#KEYNOTE 811 TRIAL#

All other authors have declared no conflicts of interest.Clarivate oncology experts analyzed more than 2,400 ASCO abstracts and selected the top 10 based on their expected impact on the drug treatment landscape. Lamendola-Essel: Advisory / Consultancy: Rockefeller University. Hechtman: Research grant / Funding (institution): Bayer Honoraria (institution): Medscape Advisory / Consultancy: Axiom Healthcare Strategies Advisory / Consultancy: Cor2Ed. Solit: Advisory / Consultancy: Pfizer Advisory / Consultancy, Shareholder / Stockholder / Stock options: Loxo Oncology Advisory / Consultancy: Illumina Advisory / Consultancy: Vivideon Therapeutics Honoraria (institution), Speaker Bureau / Expert testimony: Lilly Oncology. Ilson: Advisory / Consultancy: Merck Advisory / Consultancy: Astellas Advisory / Consultancy: Bayer Advisory / Consultancy: Pieris Advisory / Consultancy: Roche Advisory / Consultancy: AstraZeneca Advisory / Consultancy: Eli Lilly Advisory / Consultancy: Britsol Myers Squibb Advisory / Consultancy, Contracted Research: Taiho. Ku: Advisory / Consultancy, Research Support: Arog Advisory / Consultancy, Research Support: Bristol-Myers Squibb Advisory / Consultancy: Eli Lilly Advisory / Consultancy, Research Support: Merck Advisory / Consultancy, Research Support: Pieris Advisory / Consultancy, Research Support: Zymeworks. Maron: Non-remunerated activity/ies, Research Collaboration Only: Guardant Health Shareholder / Stockholder / Stock options: Calithera Travel / Accommodation / Expenses: Merck Licensing / Royalties, Non-remunerated activity/ies, Research Collaboration Only: Genentech. Janjigian: Advisory / Consultancy, Research grant / Funding (self): Bristol-Meyers Advisory / Consultancy, Research grant / Funding (self): Eli Lily Advisory / Consultancy: Daiichi Sankyo Advisory / Consultancy: Pfizer Advisory / Consultancy, Research grant / Funding (self): Merck Research grant / Funding (self): Amgen Advisory / Consultancy, Research grant / Funding (self): Bayer Research grant / Funding (self): Boehringer Ingelhiem Research grant / Funding (self): Genentech/Roche Advisory / Consultancy: Merck Serono Advisory / Consultancy: Imugene.

#KEYNOTE 811 TRIAL#

Clinical trial identification Editorial acknowledgement Legal entity responsible for the study

These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial (NCT03615326). Updated survival, correlative studies and will be presented. ConclusionsĤ0% remain on therapy, and so the primary endpoint should be reached by 9/19. irAEs included interstitial nephritis Gr4 (3%), transaminitis Gr3 (11%), Gr4 (3%), colitis Gr3 (3%). CtDNA decreased in 16/24 tested pts after 1 cycle of induction T/P alone. ERBB2 amplification was evident by tissue-NGS in 17/30 (63%) and ctDNA-NGS in 17/30 (58%) pre-treatment, while the remaining pts were ERBB2- by NGS likely due to tumour heterogeneity or low tumour content. There was no correlation between PD-L1 status and PFS or OS. In pts with available material, 14/36 (40%) had PD-L1 CPS >1 and median TMB was 4.4 mut/Mb (0-10.6).

Median PFS was 14.2 months (mo), with 70% 6 mo PFS. The RECIST 1.1 ORR was 81% (27 PR, 3 CRs), and 12 (52%) of pts that received induction P/T x 1 cycle showed reduction in target lesions. ResultsĪccrual completed and 100% of the 37 evaluable pts had tumour regression (ranging from -4% to -100%). Secondary endpoints included safety, OS, ORR, and biomarker analysis. The primary endpoint was 6-months PFS with target accrual of 37 pts. 22 pts received 1 cycle of induction P/T prior to initiation of chemotherapy. Patients (pts) with previously untreated HER2 IHC 3+ or FISH+ tumours irrespective of PD-L1 status received intravenous P 200 mg flat dose, T 6 mg/kg (after 8 mg/kg load), O 130 mg/m2 every 3 weeks and oral C 850 mg/m2 2 weeks on/1 week off. We conducted a phase II trial of pembrolizumab with chemotherapy/trastuzumab.

Trastuzumab stimulates HER2-specific T cell responses and increases tumour PD-L1 expression, and anti-PD-1 antibody can help enhance T cell-specific immunity of trastuzumab.