Novel Drugs Are Being Studied in GU Cancers

Charles J. Rosser, MD

Bi-Specific Antibody Targets Prostate Cancer

A bi-specific antibody against both prostate-specific membrane antigen (PSMA) and CD3 for the treatment of prostate cancer is being jointly developed by MorphoSys AG and Emergent BioSolutions Inc, MorphoSys has announced (http://tinyurl.com/kjfksnt).

The compound, a targeted immunotherapeutic protein known as MOR209/ ES414, has been shown in preclinical studies to redirect T-cell cytotoxicity toward prostate cancer cells that express PSMA, an antigen commonly found on such cells. More specifically, the compound selectively binds to the T-cell receptor on cytotoxic T cells and to PSMA on tumor cells, according to the written announcement that appeared on the company’s website in August.

The two companies plan to initiate a phase 1 clinical trial by February that will test MOR209/ES414 in patients with metastatic castration-resistant prostate cancer. Sponsored by Emergent, the trial will be conducted in the United States and Australia.

Experimental Immunotherapy for NMIBC

An immunotherapy targeting non-muscle invasive bladder cancer (NMIBC) is being developed in the clinic by Altor BioScience Corporation with the help of a $1.2 million Small Business Innovation Research grant from the National Cancer Institute. The grant will fund a phase I/II trial that will test the tolerability and efficacy of ALT-803 in patients with the condition.

ALT-803 is a proprietary interleukin-15 superagonist protein complex that has displayed robust antitumor responses in preclinical cancer models, Altor stated in an August announcement about the grant (http:// www.altorbioscience.com/news- 20140819.html).

The drug is capable of “simultaneously activating the innate and adaptive arms of the immune system to elicit both rapid and long-lasting protective responses against hematologic malignancies and solid tumors, including bladder cancer,” according to the statement.

The trial is enrolling at its leading site, the University of Hawaii Cancer Center (UHCC).

“Bladder cancer is an all-too-prevalent disease throughout the world, as well as in the islands of Hawaii. Thus, we are extremely honored to be the lead site in the nation for this groundbreaking clinical trial geared toward improving the lives of patients suffering from bladder cancer,” Charles J. Rosser, MD, the lead clinical investigator at UHCC, said in Altor’s online statement. Hing C. Wong, PhD, Altor’s founder and CEO, added that “Altor is thrilled to receive the recognition and support from NCI to advance the clinical development of ALT-803 for NMIBC. Our objective is to develop ALT-803 in combination with Bacillus Calmette-Guérin as a durable or potentially curative treatment for bladder cancer.”

Hormonal Therapy for Prostate Cancer in Phase III Trial

A phase III trial of ODM-201, a novel oral androgen receptor inhibitor for the treatment of men with prostate cancer, has begun enrollment, sponsors Bayer HealthCare and Finland-based Orion Corporation have announced.

The trial, ARAMIS, will evaluate the drug in men with castration-resistant prostate cancer (CRPC) who have rising prostate-specific antigen (PSA) levels and no detectable metastases, with the aim of determining its effect on metastasis-free survival (MFS). The randomized, multicenter, double-blind, placebo-controlled trial will evaluate the safety and efficacy of oral ODM-201 in patients with non-metastatic CRPC who are at high risk for developing metastatic disease, according to the statement on Bayer’s website (http://tinyurl.com/phc8skc).

ODM-201 is designed to block the growth of prostate cancer cells; it binds to the androgen receptor with high affinity and blocks its cellular function, the statement said. In nonclinical models, Bayer added, ODM-201 has been shown to only minimally penetrate the blood-brain barrier.

Previously, a phase II clinical trial considered three possible doses of ODM-201 in 124 patients with progressive metastatic CRPC, and showed that the compound provided disease suppression and had a favorable safety profile, according to Bayer.

“The field of treatment options for prostate cancer patients is evolving rapidly. However, once prostate cancer becomes resistant to conventional anti-hormonal therapy, many patients will eventually develop metastatic disease,” said Joerg Moeller, MD, a member of the Bayer HealthCare Executive Committee and head of Global Development. “The initiation of a phase III clinical trial for ODM-201 marks the starting point for a potential new treatment option for patients whose cancer has not yet spread and is an important milestone for Bayer in our ongoing effort to meet the unmet needs of people affected by cancer.”