Next Steps for Investigation of Mobocertinib for EGFR Exon 20+ NSCLC


Danny Nguyen, MD, discusses next steps for research of mobocertinib in patients with EGFR-positive non–small cell lung cancer.

Danny Nguyen, MD, assistant clinical professor at the department of medical oncology & therapeutics research at City of Hope, discusses next steps for research of mobocertinib (Exkivity) in patients with EGFR-positive non–small cell lung cancer (NSCLC).

Mobocertinib was investigated in a phase 1/2 study (NCT02716116), which showed efficacy and a tolerable safety profile for patients with an EGFR exon 20 mutation, leading to accelerated FDA approval. It was only approved following disease progression on platinum-based chemotherapy, but according to Nguyen, an ongoing phase 3 study (NCT04129502) is comparing mobocertinib with carboplatin and pemetrexed in the first line.

Another area of investigation is sequencing mobocertinib and amivantamab (Rybrevant), which is also an EGFR exon 20-targeted agent approved following platinum-based chemotherapy. Nguyen says that it is likely that patients with this mutation will likely receive both agents, but sequencing studies could discover which sequence offers superior efficacy and tolerability.

In addition, he suggests future studies could investigate mobocertinib in combination with other agents such as chemotherapy or targeted therapies to improve efficacy.


0:08 | Next steps for the development of mobocertinib is their ongoing phase 3 study in the first line studying comparing it to carboplatin and pemetrexed. That's ongoing to further characterize the benefit in that setting.

In addition, trying maybe [to sequence] it with the other approved EGFR exon 20 medication amivantamab is a hot topic as well. So one question that gets asked of me a lot is, "Well, which one do we do first?" At this point, there [are] not much data to suggest one over the other [in the] first line, because they both have the same approval, which is post-platinum chemotherapy. I think at this point it is kind of like a moot point where most patients will probably be on both medications at some point anyways, but I think that's going to be a question that people try to answer in the future as well.

1:15 | Other pathways moving forward would probably also include novel combinations as well, so combining mobocertinib with other active agents, such as chemotherapy, or potentially other targeted inhibitors as well.

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