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
5205 - Immune status of patients with different stages of colorectal cancer with and without circulating tumor cells
Presenter: Anastasia Sitkovskaya
Session: Poster Display session 2
Resources:
Abstract
5658 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Early Diagnosis of Colorectal Cancer
Presenter: Tianyu Liu
Session: Poster Display session 2
Resources:
Abstract
5779 - Detection of 5-hydroxymethylcytosine in Circulating-Free DNA for Prediction of The Efficacy of Conversion Therapy for Colorectal Cancer Liver Metastases
Presenter: Wenju Chang
Session: Poster Display session 2
Resources:
Abstract
4672 - mCRC gene profiling using the Idylla platform
Presenter: Christopher Bricogne
Session: Poster Display session 2
Resources:
Abstract
3393 - PIK3CA mutation in metastatic colorectal cancer (mCRC): association with clinico-pathological features and outcome
Presenter: Valentina Fanotto
Session: Poster Display session 2
Resources:
Abstract
1317 - Patient-Derived Xenografts (PDX) Identifies JMJD6 Inhibitor as an Effective Therapeutic Medicine in Colorectal Cancer.
Presenter: Feng Ye
Session: Poster Display session 2
Resources:
Abstract
1228 - DACH1 induced stemness of intestinal organoids by directly suppressing BMP signaling and contributes to intestinal tumorigenesis
Presenter: Xiang Hu
Session: Poster Display session 2
Resources:
Abstract
1147 - miR-148a inhibits early relapsed colorectal cancers and the secretion of VEGF by indirectly targeting HIF-1α under non-hypoxia/hypoxia conditions
Presenter: Hsiang-lin Tsai
Session: Poster Display session 2
Resources:
Abstract
1158 - Long noncoding RNA CASC21 promotes cell proliferation and metastasis in colon cancer.
Presenter: Qun Zhang
Session: Poster Display session 2
Resources:
Abstract
1259 - Prognostic and Predictive Impact On FMS-like Tyrosine Kinase 3 (FLT3) Amplification In Patients With Metastatic Colorectal Cancer
Presenter: Hiroko Hasegawa
Session: Poster Display session 2
Resources:
Abstract