FDA Accelerated Approval of Sunvozertinib: How It Will Shape Treatment for EGFR-Positive NSCLC

Stephen Liu, MD, director of Thoracic Oncology at Georgetown University, joined Lung Cancers Today to discuss the recent FDA accelerated approval of sunvozertinib.

The accelerated approval of sunvozertinib is for the treatment of adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) who have EGFR exon 20 insertion mutations and whose disease has progressed during or after platinum-based chemotherapy.

“The drug retains activity for some of the common mutations as well, but its approval is for that exon 20 space, and it really does shake things up,” Dr. Liu said.

The FDA-recommended dose of sunvozertinib is 200 mg orally once daily with food until disease progression or unacceptable toxicity occurs.

“Importantly, the US approval was for the 200-mg dose. In China, the drug is previously approved at the 300-mg dose, so some slight differences there,” Dr. Liu said. “The 300-mg dose did have a bit more toxicity, though it also did show a little bit more efficacy as well. This will be something we will discuss quite a bit as time goes on.”

The accelerated approval of sunvozertinib is based the multinational, open-label WU-KONG1B trial. The dose randomization trial evaluated the efficacy of the drug in 85 patients with locally advanced or metastatic NSCLC who had EGFR exon 20 insertion mutations and experienced disease progression during or after platinum-based chemotherapy.

“In that population, the response rate was robust, 46%. Importantly, these responses were durable, just north of 11 months for the median,” Dr. Liu said. “Side effects from this oral therapy include diarrhea. We can also see mucositis, other EGFR wild-type–related toxicity, CPK elevation, more of a paper toxicity, but it’s a pretty well-tolerated drug.”

Dr. Liu explained how the accelerated approval of sunvozertinib will shape the treatment landscape for patients with NSCLC who harbor EGFR mutations.

“This now gives us another option beyond amivantamab, the EGFR-MET bispecific antibody. Of course, that is our standard of care in the frontline setting—combined with chemotherapy—based on the PAPILLON study," he said. "While the approval of amivantamab is in the frontline setting and sunvozertinib is in the second line and beyond, certainly, some will compare these two agents …  Over the next few years, we'll be doing a rank-and-file [evaluation], trying to identify where we should use these drugs and in what setting.”

This will have implications for treatment sequencing, Dr. Liu said, because the oral administration route of sunvozertinib makes its use as an adjuvant therapy and a consolidation therapy “a little bit more appealing,” but there are questions about resistance and optimal sequencing.

“We don't know how well amivantamab works after this agent. We do know that this agent does retain activity after amivantamab,” Dr. Liu said. “When we think of the optimal sequence, it really is going to depend on resistance—not just toxicity—and patient preference. Those will certainly weigh in heavily. We really want to know about resistance when we're crafting an optimal sequence. And how does prior therapy affect the efficacy of these drugs in later-line settings?”

Beyond sunvozertinib and amivantamab, there are also many additional drugs that are under investigation in this space, Dr. Liu said.

“For now though, we have amivantamab approved in the frontline setting with chemotherapy, and then at the time of progression, sunvozertinib is a very appealing option in that second-line setting,: he said. "Other trials will seek to explore further roles for this drug for EGFR exon 20 insertion non–small cell lung cancer.”

He concluded by reflecting on the biology of EGFR exon 20 insertions and what the future may hold for targeting and treating them.

“When we think of exon 20 insertions, it's not one alteration. It really is a large family of mutations with some very important differences biologically,” Dr. Liu said. “In the future we will be able to personalize this further where specific drugs will be used in specific settings.”

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