Abstract 1669TiP
Background
Treatment of soft tiusse sarcoma (STS) with the combination of trabectedin and the anti-PD1 antibody nivolumab suggests to be a promising treatment approach as the combination produces a synergistic antitumor effect in a murine model of ovarian cancer. Moreover, the antitumor activity of trabectedin is partially mediated by macrophage depletion and different immunologic effects. Thus, it seems reasonable to evaluate the efficacy and safety of trabectedin plus nivolumab as a second-line option in anthracycline-pretreated sarcomas.
Trial design
This is a prospective phase II NiTraSarc trial consisting of two parallel groups: Group A includes patients with liposarcoma or leiomyosarcoma (abbreviated as L-sarcomas; n=55); whereas Group B comprise patients with non-L-sarcomas (n=37). Patients in both groups have unresectable or metastatic STS and have received a prior anthracycline-containing regimen. Initially, the enrolled patients are treated with three cycles of trabectedin monotherapy, given every three weeks (q3w), followed with the combination of trabectedin (1.5 mg/m2) plus nivolumab (240 mg) starting from cycle four (“late combination cohort”) for up to a total of 16 cycles q3w. A pre-planned interim safety evaluation was performed once nine patients had completed the third trabectedin plus nivolumab combination cycle. Due to absence of serious safety issues with this potentially more efficient therapy, the trial design was amended moving the start of combination therapy after only one cycle of trabectedin monotherapy (“early combination cohort”). All patients undergo tumor assessments after Cycle 3 and afterwards every 9 weeks ± 1 week until disease progression. Primary efficacy endpoint of the trial is progression-free survival (PFS) rate after 6 months (PFS-6) according to RECIST v.1.1. Secondary endpoints are overall response rate, overall survival, PFS and duration of disease stabilization. In May 2020, 82 of planned 92 patients have been enrolled. This trial is supported by PharmaMar and Bristol-Myers Squibb with drug and funding.
Clinical trial identification
NCT03590210; EudraCT: 2017-001083-38.
Editorial acknowledgement
Review by PharmaMar and Bristol-Myers Squibb.
Legal entity responsible for the study
Sponsor of the Study according to AMG is Universitätsmedizin Greifswald, Fleischmannstr. 8, 17475 Greifswald, Germany. Representative of the Sponsor: Dr. med. Daniel Pink Klinik für Hämatologie, Onkologie und Palliativmedizin, Sarkomzentrum Berlin-Brandenburg, HELIOS Klinikum Bad Saarow, Pieskower Str. 33, 15526 Bad Saarow, Email: daniel.pink@helios-kliniken.de.
Funding
PharmaMar & Bristol-Myers Squibb (drug and funding).
Disclosure
P. Reichardt: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Honoraria (self): PharmaMar; Honoraria (self): Lilly; Honoraria (self): Amgen; Advisory/Consultancy: Clinigen Group; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Deciphera; Advisory/Consultancy: MSD; Advisory/Consultancy: Bristol-Myers Squibb. V. Grünwald: Honoraria (self), Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: AstraZeneca; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options: Bristol-Myers Squibb; Shareholder/Stockholder/Stock options: MSD; Honoraria (self): Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Travel/Accommodation/Expenses: Bayer; Honoraria (self): Merck Serono; Honoraria (self): Asklepios Clinics ; Honoraria (self), Advisory/Consultancy: Janssen-Cilag; Honoraria (self): Diakonie Clinic; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self): PharmaMar; Honoraria (self): EUSAPharm; Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): Eisai; Honoraria (self): Dortmund Hospital; Honoraria (self): Clinic of Oldenburg; Advisory/Consultancy: Novartis; Advisory/Consultancy: Onkowissen. B. Kasper: Honoraria (self), Travel/Accommodation/Expenses, + scientific investigations: PharmaMar. E. Wardelmann: Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Nanobiotix; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer; Honoraria (self): Novartis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Advisory/Consultancy: New Oncology. S-E. Al-Batran: Advisory/Consultancy, Research grant/Funding (self): Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Celgene; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Lilly; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy, Research grant/Funding (self): Merck; Advisory/Consultancy, Speaker Bureau/Expert testimony: Nordic Bioscience; Advisory/Consultancy: Merck Sharp & Dohme; Speaker Bureau/Expert testimony: AIO gGmbH; Speaker Bureau/Expert testimony: Forum für Medizinische Fortbildung; Speaker Bureau/Expert testimony: MCI Group; Shareholder/Stockholder/Stock options, Since February 2020 \"Institut für Klinische Krebsforschung IKF GmbH\": IKF Klinische Krebsforschung ; Research grant/Funding (self): Medac; Research grant/Funding (self): Hospira; Research grant/Funding (self): Sanofi; Research grant/Funding (self): German Cancer Aid; Research grant/Funding (self): German Research Foundation; Research grant/Funding (self): General Ministryof Education and Research; Research grant/Funding (self): Vifor Pharma. D. Pink: Advisory/Consultancy, Research grant/Funding (institution): Lilly; Advisory/Consultancy, Research grant/Funding (institution): Clinigen; Advisory/Consultancy, Research grant/Funding (institution): Roche; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): PharmaMar. All other authors have declared no conflicts of interest.