Abstract 5294
Background
Checkpoint inhibitors (CPIs) have transformed treatment of many malignancies. However, to date, response to checkpoint blockade in unselected gastrointestinal (GI) cancers has been disappointing. Tumours which display a non-T-cell inflamed phenotype such as mismatch repair proficient (MMRp) oesophagogastric (OG) and colorectal cancers (CRC) respond less frequently to CPIs. Changes in tumour expression of antigens and increased immune infiltrate are associated with improved response to CPIs. Epigenetic modulation of tumours using HDAC inhibitors can lead to increased tumour antigen presentation, immune cell infiltrates and thereby may increase the chance of response to immunotherapy.
Trial design
EMERGE is designed to evaluate the safety and efficacy of domatinostat, a selective class 1 histone deacetylase inhibitor in combination with avelumab, an anti-PD-L1 monoclonal antibody in patients with previously treated, inoperable or metastatic MMRp OG and CRC. The trial is conducted in 2 stages: Phase IIA will establish a safe and tolerated dose of domatinostat plus avelumab using a 3 + 3 dose finding design and escalating doses of domatinostat will be examined, dosing of avelumab will remain constant. The phase IIB will use a Simon two stage optimal design to assess efficacy of the combination in achieving radiological response according to RECIST v1.1. The primary endpoint of the phase IIB is best objective response rate (ORR) at 6 months. To rule out an ORR of 5% in the CRC cohort, while aiming for 20%, 1/10 and 4/29 responses are required in the 1st and 2nd stages respectively. To rule out an ORR of 15% in the OG cohort while aiming for 35%, 2/9 and 9/34 responses are required in the 1st and 2nd stages respectively with a 1-sided alpha of 5% and 80% power. Secondary endpoints are DoOR, PFS, OS, DCR, safety and tolerability. Exploratory objectives will investigate dynamic changes in expression of tumour associated antigens and immune infiltrates in baseline and on-treatment biopsies and correlate baseline tumour characteristics and circulating biomarkers with tumour response and survival. Recruitment commenced in January 2019, 83 patients will be recruited over 3 years. (ClinTrials.gov. ID: NCT03812796).
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Royal Marsden Hospital NHS Foundation Trust.
Funding
Royal Marsden Hospital NHS Foundation Trust, 4SC.
Disclosure
M. Hubank: Research grant / Funding (self), Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (self), Research grant / Funding (institution): Roche Diagnostics; Research grant / Funding (self), Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (self), Research grant / Funding (institution): Guardant Health; Research grant / Funding (self), Research grant / Funding (institution): Celgene; Research grant / Funding (self), Research grant / Funding (institution): Eli Lilley. I. Chau: Honoraria (self): Eli-Lilly; Research grant / Funding (institution): Eli-Lilly; Research grant / Funding (institution): Janssen-Cilag; Research grant / Funding (institution): Sanofi Oncology; Research grant / Funding (institution): Merck-Serono; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Bristol Meyers Squibb; Advisory / Consultancy: MSD; Advisory / Consultancy: Bayer; Advisory / Consultancy: Roche; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy: Five Prime Therapeutics; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Oncologie International; Advisory / Consultancy: Pierre Fabre. N. Starling: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Eli Lilly; Travel / Accommodation / Expenses: Merck; Travel / Accommodation / Expenses: Roche; Honoraria (self): AstraZeneca; Honoraria (self): Eli Lilly; Honoraria (self): Merck; Honoraria (self): Servier; Advisory / Consultancy: Pfizer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Servier. D. Cunningham: Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): 4SC; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): Merck. All other authors have declared no conflicts of interest.
Resources from the same session
3608 - Prognostic impact of Body Mass Index (BMI) on overall survival in patients with metastatic breast cancer
Presenter: Khalil SALEH
Session: Poster Display session 2
Resources:
Abstract
2686 - Clinicopathological characteristics, survival and prognostic factors of breast cancer-related microangiopathic haemolytic anemia: a multicenter study
Presenter: Marion Alhenc Gelas
Session: Poster Display session 2
Resources:
Abstract
1565 - Metabolic tumor volume by 18F-FDG PET/CT is an independent prognostic factor in metastatic breast cancer
Presenter: Heekyung Ahn
Session: Poster Display session 2
Resources:
Abstract
4498 - Patient Preferences for breast cancer treatments: A Discrete Choice Experiment from four European countries
Presenter: Thomais Konstantopoulou
Session: Poster Display session 2
Resources:
Abstract
1423 - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase 2 study
Presenter: Diana Lüftner
Session: Poster Display session 2
Resources:
Abstract
2284 - Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype
Presenter: Hee Kyung Kim
Session: Poster Display session 2
Resources:
Abstract
4598 - Administration of chemotherapy for metastatic breast cancer near the end of life: a population registry study
Presenter: Luisa Edman Kessler
Session: Poster Display session 2
Resources:
Abstract
5706 - Prognostic value of histological growth pattern in patients operated for breast cancer liver metastases
Presenter: Ali Bohlok
Session: Poster Display session 2
Resources:
Abstract
1697 - Illness perceptions, quality of life and mood in metastatic breast cancer patients
Presenter: Isabel Domingues
Session: Poster Display session 2
Resources:
Abstract
1935 - Multidisciplinary Treatments Increases Overall Survival in Patients with Newly Diagnosed Stage IV Breast Cancer:An Analysis of 2010–2014 SEER Data
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract