Sai-Hong Ignatius Ou, MD, PhD, Health Science Associate Clinical Professor, University of California, Irvine, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, Orange, California, discusses the FDA approval of pembrolizumab (Keytruda) in small cell lung cancer (SCLC).

On June 18, 2019, the FDA granted an accelerated approval to pembrolizumab monotherapy for patients with metastatic SCLC who have disease progression on or after platinum-based chemotherapy and ≥1 other prior line of therapy.

Pooled results from cohorts of the phase II KEYNOTE-158 and phase Ib KEYNOTE-028 trials served as the basis for the approval. Results indicated that the PD-1 inhibitor induced a 19% overall response rate (ORR; (95% CI, 11%-29%) in patients with SCLC who had disease progression on or after platinum-based chemotherapy and ≥1 other prior line of therapy. Nivolumab (Opdivo) is also indicated in this setting, says Ou. It is hard to know how pembrolizumab will be incorporated in the paradigm, pending the results of the KEYNOTE-604 trial which is examining the combination of pembrolizumab and chemotherapy in the frontline setting, he adds. 

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Dr. Ou on the FDA Approval of Pembrolizumab in SCLC

Sai-Hong I. Ou, MD, PhD, professor, Division of Hematology/Oncology, Department of Medicine, University of California Irvine School of Medicine, discusses investigational KRAS inhibitors in lung cancer.

There are 2 direct KRAS G12C inhibitors, including AMG 510 and MRTX849. Both compounds are covalent KRAS inhibitors that bind to the mutated glycine cystine. At this point, they only target 

 mutations, says Ou. By binding to G12C, the compounds try to shift the active form of 

 to the inactive form. Preliminary data were presented on these agents at the 2019 ASCO Annual Meeting showing encouraging activity.

Additionally, there is a SHIP2 inhibitor that targets the GDP and GTP exchange factors. These inhibitors are not specific to 

, which is also in lung cancer, as well as 

 is not limited to lung cancer. Even the 

 G12 mutations are not limited to lung cancer. The SHIP2 inhibitor encompasses a broader spectrum of 

 mutations are typically found in invasive mucinous adenocarcinoma, the primary site of gastrointestinal origin. The 2 SHIP2 inhibitors that are currently in clinical trials include TNO155 and RMC-4630, data for which are expected by the end of 2019.

Sai-Hong I. Ou, MD, PhD

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Dr. Ou on the FDA Approval of Pembrolizumab in SCLC

Dr. Ou on Investigational KRAS Inhibitors in Lung Cancer