Abstract 2732
Background
New approaches are needed for patients with advanced endometrial cancer (EC) since there is no standard second-line therapy after failure to platinum-based chemotherapy. The TCGA subtypes, POLE and MSI, show high tumour mutation burden (TMB) that correlates with PD-L1 expression. Pembrolizumab (anti-PD-1 antibody) conferred a 13% objective response rate (ORR) in patients with advanced EC whose tumors expressed PD-L1. However, the majority of patients with advanced disease belong to the serous-like or CN-low subtypes, with fewer potential neoantigens and may experience less benefit from immunotherapy. We hypothesize that combining pembrolizumab with an inducer of immunogenic cell death such as doxorubicin could improve clinical responses in all EC subtypes. The purpose of this trial is to determine the efficacy/safety of the combination and to identify predictive biomarkers of response.
Trial design
This investigator-initiated, single-arm, multicenter, phase 2 study aims to enroll 41 to 51 patients with relapsed/metastatic EC (endometrioid, serous, squamous, clear-cell, and an exploratory cohort of carcinosarcoma). Patients must have received one prior line of platinum-based chemotherapy, have an ECOG PS ≤ 1, and tumor specimen available for biomarker analysis. Patients will receive IV doxorubicin (60 mg/m2) plus IV pembrolizumab (200 mg) every 3 weeks up to 9 cycles; treatment with pembrolizumab will continue in 3-week cycles until disease progression, unacceptable toxicity, or 35 administrations (approximately 2 years). The primary endpoint is investigator assessed progression-free survival (PFS) rate by RECIST v1.1 at 6 months. Key secondary endpoints include duration of response, PFS, ORR, overall survival, and the association with TCGA subtypes. An exploratory translational analysis will be also performed on tumour samples to investigate genetic predictors of response, such as distribution of PD-L1, tumour-stroma immune-regulatory gene expression, and TMB.The study is actively recruiting. At the time of submission, the safety run-in part with 6 patients had been completed with no safety concerns and 30 patients enrolled. Clinical trial information: NCT03276013.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Vall d’Hebron Institute of Oncology (VHIO).
Funding
MSD.
Disclosure
A. Oaknin: Full / Part-time employment: Vall d’Hebron Univeristy Hospital; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Immunogen; Advisory / Consultancy: Genmab. L. Fariñas Madrid: Advisory / Consultancy: Tesaro; Speaker Bureau / Expert testimony: Roche. A. Redondo: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: PharmaMar; Research grant / Funding (institution): Eisai. A. González Martín: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy, Speaker Bureau / Expert testimony: PharmaMar; Advisory / Consultancy: GenMab. I. Romero: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Tesaro; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: PharmaMar. J. Garcia-Donas: Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: GammaMabs; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol Meiers; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Squibb; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Honoraria (institution), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: BioClin. A. Gallego Martínez: Advisory / Consultancy: PharmaMar; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Tesaro. M.D. Fenor de la Maza Lopez Olmedo: Honoraria (institution), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (institution): Pierre Fabre; Travel / Accommodation / Expenses: BMS; Travel / Accommodation / Expenses: Pfizer; Travel / Accommodation / Expenses: Janssen. V. Rodriguez Freixinos: Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: PharmaMar. J.M. Piulats Rodriguez: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck Serono; Advisory / Consultancy: Novartis; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Clovis; Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy: Roche; Advisory / Consultancy: BeiGene; Advisory / Consultancy: VCN Biosciences; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Pfizer; Travel / Accommodation / Expenses: Ipsen. All other authors have declared no conflicts of interest.
Resources from the same session
5063 - Does Nutritional Status Affect Treatment Tolarability, Response and Survival in Metastatic Gastric Cancer Patients? Results of Prospective Multicenter Study
Presenter: Senem Karabulut
Session: Poster Display session 2
Resources:
Abstract
2717 - Ramucirumab use in patients with Advanced Gastric Cancer (AGC) or gastro-oesophageal junction (GEJ) adenocarcinoma in Spain: RAMIS observational study
Presenter: Federico Longo Munoz
Session: Poster Display session 2
Resources:
Abstract
3187 - Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor: Exploratory analysis in the patients who were enrolled in JCOG0705/KGCA01 phase III trial (REGATTA) and could continue chemotherapy
Presenter: Takaki Yoshikawa
Session: Poster Display session 2
Resources:
Abstract
4765 - A prospective observational study on the optimal maintenance strategy in HER2-positive advanced gastric cancer treated with trastuzumab based therapy
Presenter: Qian Li
Session: Poster Display session 2
Resources:
Abstract
3500 - Randomised phase 2 trial of first-line docetaxel, carboplatin, capecitabine (CTX) and epirubicin, oxaliplatin, capecitabine (EOX) in advanced esophagogastric adenocarcinoma (SEED)
Presenter: Peter Petersen
Session: Poster Display session 2
Resources:
Abstract
5197 - Ramucirumab in the treatment of refractory metastatic gastric cancer: results from the RamSelGa trial.
Presenter: Alexey Tryakin
Session: Poster Display session 2
Resources:
Abstract
2011 - Regorafenib in combination with Paclitaxel for beyond first-line treatment of advanced esophagogastric cancer (REPEAT): a phase Ib trial with expansion cohort
Presenter: Mohammed Khurshed
Session: Poster Display session 2
Resources:
Abstract
2117 - The relationship between the survival and fixed dosing of S-1 in advanced gastric cancer patients by pooled analysis using individual data from four Japanese randomized phase III trials
Presenter: Wataru Ichikawa
Session: Poster Display session 2
Resources:
Abstract
2669 - A Phase 1b Study of Oraxol in Combination with Ramucirumab in Patients with Gastric or Esophageal Cancers who failed previous chemotherapy
Presenter: Ming Huang Chen
Session: Poster Display session 2
Resources:
Abstract
3240 - Efficacy and safety of trifluridine/tipiracil (FTD/TPI) in European patients with heavily pretreated metastatic gastric cancer (mGC): an analysis of the TAGS study
Presenter: Maria Alsina
Session: Poster Display session 2
Resources:
Abstract