Phase 1 Trial Indicates Pembrolizumab Safe in Aggressive Small-Cell Lung Cancer

A small phase 1b trial of pembrolizumab in patients with small-cell lung cancer (SCLC) shows that the immunotherapy drug had a favorable safety profile and demonstrated “promising” antitumor activity.

The results, published in the Journal of Clinical Oncology, were part of the KEYNOTE-028 study program, which assesses the use of the monoclonal antibody pembrolizumab in patients with solid tumors that express programmed death ligand 1 (PD-L1). This specific cohort consisted of 24 patients with PD-L1—expressing extensive-stage SCLC who had already received platinum-based therapy.

“With treatment options for SCLC patients receiving platinum-based therapies becoming limited when their disease progresses, it is imperative to explore new therapy options for this population,” explained senior investigator Janice M. Mehnert, MD, in a press statement from Rutgers Cancer Institute of New Jersey, which was one of the trial sites.

In the international trial, participants received pembrolizumab every 2 weeks for 2 years or until they experienced disease progression or intolerable toxicity. Investigators measured the primary endpoints of safety, tolerability, and objective response every 8 weeks for the first 6 months of the trial and every 12 weeks after that.

After a median follow-up of 9.8 months, all 24 patients in the trial had experienced adverse events, with the most common being asthenia (n = 7), fatigue (n = 7), and cough (n = 6). Just 2 patients experienced grade 3 to 5 treatment-related adverse events, indicating more severe effects. Of these, 1 patient had high levels of bilirubin, and the other experienced asthenia, grade 5 colitis, and intestinal ischemia.

According to the study authors, these findings were “consistent with the known safety profile in other tumor types.” They also noted that 7 of the patients demonstrated partial tumor response to pembrolizumab and 1 had a complete response, for an objective response rate of 33%.

“These results also show pembrolizumab demonstrates promising anti-tumor activity in SCLC patients who received prior treatment and have a large presence of the PD-L1 protein in their tumor,” summarized Mehnert in the press statement.

As with other immuno-oncology drugs, scientists are now aiming to determine what characteristics or biomarkers make an SCLC patient more likely to respond to pembrolizumab. Other clinical trials are assessing the safety and efficacy of pembrolizumab for SCLC in combination “with other modes of treatment including chemotherapy, radiation and other immunotherapy regimens,” according to the press release.

Meanwhile, pembrolizumab continues to be tested for not only SCLC, but also other types of cancer. This past May, pembrolizumab was approved as first-line treatment for metastatic nonsquamous non-small cell lung cancer in combination with 2 chemotherapy agents. Safety is still a concern, however: in July, the FDA placed 3 clinical trials of pembrolizumab for multiple myeloma on hold after a pattern of patient deaths.