Examining Transformation of NSCLC to SCLC in EGFR+ Disease

Ravi Salgia, MD, PhD, medical oncologist, professor, and chair, Department of Medical Oncology & Therapeutics Research, and Arthur & Rosalie Kaplan chair in Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center, discusses the results from a study of LB-100 combined with chemotherapy or immunotherapy to address transformation from non-small cell lung cancer (NSCLC) to small cell lung cancer (SCLC).

The study done at City of Hope (NCT04560972) observed a total of 9 patients with EGFR-positive NSCLC treated with either erlotinib (Tarceva), afatinib (Gilotrif), or osimertinib (Tagrisso) with the goal of evaluating the characteristics and metabolism of SCLC.

The primary end point was to investigate any dose-limiting toxicities with the combination and the secondary end points included objective response rate, duration of overall response, the incidence of adverse events, progression-free-survival, and OS. Findings from the preclinical study led to the phase 1b evaluation of LB-100 with carboplatin, etoposide, and atezolizumab (Tecentriq) for the treatment of untreated extensive-stage SCLC.

Transcription:

0:08 | What we started to study in the laboratory was, are there characteristics of small cell lung cancer, we could take advantage of where we could come back with various therapeutics. We started to study the metabolism in small cell lung cancer, and what we found out was this enzyme, PP2A, was very highly dysregulated.

0:30 | We started to inhibit the PP2A with this compound called LB-100, and what we found importantly is that chemotherapy in combination with LB-100, and immunotherapy in combination with LB-100 was very synergistic. The combinations were killing off the small cell lung cancer cells in the laboratory. We did that in vitro in tissue culture dishes. We also did it as spheroids, which are 3-dimensional surfaces, and we found very dramatic results. So, we went to the mouse model, and we found the same thing. So based on that, we designed this clinical trial of using chemotherapy and immunotherapy in combination with LD-100 for patients with newly-diagnosed extensive-stage small cell lung cancer.