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P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)
- Event: WCLC 2018
- Type: Poster Viewing in the Exhibit Hall
- Presentations: 1
- Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
P1.13-44 - Safety, PK, and Preliminary Antitumor Activity of the Oral EGFR/HER2 Exon 20 Inhibitor TAK-788 in NSCLC (ID 12373)
16:45 - 18:00 | Author(s): Jian Zhu
TAK-788 (AP32788) is an investigational tyrosine kinase inhibitor (TKI) with potent, selective preclinical activity against activating EGFR and HER2 mutations, including exon 20 insertions. We report early results of a phase 1/2 first-in-human, open-label, multicenter study of TAK-788 (NCT02716116).a9ded1e5ce5d75814730bb4caaf49419 Method
Patients with advanced non-small cell lung cancer (NSCLC) refractory to standard therapy received daily oral doses (5–120 mg) of TAK-788 in the ongoing dose-escalation phase (3+3 design). Preliminary antitumor activity (by RECIST v1.1), safety, and PK are reported for patients who received ≥1 dose.4c3880bb027f159e801041b1021e88e8 Result
As of 8-Sep-2017, 34 patients (median age, 60 y; female, 65%; ≥2 prior anticancer therapies, 88%; Table) were treated with TAK-788; 10 remain on treatment at data cutoff. AUC0‑24,ss increased in a dose-proportional manner over the dose range evaluated; the effective t1/2 was ~16 (range 6–28) h. The most common treatment-emergent AEs (TEAEs; ≥20%) were diarrhea (47%), nausea (26%), and fatigue (21%). Grade ≥3 TEAEs in ≥2 patients (excluding disease progression) were dyspnea (n=3, 9%) and anemia, asthenia, dehydration, lung infection, pleural effusion, pneumonia, and pneumonitis (n=2 each, 6%). Two DLTs, both pneumonitis, were reported (80 mg, grade 3; 120 mg, grade 5). Of 14 evaluable patients, 3 had PR (80 mg, n=2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n=3; 80 mg, n=2; 120 mg, n=1), and 5 had PD as best response (40 mg, n=3; 80 mg, n=1; 120 mg, n=1). All patients with PR had EGFR exon 20 insertions.8eea62084ca7e541d918e823422bd82e Conclusion
TAK-788 exhibits antitumor activity in patients with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs. Phase 2 will begin after determination of the RP2D, with 4 molecularly defined cohorts in NSCLC. Updated data will be presented, including the recommended phase 2 dose (RP2D).
Mutation type,a %
Common EGFR mutations (exon 19 deletion / L8585R) 25 20 0 0 0 0 6 EGFR-T790M+ 0 0 0 0 14 0 3 EGFR exon 20 insertion 50 40 60 83 71 57 62 HER2 0 20 40 17 14 29 21 a One patient (20 mg) had both EGFR and HER2 mutations; 1 patient (80 mg) had EGFR exon 20 insertion + T790M.
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