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
4900 - Molecular profiling and prognostic significance of TP53 mutations in Diffuse Large B Cell Lymphoma: identifying a high-risk subgroup
Presenter: Yuan-Kai Shi
Session: Poster Display session 3
Resources:
Abstract
3809 - Differential expression of various miRNAs in Pediatric Cytogenetically Normal Acute Myeloid Leukemia (CN-AML)
Presenter: Vikas Gaur
Session: Poster Display session 3
Resources:
Abstract
4750 - Circulating tumour cells in head and neck and non-small cell lung cancer
Presenter: Kenneth O'Byrne
Session: Poster Display session 3
Resources:
Abstract
3704 - OX40/OX40L protein expression in Non-small cell lung cancer and its role in clinical outcome and relationships with other immune biomarkers
Presenter: Xiaoshen Zhang
Session: Poster Display session 3
Resources:
Abstract
2235 - Effect of Serum Survivin on Survival among Non-Small Cell Lung Cancer Patients; NCI Experience
Presenter: Reham Rashed
Session: Poster Display session 3
Resources:
Abstract
2788 - Enhanced performance of prognostic estimation from TCGA RNAseq data using transfer learning.
Presenter: Helene Vanacker
Session: Poster Display session 3
Resources:
Abstract
4689 - Analysis of Circulating Tumor DNA for Early Relapse Detection in Stage III Colorectal Cancer After Adjuvant Chemotherapy
Presenter: Samuel Jacobs
Session: Poster Display session 3
Resources:
Abstract
1454 - Ascites-derived circulating microRNAs as potential diagnostic biomarkers of gastric cancer-associated malignant ascites
Presenter: Hye Sook Han
Session: Poster Display session 3
Resources:
Abstract
5574 - Results from TRIO030, a Pre-Surgical Tissue-Acquisition Study to Evaluate Molecular Alterations in Human Breast Cancer Tissue Following Short-Term Exposure to the Androgen Receptor Antagonist Darolutamide
Presenter: Hsiao-Wang Chen
Session: Poster Display session 3
Resources:
Abstract
1787 - JMJD2A is a novel epigenetic factor of chemotherapeutic susceptibility in gastric cancer
Presenter: Yasushi Sato
Session: Poster Display session 3
Resources:
Abstract