Opdivo (nivolumab) has shown promise as a treatment for recurring small lung cancer patients who have a lot of genetic errors in their tumors, according to a Phase 1/2 clinical trial.

The CheckMate-032 study (NCT01928394) looked at Opdivo as a stand-alone therapy and in combination with Yervoy (ipilimumab). The technical term scientists use for a lot of genetic errors in tumors, or tumor mutations, is high tumor mutation burden. The research team said tumor mutation burden is a promising biomarker of lung cancer outcomes.

Bristol-Myers Squibb, the company marketing Obdivo and Yervoy, presented the trial results at the International Association for the Study of Lung Cancer (IASLC) 18^th World Conference on Lung Cancer (WCLC) in Yokohama, Japan, Oct. 15-18.

The study covered 401 patients. Its primary goal was to assess patients’ objective — or measurable — response to treatment.

In the stand-alone-therapy part of the trial, patients received 3 milligrams per kilogram of body weight of Opdivo every two weeks. In the combo portion, the dose was 1 mg/kg of Opdivo and 3 mg/kg of Yervoy every three weeks for four cycles.

The objective response rate to Opdivo as a stand-alone therapy was 11 percent of the patients who received it. The rate for the combo group was 22 percent of those treated.

Researchers also analyzed patients’ outcomes by tumor mutation burden. This important biomarker may help scientists predict cancer patients’ response to immunotherapies.

The team divided 211 patients into three tumor mutation burden groups: those with high, medium and low levels of burden.

Twenty-one percent of patients with a high tumor mutation burden responded to Opdivo as a stand-alone therapy. When Opdivo and Yervoy were combined, the high burden group’s objective response rate more than doubled to 46 percent.

The objective response rate of those with a medium tumor mutation burden who received Opdivo only was 7 percent of all patients in the group. It was 5 percent for those with a low burden.

Meanwhile, the response rate of those with a medium burden who received the combo was 16 percent of all patients in the group. The figure was 22 percent in the low burden group.

Sixty-two percent of the high burden group who were treated with the combo survived for a year. The figures were 20 percent of the medium burden group and 23 percent of the low burden group.

The one-year survival rates of those treated with Opdivo only were 35 percent of the high burden grouop, 26 percent of the medium burden group, and 22 percent of the low burden group.

“These exploratory TMB [tumor mutation burden] data from CheckMate -032 are the first to show the potential of using mutation burden to predict response in some patients with the combination of two I-O [immuno-oncology] agents,” Dr. Matthew D. Hellmann, a study investigator from the Memorial Sloan Kettering Cancer Center, said in a press release.

“Further investigation is warranted to explore the application of this marker across lung cancers, and in the setting of both I-O combination and monotherapy,” Hellmann added.

“Based on these exploratory data from CheckMate -032 in previously treated small cell lung cancer, and the growing scientific evidence for this biomarker [tumor mutation burden, or TMB], we continue to investigate TMB to understand its relevance as a marker to potentially predict outcomes with immunotherapy,” said Dr. Nick Botwood, development lead for thoracic cancers at Bristol-Myers Squibb. “We are committed to our ongoing thoracic cancer development program, focused on identifying patients most likely to benefit from immunotherapy.”