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
3875 - Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract
5793 - Real world treatment sequencing patterns in secondary breast cancer (SBC): Pathway visualisation using national datasets.
Presenter: Ashley Horne
Session: Poster Display session 2
Resources:
Abstract
3185 - Utilization Pattern of Bone Targeting Agents in Patients with Solid Tumor in Taiwan, Hong Kong and Korea
Presenter: Shi Jie Lai
Session: Poster Display session 2
Resources:
Abstract
3705 - Clinico-pathological Features and Prognosis of Patients with Pregnancy Associated Breast Cancer – A Matched Case Control Study
Presenter: Ruyan Zhang
Session: Poster Display session 2
Resources:
Abstract
1421 - TRYbeCA-2: A Randomized Phase 2/3 Study of Eryaspase in Combination with Gemcitabine and Carboplatin Chemotherapy versus Chemotherapy Alone As First-Line Treatment in Patients with Metastatic or Locally Recurrent Triple-Negative Breast Cancer
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
4119 - CONTESSA TRIO: A Multinational, Multicenter, Phase 2 Study of Tesetaxel plus 3 Different PD-(L)1 Inhibitors in Patients with Metastatic Triple-Negative Breast Cancer (TNBC) and Tesetaxel Monotherapy in Elderly Patients with HER2- Metastatic Breast Cancer (MBC)
Presenter: Sara Tolaney
Session: Poster Display session 2
Resources:
Abstract
4545 - Bintrafusp alfa (M7824) and Eribulin Mesylate in Treating Patients With Metastatic Triple Negative Breast Cancer (TNBC)(NCT03579472)
Presenter: Jennifer Litton
Session: Poster Display session 2
Resources:
Abstract
3340 - Effectiveness of Olaparib Plus Trastuzumab in HER2[+], BRCA–mutated (BRCAm) or Homologous Recombination Deficient (HRD) Advanced Breast Cancer (ABC) patients (pts). The OPHELIA Study
Presenter: José Enrique Alés-Martínez
Session: Poster Display session 2
Resources:
Abstract
1113 - RIBOB : A Study on the efficacy and safety of Ribociclib in combination with letrozole in Older women (≥70 years) with hormone receptor-positive (HR+) HER2-negative (HER2-) advanced Breast cancer (aBC) with no prior systemic therapy for advanced disease
Presenter: Cindy Kenis
Session: Poster Display session 2
Resources:
Abstract
4025 - RIbociclib plus Goserelin with Hormonal Therapy versus physician Choice chemotherapy in premenopausal or perimenopausal patients with HR+, HER2– inoperable locally advanced or metastatic breast cancer – RIGHT Choice study
Presenter: Nagi El Saghir
Session: Poster Display session 2
Resources:
Abstract