Takeda earns win for its TKI inhibitor in tiny lung cancer group — but GI side effects could be an early red flag
Japanese drugmaker Takeda has made a big push in recent years to build a hand in oncology, particularly in the next-gen cancer space. One of those candidates, tyrosine kinase inhibitor (TKI) mobocertinib, recently earned the FDA’s interest in a small section of untreated lung cancer patients, but will severe GI side effects be a roadblock?
Takeda’s oral mobocertinib posted clinically significant objective response rates in a Phase I/II adaptive trial drugging metastatic non-small cell lung cancer patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, according to data presented Thursday at the virtual World Conference on Lung Cancer.
Patients receiving mobocertinib hit an ORR of 35% as judged by the trial’s investigators and 28% from an independent data review committee. The drug also showed a median duration of response of 17.5 months — both investigators and the DRC agreed on that figure — and progression-free survival of 7.3 months.
According to Chris Arendt, Takeda’s head of oncology, the pooled results show promise for exon 20-positive patients, who make up about 10% of the total EGFR NSCLC population and have a particularly poor prognosis. Despite the single-figure gap between investigators’ and the committee’s findings, Arendt told Endpoints News his team didn’t view the difference as meaningful given “a bit of a wobble” in terms of judging response.
It’s a small population but one with a high unmet clinical need. Mobocertinib earned the FDA’s breakthrough designation tag back in April for second-line use after platinum-based chemo and is looking to bring the drug into the first-line use in further trials.
But it wasn’t all roses for Takeda’s drug. Investigators noted a high rate of severe diarrhea in trial patients — enough so that they instituted a diarrhea management protocol for patients in the Phase I portion of the trial and continued in the Phase II expansion. In all, diarrhea was reported in 90% of all patients with severe side effects, followed by rash at 45%. Nineteen percent of the study’s 114 patients dropped out, with diarrhea and nausea tagged as the most common cause.
Seeing those GI side effects early, Takeda’s investigators instituted a diarrhea protocol that Arendt declined to outline. He said the drugmaker would use those guidelines in future trials and would likely file for regulatory approval to include the protocol on mobocertinib’s potential label. Even with the guidelines in place, the vast majority of patients with severe side effects reported diarrhea, likely indicating an even higher rate of diarrhea in patients who didn’t receive the protocol.
When asked to clarify the rate of diarrhea in patients prior to those guidelines being put in place, Arendt “caution(ed) a little bit in terms of over-interpreting” and said the protocol was designed to be “available to patients and not onerous.” The drugmaker plans to present further details on those guidelines at a later date, Arendt said, and noted that severe diarrhea was common in exon 20-positive patients after chemo.
With Phase II data in hand, Takeda is working on filing mobocertinib’s application with the FDA for second-line use and is also gunning for earlier use in exon 20-positive patients, Arendt said. The drugmaker is looking to confirm its Phase II findings on the global level and has earned a breakthrough tag in China to speed development there.