Novel Therapy in Combination With Opdivo Shows Promise for Lung Cancer Subset

Treatment with Opdivo (nivolumab) in combination with the novel therapy BMS-986012 demonstrated a median overall survival of 18.7 months and a median progression-free survival of 2.1 months among a group of patients with relapsed/refractory small cell lung cancer.

Patients with relapsed/refractory small cell lung cancer (SCLC) who had not yet received treatment with a checkpoint inhibitor achieved “promising” results after receiving the combination of Opdivo (nivolumab) and the anti–fucosyl-GM1 monoclonal antibody BMS-986012, according to data presented at the 2020 World Conference on Lung Cancer.

The data demonstrated that combination induced a greater response to therapy than previous data of Opdivo alone in a similar patient population, according to the study presenter.

“This shows the response rate in 11 out of 29 patients, or 38%, had a full … response,” Dr. Neal Ready, a medical oncologist at Duke Cancer Institute, said during a pre-recorded presentation of the data. “This compares favorably with the historical response rate of 12% reported for monotherapy (Opdivo) in a similar setting.”

This first-in-human, dose-escalation and expansion trial enrolled a total of 29 patients (median age, 65 years; range, 46-79; 52% men) with relapsed/refractory SCLC. All trial participants were White and a significant number of participants (76%) were current or former smokers. To be enrolled on the trial, each patient had to have received at least one prior platinum-based treatment, however patients were excluded from the trial if they previously received treatment with a checkpoint inhibitor.

In the dose-finding phase of the trial, patients received either Opdivo 360 mg every three weeks with either BMS-986012 400 mg (8 patients) or BMS-986012 1,000 mg (8 patients) every three weeks. The phase 1 portion of the trial determined that the ideal dose of BMS-986012 was 400 mg. Once the ideal dose was determined, an additional 13 patients were enrolled. The main goal of the study was to assess the safety of the combination. Other goals of the study were to determine duration of response, as well as survival and response rates.

“We saw the typical immune-related toxicity of (Opdivo) with some additional toxicity related to the anti–fucosyl-GM1 antibody,” said Ready. “They were primarily dermatologic with pruritis [itch] being the most prominent side effect. The pruritis typically started while the drug was being infused, was typically grade 1 or grade 2, and often improved over time.”

The most common treatment-related side effects aside from itch included dry skin (28%), fatigue (28%) and hypothyroidism (17%). Toxicities forced two patients from the 400 mg arm and three patients from the 1,000 mg arm to discontinue treatment.

There were some occurrences of more serious or severe treatment-related side effects. There was one instance each of diarrhea, pancreatitis, increased lipase levels, dehydration, and liver failure.

Of note, Ready said, the duration of response was an “impressive” 26.4 months. Additionally, a patient treated at Duke received 56 cycles of combination therapy over a 38-month period. At the time of data cutoff (July 2020), four patients remained on study therapy.

The median overall survival among all patients in the study was 18.7 months and the median progression-free survival (time during and after treatment where disease doesn’t progress) was 2.1 months.

“These results are promising, although in a small sample size,” Ready said. “The aggregate goals of (BMS-986012) will be studied in an upcoming randomized phase 2 trial in which patients will receive a combination of carboplatin and etoposide and nivolumab, with or without (BMS-986012). Enrollment is planned to start in early 2021.”