Dual PARP/Tankyrase Inhibitor Shows Prolonged OS in Ovarian Cancer

New phase 2 clinical data for stenoparib (2X-121), a novel, orally available, small-molecule dual inhibitor of PARP 1/2 and tankyrase 1/2, suggest that the agent may significantly extend median overall survival (mOS) in patients with heavily pretreated advanced platinum-resistant or refractory ovarian cancer (PROC).¹

Preliminary Kaplan-Meier analyses, presented at the American Association for Cancer Research (AACR) 7th Biennial Special Conference on Ovarian Cancer in Denver, CO, indicated that the mOS for patients receiving stenoparib twice daily has not yet been formally reached but currently exceeds 25 months.

This mOS estimate marks a substantial improvement compared with recent clinical advances and FDA-approved therapies for PROC, which typically show an mOS of approximately 16 to 16.5 months. Furthermore, this observed mOS vastly surpasses the 11.5- to 13-month mOS generally reported for standard chemotherapy in this challenging patient population. The durability of clinical benefit is underscored by the fact that two patients remain actively on therapy for more than 24 months, based on a median follow-up time of nearly 22 months.

“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,” said Thomas Jensen, CEO of Allarity Therapeutics, in a press release. “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.”

How Did the Phase 2 Study Enroll Patients?

The phase 2 trial (NCT03878849) enrolled patients with advanced ovarian cancer who exhibited either platinum-resistant or refractory disease.² A specific enrollment requirement mandated that tumors show a stenoparib-specific Drug Response Predictor (DRP) score exceeding 50. The DRP companion diagnostic platform is designed to select patients who possess a cancer gene expression signature indicating a high likelihood of benefiting from the specific drug, aiming to enhance the therapeutic benefit rate. This platform relies on comparing sensitive vs resistant human cancer cell lines, integrating transcriptomic data, clinical tumor biology filters, and prior clinical trial outcomes. The DRP technology has demonstrated the ability to provide statistically significant prediction of clinical outcomes across numerous cancer studies.¹

How Does Stenoparib Work?

Stenoparib’s unique therapeutic potential is believed to stem from its distinct mechanism as a dual inhibitor, distinguishing it from earlier-generation PARP inhibitors. The agent targets PARP 1/2 as well as tankyrase 1/2. Tankyrases are attracting significant research interest as emerging therapeutic targets in oncology due to their function in regulating the WNT signaling pathway. Aberrant WNT/β-catenin signaling is frequently implicated in the development and progression of various cancers. By simultaneously inhibiting PARP and blocking WNT pathway activation, stenoparib is proposed to offer clinical benefit even in difficult-to-treat subsets.

What Was the Clinical Benefit of Stenoparib?

A critical finding from the updated analyses is the observation of clinical benefit independent of the patient’s BRCA status. Data presented demonstrated clinical benefit in patients with both BRCA wild-type (BRCAwt) and BRCA mutant (BRCAmut) genetics. This is significant because a BRCAwt genetic background typically precludes a durable benefit from traditional PARP inhibitors. Notably, 1 of 2 patients who has remained on therapy for more than 24 months carries a wild-type BRCA gene.

Furthermore, the study included a patient initially diagnosed with primary platinum-refractory disease who remains alive more than 2 years after enrollment, an outcome considered highly uncommon in this particularly aggressive subset.

The study population overall included heavily pretreated patients, many of whom had previously received standard chemotherapy, immunotherapy, antibody-drug conjugates (ADCs), and prior PARP inhibitors.

What Was the Safety Profile?

In terms of safety, stenoparib continues to demonstrate a favorable profile. The data suggest significantly less myelotoxicity compared with earlier-generation PARP inhibitors. This safety distinction is particularly relevant following the 2022 market withdrawal of first-generation PARP inhibitors in heavily pretreated ovarian cancer settings due to a lack of demonstrated long-term survival benefit.

The durable overall survival results align with recent regulatory guidance, specifically the FDA’s draft guidance published in August 2025, which reaffirms overall survival as the most meaningful and objective end point for oncology drug approval.³

What is the Current Status of the Trial?

The updated data were presented from the initial phase 2 protocol, which has since been closed to further enrollment, although enrolled patients who continue to benefit remain on the twice-daily stenoparib administration.¹ To capitalize on the emerging clinical experience with stenoparib in PROC, an amended phase 2 protocol began enrolling patients in summer 2025. This new protocol is specifically designed to accelerate clinical development toward FDA approval by enrolling only platinum-resistant or platinum-ineligible patients.

“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 PROC or platinum-ineligible patients. These data will help deepen and solidify the durable clinical benefit and extended overall survival stenoparib may provide,” Jensen added.

As the data presented are derived from an ongoing trial, analyses may be subject to change as the study fully matures.

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. September 22, 2025. Accessed September 25, 2025. https://tinyurl.com/334p664m

2. Investigation of the Anti-tumor Effect of 2X-121 in Patients With Recurrent, Advanced Ovarian Cancer. ClinicalTrials.gov. Updated August 28, 2025. Accessed September 25, 2025. https://clinicaltrials.gov/study/NCT03878849

3. Approaches to Assessment of Overall Survival in Oncology Clinical Trials. US FDA. August 18, 2025. Accessed September 25, 2025. https://tinyurl.com/35x2me2j