ALT-803 and Nivolumab Trial Launches for NSCLC

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It may be that a double-punch approach can be highly beneficial in treating some patients with advanced or metastatic non-small cell lung cancer (NSCLC) who have not been helped in the past.  Researchers are now testing a new combination of drugs that appears to rev up the body’s ability to fight back the disease in a novel way.

Investigators are now enrolling patients in a phase Ib/II study of the checkpoint inhibitor nivolumab (Opdivo) in combination with ALT-803 in patients with pretreated, advanced or metastatic NSCLC. Cancer Immunologist Mark Rubinstein, PhD, at the Medical University of South Carolina (MUSC), helped design the trial and said adding ALT-803 to nivolumab is like adding fuel to a sports car.

“Instead of simply cutting the brake cables of the immune cells using only a checkpoint blocker, we are also adding fuel in the form of ALT-803 so the immune cells will have optimal stimulation and ability to kill tumor cells,” said Dr. Rubinstein, in a MUSC news release.

ALT-803 is a proprietary interleukin-15 (IL-15) superagonist protein complex and is being developed by Altor BioScience Corporation. Preclinical studies have suggested ALT-803 simultaneously mobilizes both the innate and adaptive arms of the immune system to elicit rapid, robust, and long-lasting responses against cancer, according to Altor BioScience Corporation.  

Nivolumab is a fully human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1/PCD-1) with immunopotentiation activity.

Principal study investigator John Wrangle, MD, who is an assistant professor at the Medical University of South Carolina, said this combination therapy approach appears very promising. He said improving immunotherapy is the most important clinical research question being asked today for patients with advanced lung cancer.  

“While recently approved immunotherapies are extremely exciting and better than chemotherapy for second-line therapy, about 80% of patients will not respond,” said Dr. Wrangle.  “By combining two kinds of immunotherapy, we feel we have designed a treatment that is very promising to extend the remarkable benefit experienced by some patients to a larger percentage of people with advanced lung cancer.”

The phase Ib portion of the study hopes to enroll 91 NSCLC patients and it will examine the safety and tolerability of escalating doses of ALT-803 used in combination with nivolumab.  It will also help determine a recommended phase II dose of the combination. The phase II portion of the study will help assess the response rate (using immune-related RECIST) of ALT-803 when combined with nivolumab in patients with advanced and unresectable NSCLC.