A phase 2 study of pembrolizumab in combination with doxorubicin in advanced, recurrent or metastatic endometrial cancer

Date 29 September 2019
Event ESMO 2019 Congress
Session Poster Display session 2
Topics Endometrial Cancer
Presenter Ana Oaknin
Citation Annals of Oncology (2019) 30 (suppl_5): v403-v434. 10.1093/annonc/mdz250
Authors A. Oaknin1, M.J. RUBIO PEREZ2, L. FARIÑAS MADRID3, A. Redondo4, A. Yubero Esteban5, M. Gil Martín6, A. González Martín7, I. Romero8, J. Garcia-Donas9, R. Serrano10, A. Gallego Martínez11, M. Ocariz Diez12, M.L. Sanchez Lorenzo13, M.D. Fenor de la Maza Lopez Olmedo14, V. Rodriguez Freixinos15, J.M. Piulats Rodriguez16
  • 1Medical Oncology, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 2Medical Oncology Department, Reina Sofia University Hospital, 14004 - Cordoba/ES
  • 3Medical Oncology Dept., Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 4Oncología Médica, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 5Medical Oncology Dept., Hospital Clinico Universitario Lozano Blesa, 50009 - Zaragoza/ES
  • 6Medical Oncology Dept., ICO - Institut Catala d'Oncologia Hospital Duran i Reynals, 08907 - Hospitalet de Llobregat/ES
  • 7Medical Oncology Department, Clínica Universidad de Navarra, 28036 - Madrid/ES
  • 8Medical Oncology Department, IVO - Fundación Instituto Valenciano de Oncología, 46009 - Valencia/ES
  • 9Genitourinary, Ginecologycal, Skin And Rare Tumors Unit, Hospital Madrid Norte San Chinarro; Centro Integral Oncologico Clara Campal, 28050 - Madrid/ES
  • 10Medical Oncology Department, Hospital Universitario Reina Sofía, 14005 - Córdoba/ES
  • 11Medical Oncology, Hospital Universitario La Paz, 28046 - Madrid/ES
  • 12Dept. Medical Oncology, Hospital Clinico Universitario Lozano Blesa, 50009 - Zaragoza/ES
  • 13Medical Oncology, Clínica Universidad de Navarra, 28027 - Madrid/ES
  • 14Medical Oncology, Clara Campal Comprehensive Cancer Centre, 28050 - Madrid/ES
  • 15Medical Oncology Department, Vall d'Hebron University Hospital, 08035 - Barcelona/ES
  • 16Dept. Medical Oncology, ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), 08908 - Hospitalet de Llobregat/ES

Abstract

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.