Allarity Therapeutics (“Allarity”) has announced encouraging new results from an ongoing Phase 2 clinical trial of stenoparib, a potential new drug for the treatment of advanced ovarian cancer. Dr Jeremy Graff, President and Chief Development Officer for the company, presented the data at the American Association for Cancer Research (AACR) 7th Biennial Special Conference on Ovarian Cancer in Denver, Colorado in September. 

“Kaplan-Meier analyses show for the first time that median Overall Survival exceeds 25 months for Platinum Resistant and Refractory Ovarian Cancer Patients receiving stenoparib/2X-121 twice daily,” Allarity reported in a press release on the results. Median Overall Survival (mOS) measures the length of time cancer patients stay alive with the disease, and is the FDA’s gold-standard measure for oncology drug approval. At 25 months and counting, stenoparib’s mOS is now nearly 10 months longer than the best outcomes reported with other recently approved therapies for platinum-resistant ovarian cancer.

Ovarian Cancer: Understanding This Gynecological Cancer

Ovarian cancer is the second most common gynecologic cancer in the United States, and causes more deaths than any other cancer of the female reproductive system. This cancer begins in the ovaries, and its early symptoms are often subtle and mistaken for less serious issues. As a result, about 70% of patients are diagnosed only after the disease has already spread.

Ovarian cancer may manifest in ways such as:

• Bloating
• Pelvic and/or abdominal pain
• Nausea and vomiting
• Appetite loss
• Constipation or diarrhea
• Abnormal vaginal bleeding or discharge

Standard treatment for ovarian cancer usually involves a combination of surgery and chemotherapy, most often with a platinum-based drug. These platinum drugs work by causing DNA damage that can kill rapidly-dividing cancer cells. While most patients with newly diagnosed ovarian cancer respond well to platinum-based chemotherapy, with many going into remission, recurrence of the cancer is common. 

When ovarian cancer recurs more than 6 months after finishing treatment with platinum-based drugs, it is considered platinum-sensitive, and so a further round of platinum therapy may still help. If recurrence happens within 6 months, or if the cancer doesn’t respond to platinum therapy at all, the cancer is labeled platinum-resistant, or platinum-refractory. For patients with platinum-resistant or refractory ovarian cancer, treatment options are limited and survival rates are poor, often just over a year with standard therapies.

The Challenges of Past Ovarian Cancer Treatments

In addition to platinum-based chemotherapy, another potential treatment option for ovarian cancer involves drugs known as PARP inhibitors. PARP, short for poly (ADP-ribose) polymerase, refers to the PARP1/2 enzymes cancer cells use to repair damaged DNA.

While platinum-based drugs cause DNA damage in rapidly-dividing ovarian cancer cells, PARP inhibitors fight the cancer by blocking the enzymes cancer cells use to repair this damage. Because the mechanisms of these drugs overlap, with one preventing repair of the damage to cancer cells the other causes, patients who respond well to platinum drugs often also benefit from PARP inhibitors. 

However, in ovarian cancer cases which don’t respond to platinum therapy, the benefits of PARP inhibitors are also limited. This is especially true for patients whose tumors have normal versions of their BRCA1 and BRCA2 genes, genes that are important for DNA repair and help prevent the development of ovarian cancer, among others. Mutations of a cell’s BRCA genes interfere with its ability to carry out DNA repair.

People with ovarian cancer without these mutations, are referred to as having “BRCA wild-type” genes. While carrying a wild-type BRCA gene can help prevent cancer developing initially, BRCA wild-type tumors are less responsive to PARP inhibitors since the vulnerability in the cancer cell’s ability to conduct DNA repair isn’t present.

Stenoparib as an Improvement

Stenoparib, also known as 2X-121, is a twice-daily oral therapy that works in two ways. Like earlier-generation PARP inhibitors, it works by blocking the PARP1/2 enzymes cancer cells use to repair damaged DNA. Stenoparib also inhibits tankyrase 1/2, enzymes which are part of the WNT/β-catenin signaling pathway. The WNT pathway is a cell signalling system implicated in numerous cancers that, when overactive, can drive tumor growth and resistance to treatment.

By hitting both targets, stenoparib could help a broader range of individuals with ovarian cancer, beyond those with a BRCA mutation. In fact, Allarity reported that one of the two patients that have survived on stenoparib more than 24 months has a wild-type BRCA gene. The study population for this trial also included heavily pre-treated patients, many of whom had previously received PARP inhibitors, chemotherapy, immunotherapy, and antibody-drug conjugates (ADCs). In addition to improved mOS, stenoparib continues to show a favorable safety profile, with fewer blood-related side effects than earlier-generation PARP inhibitors.

Continuing Study

The emerging results from this trial 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.”

Although the trial is ongoing, exceeding a 25-month survival mark is a landmark finding for this patient group. Allarity is continuing to study stenoparib under a new Phase 2 trial protocol designed specifically for platinum-resistant or platinum-ineligible ovarian cancer patients. Company representatives remain hopeful that results from the new trial will accelerate efforts toward gaining FDA approval for the drug.

Allarity Therapeutics’ full press release on stenoparib can be accessed here.