Janssen presented additional positive data from its phase I study of its bispecific antibody amivantamab in metastatic or unresectable non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.
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Janssen presented additional positive data from its phase I study of its bispecific antibody amivantamab in metastatic or unresectable non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations. As the company awaits regulatory decision in the U.S. and Europe. On the basis of the study, the Johnson & Johnson company already filed a Biologics License Application to the U.S. Food and Drug Administration last month and a Marketing Authorization Application to the European Medicines Agency earlier in January.
The company presented the new data – which it characterized as showing “robust activity and durable responses” – at the International Association for the Study of Lung Cancer’s 2020 World Conference on Lung Cancer in Singapore. In the study, patients whose disease progressed while previously on platinum-based therapy received amivantamab at the maximum tolerated dose of 1050 mg (1400 mg in patients weighing 80 kg or more), as a monotherapy or in combination with lazertinib, an investigational tyrosine kinase inhibitor (TKI). Investigators reported an overall response rate of 40%, the primary endpoint. Of the 33 responders, 4 had complete responses to treatment.
Secondary endpoints included a median progression-free survival of 8.3 months and a median overall survival of 22.8 months. Of 114 patients receiving amivantamab monotherapy in the trial, 13% reduced dosage due to treatment-related adverse events, and 4% discontinued the antibody altogether. The results were consistent with initial data reported last May.
Amivantamab targets mutations and amplifications in MET, as well as mutations in the receptor tyrosine kinase EGFR that are frequently driving NSCLCs. Even after treatment with tyrosine kinase inhibitors, metastatic NSCLC patients with EGFR mutations have a five-year survival rate under 20%, and median survival for patients with EGFR exon 20 mutations in particular are lower still.
No targeted therapies are currently approved in NSCLC patients with EGFR exon 20 mutations, but several are in development. Last year both amivantamab and mobocertinib, a TKI in development by Takeda, received breakthrough designations from FDA in the indication.
But the field has seen multiple recent disappoints. Last month, FDA approved AstraZeneca’s Tagrisso as an adjuvant therapy following tumor resection in NSCLC patients with EGFR exon 19 deletions or exon 21 L858R mutations, and it is also indicated as a first-line treatment for those patients, but data published last year casted doubt on its effectiveness for patients with exon 20 mutations. Also in December, Spectrum Pharmaceuticals reported results of a NSCLC trial showing its TKI poziotinib did not meet its primary endpoint in patients with EGFR exon 20 insertion mutations.
Brian Kenney, a Janssen spokesperson, says the company will continue testing a combination of amivantamab and Lazertinib, including in an ongoing phase III trial against osimertinib in untreated advanced EGFR-mutated NSCLC.
