3567 - High clinical benefit rates of pembrolizumab in very rare sarcoma histotypes: first results of the AcSé Pembrolizumab study

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.