J&J guns for quick drug OK in lung cancer niche, taking the first step challenging AstraZeneca in EGFR
J&J has leapt straight from a Phase I trial to a BLA for amivantamab, a bispecific antibody designed to treat a subset of metastatic non-small cell lung cancer patients by targeting EGFR and MET simultaneously.
While the first epidermal growth factor receptor inhibitors were approved more than a decade ago, this is the first drug targeting EGFR exon 20 insertion mutations to ever be filed with the FDA, the company said.
“When you think about EGFR-driven lung cancer, you have the common mutations, and then you have some of the rarer kinds,” Mark Wildgust, the VP of global medical affairs, oncology at J&J’s Janssen subsidiary, previously told Endpoints News. “And Exon20 insertion is one of them.”
The FDA granted a breakthrough therapy designation for this use, zeroing in on patients who progressed on or after platinum-based chemotherapy, in March.
The data undergirding the filing comes from the Phase I CHRYSALIS study, an open-label trial that enrolled multiple cohorts to test amivantamab as both monotherapy and in combination with lazertinib, a third-generation EGFR TKI. Among 39 evaluable patients, J&J reported at ASCO this year, the overall response rate for amivantamab alone was 36%.
Among the 14 responders, median duration of response was 10 months and median progression-free survival registered at 8.3 months.
Unlike the traditional TKIs or even lazertinib, amivantamab binds to EGFR extracellularly, allowing it to skirt the co-mutations within binding pockets that can render a drug ineffective. Blocking MET amplifications, on the other hand, promises to blunt the other resistance pathways.
J&J has bigger plans for the drug aside from the monotherapy application — which is, after all, limited to a genetically defined population.
It is putting the amivantamab/lazertinib combo head-to-head with AstraZeneca’s top-selling Tagrisso in the frontline setting for a Phase III trial. Then there is another trial involving patients who have taken both Tagrisso and chemotherapy but still progressed.
“Lung cancer remains the leading cause of cancer deaths worldwide,” Mathai Mammen, Janssen’s global head of R&D, said in a statement. “Given this significant unmet need, we at Johnson & Johnson are committed to improving outcomes for patients diagnosed with this complex, deadly disease.”