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
4947 - Pre-treatment serum 25-hydroxyvitamin D levels and survival in a Danish cohort of patients with pancreatic cancer
Presenter: Louise Rasmussen
Session: Poster Display session 2
Resources:
Abstract
5124 - STAR_PAC: Phase I clinical trial repurposing all trans retinoic acid (ATRA) as stromal targeting agent in a novel drug combination for pancreatic cancer.
Presenter: Hemant Kocher
Session: Poster Display session 2
Resources:
Abstract
5257 - Outcomes of First Line FOLFIRINOX (FFX) Versus Gemcitabine and Nab-Paclitaxel (GN) in Patients with Advanced Pancreatic Cancer: Multi-Institutional Canadian Sites Experience
Presenter: Neha Papneja
Session: Poster Display session 2
Resources:
Abstract
1166 - Effect of prior cancer on survival outcomes for patients with pancreatic adenocarcinoma
Presenter: Chaobin He
Session: Poster Display session 2
Resources:
Abstract
1169 - Association of combination of irreversible electroporation ablation and chemotherapy with outcomes of locally advanced pancreatic cancer: a large cohort study
Presenter: Chaobin He
Session: Poster Display session 2
Resources:
Abstract
1222 - Results from phase I study of the oncolytic viral immunotherapy agent Canerpaturev (C-REV) in combination with gemcitabine plus nab-paclitaxel as first-line treatment of unresectable pancreatic cancer
Presenter: Yusuke Hashimoto
Session: Poster Display session 2
Resources:
Abstract
1698 - Multicenter retrospective study of gemcitabine plus nab-paclitaxel for elderly patients with advanced pancreatic cancer
Presenter: Masato Ozaka
Session: Poster Display session 2
Resources:
Abstract
2424 - Irinotecan Combined with Oxaliplatin and S1 in Patients with Metastatic Pancreatic Adenocarcinoma
Presenter: Keke Nie
Session: Poster Display session 2
Resources:
Abstract
2885 - Cancer-associated thrombosis in patients with pancreatic cancer and its correlation with plasma tissue factor level: A Japanese prospective cohort study
Presenter: Satoshi Kobayashi
Session: Poster Display session 2
Resources:
Abstract
3702 - A Phase I/Ib, multi-center trial of ARQ-761 (Beta-Lapachone) with gemcitabine/nab-Paclitaxel in patients with advanced pancreatic cancer
Presenter: Muhammad Beg
Session: Poster Display session 2
Resources:
Abstract