -ineligible disease who have received no more than 1 additional line of chemotherapy (other than ADCs) after being designated as platinum resistant. Patients are permitted to enroll regardless of BRCA mutation status. Platinum-refractory patients or patients with ascites will be excluded. There are no DRP preselection criteria; DRP will be evaluated retrospectively.

In the updated protocol, patients will be randomly assigned to receive stenoparib at 600 mg (200 mg in the morning plus 400 mg in the evening; n = 20) or 800 mg (400 mg in the morning plus 400 mg in the evening; n = 20) daily.

Key outcomes from the updated protocol include solidifying the stenoparib dose for a pivotal trial, establishing a cut point for DRP preselection in the pivotal trial, ORR, CBR, PFS, and OS.

“We look forward to further exploring the game-changing potential of stenoparib through the ongoing enrollment of patients in our new phase 2 trial protocol expressly enrolling [patients with] platinum-resistant ovarian cancer or platinum-ineligible patients [with ovarian cancer],” Jensen added in the news release.1 “These data will help deepen and solidify the durable clinical benefit and extended OS stenoparib may provide and will support our attempts to accelerate stenoparib toward FDA approval.”

References

1. Allarity Therapeutics presents new phase 2 clinical data for stenoparib/2X-121 showing landmark median overall survival has now surpassed 25 months. News release. Allarity Therapeutics, Inc. September 22, 2025. Accessed September 26, 2025. https://allarity.com/press-release/allarity-therapeutics-presents-new-phase-2-clinical-data-for-stenoparib-2x-121-showing-landmark-median-overall-survival-has-now-surpassed-25-months/
2. Musa F, Knudsen S, Jensen T, et al. 2X-121- a novel, dual inhibitor of PARP and tankyrase- shows promising clinical benefit in a phase 2 trial in advanced, recurrent ovarian cancer patients (NCT#03878849). Presented at: AACR Special Conference on Ovarian Cancer; September 19-21, 2025; Denver, Colorado.