Ben Creelan, MD

Ben Creelan, MD, Associate Member of Moffitt Cancer Center, Tampa, Florida, provided some context for the CHRYSALIS study. “This dual bispecific antibody targeting both EGFR and MET clearly has potent single-agent activity in patients with MET exon 14 skipping NSCLC,” he said.

“For now, it is not preferred as first-line therapy because of the dosing requirement and side-­effect profile. Administration requires infusions every week for the first month and then every 2 weeks after that. Most patients would prefer to take a pill,” Dr.Creelan continued.

“Right now, we have three oral tyrosine kinase pills that work well in treatment-naive patients: capmatinib, tepotinib, and crizotinib. The activity of amivantamab looks comparable to those drugs in treatment-naive patients. However, amivantamab caused rash in 80%, and initial infusion reactions are common. Other adverse events can include low albumin and pneumonitis. Overall, amivantamab is just more unwieldly for me to manage as a medical oncologist. Managing the side effects and infusion frequency of amivantimab is not trivial. Instead, with the three commercially available pills, then the patient just has a visit every 3 months,” he said.

Study Implications

“At present, amivantimab has the most merit for previously treated patients who need to be treated for progressive disease. It clearly has a role in ­NSCLC with EGFR exon 20 insertions, as well as for patients with disease progression on traditional EGFR-targeted tyrosine kinase inhibitors,” Dr. Creelan commented.

“Now this abstract shows that the drug has activity in both treatment-naive and previously treated MET exon 14 NSCLC. Furthermore, amivantamab has a different mechanism of action than other MET inhibitors, and it is already commercially available, so if patients have disease progression while on a prior MET tyrosine kinase inhibitor, it may be worth pursuing off-label in select settings,” he continued.

“However, before amivantamab can be considered standard of care or truly practice-changing, studies are needed in a larger cohort of patients with MET exon 14 skipping mutations, including patients who have had disease progression immediately following a prior MET inhibitor [ie, within 30 days],” he concluded. 

DISCLOSURE: Dr. Creelan has served as a consultant or advisor to AbbVie, Boehringer Ingelheim, and Celgene; has served on a speakers bureau for Ariad, AstraZeneca/MedImmune, Bristol Myers Squibb, Genentech/Roche, and Takeda; has received institutional research funding from Boehringer Ingelheim, Bristol Myers Squibb, Iovance Biotherapeutics, and Prometheus; and has been reimbursed for travel, accommodations, or other expenses from AstraZeneca.