Advanced Small Cell Lung Cancer Drug Shows Benefits

Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate that binds to a protein highly expressed in about two-thirds of SCLC tumors.

The drug rovalpituzumab tesirine (Rova-T) showed promise during the first in-human clinical trial for patients with advanced small cell lung cancer (SCLC), a disease with a median survival of less than 1 year.

These findings were presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.

Rova-T is an antibody-drug conjugate that binds to the delta-like protein 3 (DLL3) highly expressed in about two-thirds of SCLC tumors. When the drug binds to the tumor cell surface, it acts as a Trojan horse, delivering a toxic payload into the cell.

This payload is considered to be too potent when used as a standalone drug, but is relatively safe when attached to the antibody. Researchers enrolled 74 SCLS patients who progressed after at least 1 therapy into the trial.

There were 60 patients administered doses in the active range of 0.2 to 0.4 mg/kg, 68% of whom had the disease at least stabilize, while 18% saw a significant reduction in tumor size.

There were 26 evaluable patients with tumors that overexpressed DLL3. Of these patients, 89% achieved a stabilization of the disease and 39% had a significant reduction in the tumor.

Twelve of these patients received Rova-T as a third-line of treatment, half had significant tumor reductions, and 92% stabilized. There were 4 patients who lived longer than 6 months, including 2 who lived for at least 18 months.

Adverse events included rash, fluid accumulation, and a low platelet count.

“The goal is always to give the right patient the right drug at the right time, but patients with advanced small cell lung cancer have not benefited from any of the new targeted therapies available to patients with other types of cancer,” said researcher Charles M. Rudin, MD, PhD. “They desperately need new treatment options, so the ability to predict whether a patient might respond to Rova-T by testing their tumor for overexpression of the DLL3 protein is crucial because it may ultimately help us give this drug to the patients most likely to benefit from it, and avoid giving it to patients who won't.”

Future studies with Rova T will focus on patients who express the DLL3 target.

“I encourage all oncology physicians and patients to seek out information about clinical trials, as they often give patients the opportunity to receive new drugs and other therapies years before they are more widely available,” Rudin said. “It's increasingly important to remember that nearly every advance in cancer treatment available today was first evaluated in a clinical trial.”