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The 2019 World Conference on Lung Cancer was held September 7 to 10 in Barcelona, Spain. In this podcast, Dr. Vamsidhar Velcheti will discuss a study presented at this meeting that looked at the effects of a new drug targeting a specific genetic change, or mutation, in some people with non-small cell lung cancer.

Dr. Velcheti is Associate Professor and Director of Thoracic Medical Oncology at NYU Langone’s Perlmutter Cancer Center. He is a member of the Cancer.Net Editorial Board and is also the recipient of a 2012 Young Investigator Award and a 2015 Career Development Award from Conquer Cancer, the ASCO Foundation. Dr. Velcheti has no relationships to disclose related to this drug.

ASCO would like to thank Dr. Velcheti for discussing this topic.

Dr. Velcheti: Hi. This is Vamsi Velcheti. I'm the director for the Thoracic Medical Oncology Program at NYU Langone Hospital. And it's my pleasure to discuss an abstract presented at the World Lung Cancer Conference in 2019 in Barcelona. And the abstract I'd like to discuss is treatment with Amgen 510, Amgen five, one, zero, which is a highly selective potent KRAS G12C inhibitor. This was the data presented by Dr.  Ramaswamy Govindan at the World Lung Cancer Conference in Barcelona in 2019.

So KRAS G12C appear as mutations in lung cancer are the most common driver oncogenic mutations. And, in fact, KRAS G12C was one of the first driver oncogenic mutations that was identified in non-small cell lung cancer. However, despite our several efforts to target KRAS G12C with multiple different drugs, we have failed to develop an effective targeted therapy option for patients with KRAS mutations. And this is very much unlike other mutations like EGFR, ELK, ROS, RET. So these mutations have a lot of treatment options for patients with targeted therapy. But unfortunately, that's not the case for KRAS mutation positive lung cancer patients. And KRAS G12C inhibitors like for Amgen 510 have showed us a way forward in terms of developing more effective targeted therapy treatments.

So this abstract presented by Dr. Ramaswamy Govindan at World Lung Cancer Conference is a fierce one, the trial of AMG 510. And in this study, they enrolled all types of solid tumors and predominantly colorectal cancer and lung cancer patients with a specific subtype of KRAS mutations called KRAS G12C. That is a KRAS mutation in the code on G12C. And in this study, they have seen very promising activity, anti-tumor activity in patients with non-small cell lung cancer, especially harboring KRAS G12C mutations. So out of the 76 patients that are enrolled in the study, 34 patients were patients with non-small cell lung cancer harboring KRAS G12C mutations. And out of these 34 patients, there were patients treated in the dose escalation part of the phase I study, meaning they were evaluating the safety of the drug at low doses, and they were escalating the dose in the patient. And there were 15 patients in the study that were treated at the maximum dose that was planned. For the study, which was the 960 milligram dose. So out of our 34 patients that were enrolled in the study, 34 patients with non-small cell lung cancer, most of the patients were heavily pretreated with at least 2 lines of prior treatments. And they were refractory to prior treatments.

So after 34 patients treated with AMG 510, nearly half of the patients had a partial response to treatment. And this is a significant advancement in terms of targeted therapy for KRAS mutant lung cancers. In previous studies with other agents, we have not seen such dramatic responses. And a majority of these responses have been confirmed responses. And the study is very early, and the data presented so far was only from the phase I trial. And there are more patients being enrolled in the ongoing phase II trial with the Amgen 510 in patients with KRAS G12C mutations. And most importantly, this drug seems to be fairly well tolerated and with relatively few treatment-related adverse events. And most of the adverse events were like a grade 1 and 1, with the most common adverse events being diarrhea, nausea, and 1 case of anemia, but has a substantially better safety profile than most other chemotherapy options for patients. So this is a very encouraging study. And we are all looking forward to more of these drugs targeting KRAS G12C and certainly excited to see these early results. And hopefully we'll see more further validation of these exciting early findings in subsequent phase II trials. Thank you very much.

ASCO: Thank you, Dr. Velcheti. Learn more about lung cancer at www.cancer.net/lung. And if this podcast was useful, please take a minute to subscribe, rate, and review the show on Apple Podcasts or Google Play.

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