Abstract 3567
Background
AcSé Pembrolizumab is a Phase II, non-randomized parallel arm, open-label, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with rare cancers (NCT03012620). Here we report the first results of pembrolizumab in the sarcoma arm including chordomas, alveolar soft part sarcoma (ASPS), rhabdoid tumors, SMARCA4 deficient sarcomas and desmoplastic small round cell tumors (DSRCT).
Methods
Selected histotypes were all rare sarcomas (incidence <0.2/100000/year). Main inclusion criteria were age>18, PS ≤ 1, and advanced disease resistant to standard treatment. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycle for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to RECIST v1.1. Secondary endpoints included clinical benefit rate, duration of response, progression-free survival (PFS), overall survival (OS), and safety.
Results
21 patients with a primary diagnosis of chordoma (n = 12, 57%), ASPS (n = 6, 28%), or DSRCT, rhabdoid tumor and SMARCA4-deficient sarcoma (n = 3, 15%) were included from October 2017 to October 2018. The median number of cycle was 11 (range 1-23) with 9 (42.9%) patients who discontinued the trial after a median of 5 cycles. Three patients died after a median of 2 cycles due to progression (n = 2) or an unrelated cause (n = 1, trauma). For the population, the complete response/partial response (PR)/stable disease (SD) rates was 85% with 3 (15%) patients who achieved PR (DSRCT, rhabdoid, chordoma) and 16 (80%) with SD, after a median follow-up of 7.7 months (range 0-15.2). The median PFS was 11.5 months, the 6-month PFS was 61.5% and the 6-month OS was 85.2%. In subgroup analyses, the median PFS was 5.7 months for patients with chordoma and not reached for patients with ASPS. The 6-month OS rate was 75% in chordomas and 100% in the ASPS cohort. The basal clinical (histology) or biological (potassium, C-reactive protein, and lymphocyte levels) parameters tested were not predictive factors of PFS. The toxicity profile was similar to that observed in other cancers.
Conclusions
Pembrolizumab shows high levels of prolonged activity in selected subtypes of rare sarcomas.
Clinical trial identification
NCT03012620 EudraCT 2016-002260-14.
Editorial acknowledgement
Legal entity responsible for the study
R&D UNICANCER.
Funding
La Ligue Nationale contre le Cancer, Institut National du Cancer (INCa), MSD.
Disclosure
J. Blay: Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Honoraria (self), Honoraria (institution), Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Research grant / Funding (institution): Innate. C.M. Chevreau: Advisory / Consultancy: MSD. J. Soria: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: Gritstone; Advisory / Consultancy: Astex; Advisory / Consultancy: Clovis; Advisory / Consultancy: GSK; Advisory / Consultancy: GammaMabs; Advisory / Consultancy: Lilly; Advisory / Consultancy: MSD; Advisory / Consultancy: Mission Therapeutics; Advisory / Consultancy: Merus; Advisory / Consultancy: Pfizer; Advisory / Consultancy: PharmaMar; Advisory / Consultancy: Pierre Fabre; Advisory / Consultancy: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: Servier; Advisory / Consultancy: Symphogen; Advisory / Consultancy: Takeda. C. Massard: Advisory / Consultancy: Amgen; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: CelGene; Advisory / Consultancy: Debiopharm; Advisory / Consultancy: Genentech; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: MedImmune; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy: Orion; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Advisory / Consultancy: Astellas; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy: BeiGene; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: CelGene; Advisory / Consultancy: Debiopharm. All other authors have declared no conflicts of interest.
Resources from the same session
5678 - Nanomaterials Augmented LDI-TOF-MS for Hepatocellular Carcinoma Diagnosis and Classification
Presenter: Jian Zhou
Session: Poster Display session 3
Resources:
Abstract
2436 - Development and Validation of an RNA-Seq Assay for Gene Fusions Detection in Formalin-Fixed Paraffin-Embedded Samples
Presenter: Hua Dong
Session: Poster Display session 3
Resources:
Abstract
5271 - A Pilot Study to Implement an Artificial Intelligence (AI) System for Gastrointestinal Cancer Clinical Trial Matching
Presenter: Zhaohui Jin
Session: Poster Display session 3
Resources:
Abstract
4787 - A Blinded Comparison of Patient Treatments to Therapeutic Options Presented by an Artificial Intelligence-based Clinical Decision-support system
Presenter: Suthida Suwanvecho
Session: Poster Display session 3
Resources:
Abstract
5744 - OncOS: scalable and accurate next-generation sequencing analytics for precision oncology and personalized patient care
Presenter: Joe Thompson
Session: Poster Display session 3
Resources:
Abstract
3752 - The association between wearable device physical activity metrics and performance status in oncology: a systematic review
Presenter: Milan Kos
Session: Poster Display session 3
Resources:
Abstract
5820 - SomaticNET: neural network evaluation of somatic mutations in cancer
Presenter: Geoffroy Dubourg-Felonneau
Session: Poster Display session 3
Resources:
Abstract
4771 - Is there a role for Next-generation sequencing (NGS) profiling on metastatic non-colorectal gastrointestinal carcinomas (MNCGIC) in developing countries? A single center experience.
Presenter: Mauricio Ribeiro
Session: Poster Display session 3
Resources:
Abstract
1209 - Metastatic Cancer Whole-Exome Sequencing in daily practice
Presenter: Manon Réda
Session: Poster Display session 3
Resources:
Abstract
5702 - Genomic-Guided Individualized Precision Therapy in Refractory Metastatic Solid Tumor Patients with Extensively Poor Performance Status: A Chinese single institutional prospective observational real-world study
Presenter: Haitao Wang
Session: Poster Display session 3
Resources:
Abstract