Tucatinib Receives FDA Approval

Little tucatinib is all grown up! The TKI that started out at Array long, long ago has now been FDA approved in combination with Herceptin and Xeloda for the treatment of 2L+ HER2+ metastatic breast cancer. Additional international approvals could be imminent, as the submission was part of a concurrent review program between the FDA and worldwide regulatory authorities. This is fantastic news for everyone but the Kadcyla sales force, though Genentech will get a slice of the pie via some incremental Xeloda sales.

The approval was supported by data from the HER2CLIMB trial, which enrolled 612 subjects and randomized them 2:1 to tucatinib or placebo plus Herceptin and Xeloda. Subjects with brain mets at baseline comprised 47.5% of the study population. This is their story:

Among subjects with measurable disease at baseline, the confirmed objective response 40.6% in the tucatinib group and 22.8% in the placebo group. But look at those numbers! The brain mets patients didn’t do much worse than patients with visceral mets. Cascadian went in boldly by enrolling brain mets patients, and the gamble paid off. They have brain mets featured prominently in their labeling, and they’re an example for all the companies that have excluded brain mets patients from their trials for fear of muting response rates. But patients in the real world, in HER2+ breast cancer, have brain mets. I have brain mets. I’ve looked at a lot of eligibility criteria, and while we’ve seen brain mets exclusions gradually relax over the past decade, most trials that allow them still caution that they must be stable.

Cheers to you, Cascadian/SeaGen.

DS-8201 has a PDUFA Date

Yes! The date is F1Q:20, so I might be getting a prolonged OS for Christmas!

Daiichi announced today that they’ve been granted FDA Priority Review for their highly worthy DS-8201, which looked promising out of the gate and recently demonstrated a 59.5% response rate in HER2+ metastatic breast cancer patients who had previously been treated with T-DM1. Those results, from a 118-subject Phase 1, were published in June. The study also reported some total insanity, like a 20.7-month duration of response (DOR) and a 22.1-month PFS. It’s not comparable given the phases, designs and number of subjects enrolled in this phase 1 versus EMILIA, but T-DM1 had a phase III PFS of around 9-10 months, so DS-8201 is likely to displace that agent as the second-line treatment of choice in this setting (first-line being taxane + Herceptin + Perjeta).

The data above are old news, but the press release says the submission package also includes pivotal phase 2 DESTINY-Breast01 data, which “validated” the phase 1 results and which no one has seen yet, though they note that it will be presented at San Antonio. DESTINY 1 looks at a similar population (T-DM1 pre-treated MBC), but its 230 subjects were randomized to varying dose levels. Primary endpoint is ORR, so it would be shocking if this result isn’t pretty compelling, considering what we’ve seen so far.

Like T-DM1, DS-8201 is an ADC where Herceptin is conjugated to a chemo agent; in DS-8201’s case, it’s a TOP-I inhibitor, similar to irinotecan.

The Puma Panel

I didn’t think neratinib was getting through. As much as I want more flexibility in prescribing and a more moderate drug approval pathway, why does it have to be neratinib?

Despite very modest clinical benefit, a lot of toxicity and a broad label, this morning’s FDA panel voted 12-4 in favor of more options for cancer patients. The panelists did seem to take patient selection seriously, though it’s unclear how that will pan out when Puma is loose in the market. What I’m curious about is whether patients will demand it, whether the patient representatives Puma paid to speak – the what-if-Mommy-dies, I-want-to-do-everything-to-fight-this types – are representative of the overall population. Continue reading “The Puma Panel” →