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
1049 - The Effect Of Multiple Interventions For Women At Risk For Cervical Cancer On Their Health Responsibility, Beliefs Regarding Cervical Cancer, And Having Screening: A Randomized Controlled Experiment
Presenter: Busra Altinel
Session: Poster Display session 2
Resources:
Abstract
1309 - Quantifying the Effects of the Korean National Cancer Screening Program on Cervical Cancer Mortality
Presenter: Nhung Bui
Session: Poster Display session 2
Resources:
Abstract
1346 - Spread of tumor and adverse events after modified radical hysterectomy for FIGO Stage IB1 cervical cancer patients with tumor diameter preoperatively estimated 2 cm or less: Japan Clinical Oncology Group trial (JCOG1101); exploratory analysis before primary analysis.
Presenter: Takahide Arimoto
Session: Poster Display session 2
Resources:
Abstract
5352 - Impact of Combined Interstitial and Intracavitary Brachytherapy in locally advanced Cervical cancer: A Survival and toxicity profile assessment
Presenter: Vibhay Pareek
Session: Poster Display session 2
Resources:
Abstract
2049 - Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer
Presenter: Chel Hun Choi
Session: Poster Display session 2
Resources:
Abstract
1923 - Disparities starting adjuvant chemotherapy for locally advanced cervix cancer in the international, academic, randomised, phase 3 OUTBACK trial (ANZGOG 0902, RTOG 1174, NRG 0274)
Presenter: Linda Mileshkin
Session: Poster Display session 2
Resources:
Abstract
3284 - Primary results from CECILIA, a global single-arm phase 2 study evaluating bevacizumab (BEV), carboplatin (C) and paclitaxel (P) for advanced cervical cancer (aCC)
Presenter: Andres Redondo
Session: Poster Display session 2
Resources:
Abstract
843 - Prognostic and clinicopathological significance of PD-L1 in patients with cervical cancer: a meta-analysis
Presenter: Xiaobin Gu
Session: Poster Display session 2
Resources:
Abstract
1020 - Clinical impact of molecular profiling of cervical cancer (CC) patients (pts) in a dedicated Phase I (P1) unit
Presenter: Mariana Scaranti
Session: Poster Display session 2
Resources:
Abstract
872 - Comparative proteomic profiles of cervical cancer and paried paracancerous tissue and the potential effects of DUSP7 over-expression through inhibiting RAS pathway on the biological characteristics of human cervical cancer cell line SIHA
Presenter: Xuan Jiang
Session: Poster Display session 2
Resources:
Abstract