Phase 2 Trial Closure Clears a Path for Accelerated Development of Stenoparib in Ovarian Cancer

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A phase 2 clinical trial (NCT03878849) investigating the novel PARP inhibitor stenoparib (2X-121) as monotherapy in patients with advanced recurrent ovarian cancer has been discontinued early to enable and expedite the development of a follow-on clinical trial with FDA regulatory intent. Findings from the phase 2 trial provided adequate clinical proof of concept for the drug in this patient population.¹

All patients enrolled in this trial were required to undergo prescreening with the Allarity Therapeutics Drug Response predictor (DRP®) companion diagnostic (CDx), which delineated the patients in the upper 50% likelihood of responding to stenoparib.^1,2

“Based on the substantial clinical benefit observed in the early stages of the trial, we have achieved proof-of-concept results that surpassed our initial expectations and provided the critical insights we were seeking,” Thomas Jensen, chief executive officer of Allarity Therapeutics, stated in a news release.¹ “Concluding the trial now is the most effective way to re-allocate our financial resources to develop a follow-on trial with the fastest route to regulatory submission for stenoparib. The patients enrolled in this trial are heavily pretreated, having undergone multiple prior treatments, often including PARP inhibitors. It is highly noteworthy that stenoparib, used in patients selected with the DRP CDx, has delivered sustained clinical benefit for such very heavily pre-treated patients in the trial.”

The open-label, multicenter, single-arm phase 2 trial enrolled patients 18 years of age or older with cytologically or histologically confirmed ovarian carcinoma who had received at least 2 prior chemotherapies, including platinum-based chemotherapy, taxanes, anti-angiogenesis inhibitors, and mirvetuximab soravtansine-gynx (Elahere).^2,3 All but 2 enrolled patients had received a prior PARP inhibitor.3 Patients were required to have a platinum-free interval of at least 3 months, an ECOG performance status of 0 or 1, and a life expectancy of more than 16 weeks.²

Patients were excluded from the study if they were currently participating in or previously participated in a study with an investigational agent or investigational device within 2 weeks of giving informed consent for the phase 2 trial; if they were receiving concurrent chemotherapy, radiotherapy, or hormonal therapy for ovarian cancer; and if they had another malignancy, excluding any stage I or II cancer that was deemed by the investigator to be cured or unable to influence overall survival (OS) with stenoparib.

In the original phase 2 trial protocol, stenoparib was administered at 600 mg once daily in 28-day cycles.² Following a 2023 protocol change to optimize stenoparib exposure, which considered the half-life of the drug, patients received the agent on a twice-daily schedule of 200 mg in the morning and 400 mg in the evening.⁴

Overall response rate served as the primary end point of this trial.² Key secondary end points included clinical benefit rate, progression-free survival, duration of response, OS, quality of life measurement, and correlation between DRP levels and clinical outcome.

This trial demonstrated a clinical benefit surpassing 20 weeks with stenoparib in the 5 patients with evaluable data at the initial data analysis cutoff.^3,5 The first patient enrolled in the trial continued treatment for over 10 months.³ Furthermore, 1 patient achieved a complete response, continues to exhibit a confirmed response, and remains on treatment. Durable clinical benefit with stenoparib has been observed in patients with platinum-sensitive or -resistant ovarian cancer regardless of homologous repair or BRCA mutation status.

The discontinuation of the phase 2 trial will not affect the ongoing treatment of currently enrolled patients.¹ Allarity plans to announce more comprehensive data with stenoparib at a later date.

References

1. 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 May 3, 2024. 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
2. Investigation of 2X-121 in patients with advanced ovarian cancer selected by the 2X-121 DRP (PREDICT 2X-121). ClinicalTrials.gov. Updated March 13, 2023. Accessed May 3, 2024. https://clinicaltrials.gov/study/NCT03878849?intr=e7449&rank=3
3. Allarity Therapeutics makes strategic pivot to focus solely on accelerating stenoparib toward regulatory approval in advanced recurrent ovarian cancer. News release. Allarity Therapeutics, Inc. March 27, 2024. Accessed May 3, 2024. https://www.globenewswire.com/news-release/2024/03/27/2853146/0/en/Allarity-Therapeutics-Makes-Strategic-Pivot-to-Focus-Solely-on-Accelerating-Stenoparib-Toward-Regulatory-Approval-in-Advanced-Recurrent-Ovarian-Cancer.html
4. Pipeline: stenoparib (2X-121). Allarity Therapeutics. Accessed May 3, 2024. https://allarity.com/pipeline/stenoparib/
5. Allarity’s early phase 2 stenoparib data indicates clinical benefit in women with advanced ovarian cancer selected with DRP companion diagnostic. News release. Allarity Therapeutics, Inc. December 5, 2023. Accessed May 3, 2024. https://www.globenewswire.com/en/news-release/2023/12/05/2790791/0/en/Allarity-s-Early-Phase-2-Stenoparib-Data-Indicates-Clinical-Benefit-in-Women-with-Advanced-Ovarian-Cancer-Selected-with-DRP-Companion-Diagnostic.html