Apatorsen added to first-line chemotherapy benefits metastatic bladder cancer patients

OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced that results from an exploratory analysis of the Phase 2 Borealis-1™ trial showed that metastatic bladder cancer patients with poor prognostic features benefited from apatorsen 600mg added to first-line chemotherapy compared to chemotherapy alone. Patients in the trial with a Karnofsky Performance Status (KPS) of 80 percent or less, a common indicator of poor prognosis, experienced a 50 percent reduction in risk of death with the addition of apatorsen therapy (OS HR = 0.50). These results were presented in an oral session at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.

"After decades with little progress in the treatment of metastatic bladder cancer, we are finally beginning to see exciting innovation in treatment approaches that may improve outcomes, even in patients with poor prognosis," said Joaquim Bellmunt, MD, PhD, Director, Bladder Cancer Center at the Dana-Farber Cancer Institute, Associate Professor of Medicine at Harvard Medical School, and one of the Primary Investigators of the trial. "This unique approach of combining apatorsen with chemotherapy may lead to a survival benefit in the most vulnerable patients by targeting Hsp27, which is associated with metastasis and treatment resistance."

Borealis-1 was an international, randomized, placebo-controlled trial that evaluated the effect of apatorsen when added to first-line gemcitabine and cisplatin in patients with metastatic bladder cancer. The trial enrolled approximately 180 patients with documented metastatic or locally inoperable transitional cell carcinoma (TCC) of the urinary tract who had not previously received chemotherapy for metastatic disease and were not candidates for potentially curative surgery or radiotherapy. Patients were randomized to receive standard chemotherapy (gemcitabine/cisplatin) in combination with apatorsen at two dose levels (600mg and 1000mg) or gemcitabine/cisplatin plus placebo. The primary endpoint of the trial was overall survival. Secondary endpoints measured disease response as well as safety of each of the two doses of apatorsen.

Exploratory analysis of study results showed that survival outcome was impacted by the following prognostic risk factors: KPS, liver involvement, low hemoglobin and high alkaline phosphatase. Patients who had these poor prognostic features benefited most from 600mg apatorsen therapy. Median overall survival in the poor prognostic group was 11.9 months with 600mg apatorsen + gemcitabine/cisplatin compared to 9 months with gemcitabine/cisplatin alone (OS HR = .77). Importantly, 33 percent of patients in the trial had a KPS less than or equal to 80 percent, which was found to be the single most important risk factor for poor prognosis. These lower KPS, high-risk patients experienced a 50 percent reduction in risk of death (OS HR = 0.50) when 600mg apatorsen was added to chemotherapy.

Overall treatment was well tolerated. Most common Grade ≥3 adverse events (AEs) were neutropenia, anemia, thrombocytopenia and hypertension. Frequency of ≥3 Grade toxicities were: 89 percent (GC), 93 percent (GC+A 600) and 95 percent (GC+A 1000). GC+A 1000 had a higher treatment discontinuation rate due to AEs.

"These results, along with our previous Phase 1 trial in superficial bladder cancer patients who received apatorsen intravesically, demonstrate the potential of this compound across the paradigm of bladder cancer treatment. We are working closely with investigators and plan to engage regulatory agencies to determine next steps," said Scott Cormack, President and CEO of OncoGenex. "The Borealis-1 data underscore the importance of understanding the potential of inhibiting Hsp27 to benefit patients with poor prognosis and those with the most aggressive cancers where patients commonly cycle quickly through all available therapies."

Additionally at ASCO, OncoGenex is presenting data from the Phase 3 SYNERGY trial of its other compound, custirsen, as well as two trials-in-progress posters from the apatorsen ORCA™ (Ongoing Studies Evaluating Treatment Resistance in CAncer) program. The first of these is Borealis-2™, an investigator-sponsored, randomized Phase 2 trial evaluating apatorsen in combination with docetaxel in patients with advanced or metastatic bladder cancer, and who have disease progression following first-line platinum-based chemotherapy. This trial is sponsored by the Hoosier Cancer Research Network and is currently enrolling patients. The second is Cedar™, an investigator-sponsored, randomized, open-label Phase 2 study evaluating apatorsen in previously untreated patients with advanced squamous non-small cell lung cancer (NSCLC). Over the next 12 months, the Company expects a number of significant clinical events from several apatorsen clinical trials within the ORCA™ trial program that are currently evaluating patients in some of the most aggressive tumor types.