medwireNews: The EGFR and HER2 inhibitor TAK-788 has antitumor activity against non-small-cell lung cancer (NSCLC) with EGFR exon 20 insertions, according to phase I/II findings reported at the 2019 ASCO Annual Meeting.
EGFR exon 20 insertions are seen in around 6% of EGFR-mutated NSCLC tumors and there are no approved targeted treatments for this population, presenter Gregory Riely (Memorial Sloan Kettering Cancer Center, New York, USA) told the audience in Chicago, Illinois, USA.
Indeed, he said: “Currently approved EGFR TKIs [tyrosine kinase inhibitors] have shown efficacy in NSCLC patients with common activating EGFR mutations, but are largely ineffective in patients with EGFR exon 20 insertions, with poor response rates and median PFS [progression-free survival] of approximately 2 months.”
In comparison, this study saw a confirmed objective response in 43% of 28 patients treated with second- or later-line TAK-788 at the recommended phase II dose of 160 mg once-daily, with disease control in 86%. Median PFS was 7.3 months.
TAK-788 appeared to be active against NSCLC with a range of exon 20 insertion variants, including the V769_D770insASV and H773_V774insNPH variants. However, responses did vary according to the presence or absence of baseline central nervous system metastases, with a confirmed objective response rate of 25% among the 12 participants with metastases and 56% for the 16 patients without, and median PFS of 3.7 and 8.1 months, respectively.
At the time of analysis, participants had been on treatment for a median of 7.9 months (range, 0.7 to ≥15.9 months) and 50% remained on study.
Riely described the adverse event (AE) profile of TAK-788 as “manageable and consistent with that of other EGFR TKIs.” He noted that among 137 patients treated at any TAK-788 dose in the multicohort study, “most treatment-related AEs were grade 1–2 and reversible,” while grade 3 treatment-related AEs – mostly diarrhea (12%) – were seen in 32% of patients.
Based on emerging data in healthy participants that indicate an effect of a low-fat meal on the pharmacokinetics of the agent, future studies will use updated food instructions in an effort to improve gastrointestinal tolerability, the presenter said.
TAK-788 will now be investigated globally in the EXCLAIM extension cohort, said Riely, in which the activity of TAK-788, along with survival and quality of life, will be assessed in 91 previously treated patients with locally advanced or metastatic NSCLC carrying EGFR exon 20 insertions.
By Catherine Booth
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2019 ASCO Annual Meeting; Chicago, Illinois, USA: 31 May–4 June