RE: Comparing TAK-788 and Pozi’s most recent data. IASLC TAK-788 data didn’t change vs ASCO 2019 as far as I could tell. I was under the impression you can’t present the same data at another conference; the only change I noticed is the way it's presented. Here's the abstract
P1.01-127 - Antitumor Activity of the Oral EGFR/HER2 Inhibitor TAK-788 in NSCLC with EGFR Exon 20 Insertions 09:45 - 09:45 | Presenting Author(s): Gregory J Riely | Author(s): Joel W Neal, D. Ross Camidge, Alexander Spira, Zosia Piotrowska, Leora Horn, Daniel B Costa, Anne Tsao, Jyoti D Patel, Shirish Gadgeel, Lyudmila Bazhenova, Viola W. Zhu, Howard West, Sylvie Vincent, Jian Zhu, Shu Jin, Steven Zhang, Shuanglian Li, Pasi A Jänne ? Abstract Background We report results of a phase 1/2 open-label, multicenter study of TAK-788 (NCT02716116), an oral investigational EGFR/HER2 inhibitor. Method Patients with advanced, previously treated NSCLC received daily TAK-788 in dose escalation and expansion cohorts based on tumor genotype. Antitumor activity was determined for patients with EGFR exon 20 insertions who received TAK-788 160 mg QD. Safety is reported for all patients across all doses and at 160 mg. To improve gastrointestinal tolerability, food intake instructions in this ongoing study were amended to allow for administration with or without a low-fat meal based on emerging clinical pharmacokinetic data in a healthy volunteer study (data on file). Result As of 14 Sep 2018, 101 patients (median age, 61 y; female, 70%; ≥2 prior anticancer therapies, 76%; brain metastases, 53%) were treated with TAK-788 at 5–180 mg QD. RP2D was determined to be 160 mg QD. 28 patients with EGFR exon 20 insertions were treated with 160 mg QD during dose escalation or in expansion cohort 1 (3.6 months on treatment; 3.8 treatment cycles [medians]); 24 patients remain on treatment. At data cutoff, best response (RECIST v1.1) among 26 patients with ≥1 disease assessment was PR, n=14; SD, n=9; and PD, n=1 (objective response rate, 54%; 95% CI: 33.4%–73.4%); 2 patients were unevaluable. 7/14 objective responses (all PR) were confirmed (6 awaiting confirmation; 1 unconfirmed PR at 160 mg QD); median time to response in these 14 patients was 56 days. 23/26 patients (89%; 95% CI: 69.9%–97.6%) achieved disease control. 23/24 evaluable patients with EGFR exon 20 insertions treated at 160 mg QD had decreased target lesion measurements (median best percent change, -32.6% [-79.1%–3.8%]). Most common TEAEs (≥20%) in patients treated with 160 mg QD: diarrhea (85%), rash (43%), nausea (41%), vomiting (30%), decreased appetite (28%), stomatitis (22%); grade ≥3 TEAEs (≥5%): diarrhea (26%); hypokalemia, nausea, stomatitis (7% each). Among patients treated with 160 mg QD, median dose intensity was 93%, rate of dose reduction due to AEs was 21.7%, and rate of treatment discontinuation due to AEs was 10.9%. There was no clear trend that response to TAK-788 was enriched in any single EGFR exon 20 insertion variant. Conclusion In NSCLC patients with EGFR exon 20 insertions, TAK-788 demonstrated antitumor activity and a safety profile consistent with other EGFR TKIs.
Anyhows, what I stated back in May comparing it to pozi still stands
In looking at the TAK-788 ASCO data and comparing it to pozi MDACC WCLC 2018 data, several things stick out. - TAK data set had 24 patients, MDACC pozi had 44 patients - TAK data is still maturing and currently has an unconfirmed RR of 54% (14/26); posi’s unconfirmed RR was 55% - TAK at this point in time has a confirmed RR of 27% (7/26; could land anywhere from 27 to 54%) whereas posi’s is 43% - Don’t know when TAK-788 did the confirmatory scan for responses. I assume for TAK-788 it was at 4 weeks; for the MDACC trial it was at 8 weeks. For Spectrum’s Zenith20 trial the confirmatory scan will be at 4 weeks. - Only able to compare several AEs that they both list (TAK-788 vs pozi); diarrhea (85% vs 69.8), rash (43% vs 55.6), nausea (41% vs 23.6), vomiting (30% vs 20.6)
So the last bullet compares the AEs from the TAK-788 trial to pozi's MDACC trial for the AEs they both list. And looking at that, I still don't get why they say TAK-788 is less toxic than pozi.
