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.

Mark Wild­gust

“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.

Math­ai Mam­men

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.”

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

FDA announced today that doctors and pharmacists can now prescribe Paxlovid to patients without a positive test for Covid-19.

CDER Director Patrizia Cavazzoni reissued Paxlovid’s authorization letter Wednesday, saying it has revised the authorization to “no longer require positive results of direct SARS-CoV-2 viral testing.” The EUA now requires instead that adults and kids 12 years of age and older have a “current diagnosis of mild-to-moderate COVID-19.”