Abstract 2211
Background
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. We conducted a phase II trial of pembrolizumab with chemotherapy/trastuzumab.
Methods
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. 22 pts received 1 cycle of induction P/T prior to initiation of chemotherapy. The primary endpoint was 6-months PFS; with target accrual of 37 pts. Secondary endpoints included safety, OS, ORR, and biomarker analysis.
Results
Accrual completed and 100% of the 37 evaluable pts had tumour regression (ranging from -4% to -100%). 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. Median PFS was 14.2 months (mo), with 70% 6 mo PFS. Median follow up was only 8 mo. In pts with available material, 14/36 (40%) had PD-L1 CPS >1 and median TMB was 4.4 mut/Mb (0-10.6). There was no correlation between PD-L1 status and PFS or OS. 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. CtDNA decreased in 16/24 tested pts after 1 cycle of induction T/P alone. irAEs included interstitial nephritis Gr4 (3%), transaminitis Gr3 (11%), Gr4 (3%), colitis Gr3 (3%).
Conclusions
40% remain on therapy, and so the primary endpoint should be reached by 9/19. Updated survival, correlative studies and will be presented. These promising preliminary safety and efficacy results led to initiation of a definitive phase III Keynote 811 trial (NCT03615326).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Memorial Sloan Kettering Cancer Center.
Funding
Merck.
Disclosure
Y.Y. 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. S. 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. G.Y. 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. D.H. 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. D. 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. J.F. Hechtman: Research grant / Funding (institution): Bayer; Honoraria (institution): Medscape; Advisory / Consultancy: Axiom Healthcare Strategies; Advisory / Consultancy: Cor2Ed. M. Lamendola-Essel: Advisory / Consultancy: Rockefeller University. All other authors have declared no conflicts of interest.
Resources from the same session
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract
4581 - Timing to achieve complete response (CR) after definitive chemoradiotherapy (ChRT) in patients with squamous cell carcinoma of the anal (SCCAC) with and without HIV infection: a multicenter retrospective study
Presenter: Marcos Camandaroba
Session: Poster Display session 2
Resources:
Abstract
1712 - Planned organ preservation for T2 T3 M0 rectal adenocarcinoma. A possible option using chemoradiotherapy (CRT) and Contact X-ray Brachytherapy (CXB). A French multicenter study.
Presenter: Jean-Pierre Gérard
Session: Poster Display session 2
Resources:
Abstract
4639 - A Phase 1b Study of E7046 (AN0025) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Rectal Cancer
Presenter: Lucjan Wyrwicz
Session: Poster Display session 2
Resources:
Abstract
2310 - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: a propensity score analysis
Presenter: Ahrong Ham
Session: Poster Display session 2
Resources:
Abstract
2747 - Neoadjuvant chemoradiotherapy with/without lateral lymph node dissection for low rectal cancer: Which patients can benefit?
Presenter: Daisuke Nishizaki
Session: Poster Display session 2
Resources:
Abstract
2877 - The impact of completeness of chemotherapy on the efficacy of irinotecan in the preoperative chemoradiotherapy of locally advanced rectal cancer.
Presenter: Jingwen Wang
Session: Poster Display session 2
Resources:
Abstract
3050 - Feasibility of robot-assisted surgery in elderly patients with rectal cancer
Presenter: Wei-Chih Su
Session: Poster Display session 2
Resources:
Abstract
4109 - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: a case-control non-inferiority trial
Presenter: Valerii Ivanov
Session: Poster Display session 2
Resources:
Abstract
4813 - Differential of the nutritional index before and after neoadjuvant chemoradiotherapy as a prognostic factor of recurrence in patients with locally advanced adenocarcinoma of the rectum
Presenter: Leslie Navia-Ortuño
Session: Poster Display session 2
Resources:
Abstract