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Early results from TAK-788 in NSCLC with EGFR exon 20 insertions

Presented by
Dr Gregory Riely, Memorial Sloan Kettering Cancer Centre, USA
ASCO 2019
Medical writer: Muriel Cunningham

TAK-788 is an investigational oral EGFR/HER2 inhibitor under development for the treatment of non–small cell lung cancer (NSCLC) with EGFR/HER2 mutations, including patients with NSCLC EGFR exon 20 insertions. A phase I/II open-label study of TAK-788 enrolled patients with advanced, previously treated NSCLC from multiple centres (NCT02716116). In the phase I dose-escalation trial, TAK-788 doses ranged from 5 to 180 mg once a day (QD), with a recommended phase II dose (R2PD) of 160 mg QD. Results as of the data cut off (March 1, 2019) were presented by Gregory Riely, MD, PhD, of Memorial Sloan Kettering Cancer Centre during an Oral Abstract Session on June 3 (Abstract 9007).

Safety data were reported for the 137 patients who received any dose of TAK-788 and the subgroup of 72 patients treated with at least one dose of TAK-788 at 160 mg QD. Ninety-five percent of patients at any dose or at the R2PD dose experienced a treatment-emergent adverse event (TEAE). The rates of TEAEs grade 3 or higher were 61% overall and 63% for patients taking 160 mg QD. Approximately 50% of all patients and 50% of those taking 160 mg QD required a dose interruption due to TEAEs. Ten patients (14%) receiving 160 mg QD and 18 patients overall (13%) discontinued treatment due to TEAEs. The most frequently reported TEAEs at the 160 mg QD dose were diarrhea (85%), nausea (43%), rash (36%), vomiting (29%), and decreased appetite (25%).

Efficacy data were presented for the 28 patients with EGFR exon 20 insertions who received at least one dose of TAK-788 160 mg QD (six patients in dose escalation and 22 in expansion cohort 1). As of the data cut off, 14 of 28 patients (50%) remained in the study and the other 14 (50%) had discontinued (seven patients due to disease progression, three due to TEAEs, and three as a result of physician decision; one patient died). The prespecified eligibility criteria for efficacy included at least one prior regimen of systemic therapy (history of prior tyrosine kinase inhibitor [TKI] therapy allowed if no response) and excluded patients with active and measurable brain metastases. Efficacy data are provided in the Table. Lower response rates and shorter median progression-free survival were seen in the patients with baseline brain metastases. “TAK-788 demonstrates responses in patients with diverse EGFR exon 20 insertion variants. The TAK788 safety management profile was manageable and consistent with that of other EGFR TKIs,” Dr. Riely said.

Table: Efficacy results from patients with NSCLC EGFR Exon 20 insertions treated with ≥ 1 dose of TAK-788 160 mg QD

Abbreviations: CI, confidence interval, CNS, central nervous system; NSCLC, non-small cell lung cancer; NR, not reached; PFS, progression-free survival; QD, once a day.a Response by RECIST v1.1. Median time to response among confirmed responders was 1.8 months. At data cutoff, 12/15 responses were confirmed, with three partial responses unconfirmed at 160 mg QD.b Seven of 12 patients (58%) had active brain metastases at baseline.c Stable disease observed ≥ 6 weeks after first study drug administration.

“We enthusiastically look forward to additional data with this drug,” said Discussant Christine M. Lovly, MD, PhD, of Vanderbilt University, but she called attention to the rates of overall TEAEs and those grades 3 and higher. Dr. Lovly encouraged clinicians to expand the reach of precision medicine by improving the uptake and utilization of tumour biomarker testing.

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