1785TiP - PERELI, a phase II, open label, multicenter study of pemigatinib and retifanlimab in advanced dedifferentiated liposarcoma

Background

Dedifferentiated liposarcomas (DDLPS) are highly malignant soft tissue sarcomas lacking efficient oncological treatment. Immunotherapy with PD-1 inhibitors has demonstrated limited activity in DDLPS as monotherapy. One strategy to improve the effectiveness of immunotherapy is to combine treatment with other anti-neoplastic agents, such as tyrosine kinase inhibitors. Alterations in the fibroblast growth factor receptor (FGFR) pathway are frequent in DDLPS. Preclinical data show that FGFR inhibitors can have an antitumor effect both in vitro and in vivo in tumors harboring changes in the FGFR pathway. FGFR inhibitors can also induce pro-immunogenic changes in the tumor microenvironment, further supporting the rationale for combination treatment. The PERELI trial is the first to explore the combination of FGFR inhibition with PD-1 inhibition in DDLPS.

Trial design

The PERELI study is a multicenter, open label phase II study assessing the efficacy and safety of the PD-1 inhibitor retifanlimab in combination with the FGFR inhibitor pemigatinib in adult patients with locally advanced (inoperable) or metastatic DDLPS. The primary endpoint is the progression free survival rate (PFSR) at 24 weeks. Eligible patients will have histologically confirmed MDM2-amplified DDLPS, ECOG performance status 0-2, measurable disease per RECIST v1.1 and received at least one line of prior systemic treatment. Thirty-three patients will be enrolled. After an induction phase with two cycles pemigatinib 13.5 mg once daily two weeks on, one week off, for six weeks, patients will receive the combination treatment with pemigatinib 13.5mg once daily two weeks on, one week off, and retifanlimab 375 mg on day 1 every 21 days. Treatment will continue until progression or intolerable toxicity. Secondary endpoints include overall response rate at 24 weeks, overall survival, safety and tolerability of the combination treatment. Exploratory objectives include analysis of pre-treatment and on-treatment tumor tissue for treatment-induced changes in tumor microenvironment as well as tissue biomarkers and analysis of circulating tumor DNA. Enrollment is ongoing.

Clinical trial identification

EU trial 2022-501993-21-00.

Editorial acknowledgement

Legal entity responsible for the study

Region Skåne.

Funding

Incyte, Svenska Sarkomföreningen, Berta Kamprad Stiftelse.

Disclosure

A. Carneiro: Financial Interests, Personal, Other, IO panel - open online: BMS; Financial Interests, Personal, Invited Speaker, Brain metastases lecture - open online: Pierre Fabre; Financial Interests, Personal, Advisory Board, Advisory Board, agenda on demand: Novartis; Financial Interests, Personal, Advisory Board, Advisory board, agenda on demand: MSD; Financial Interests, Institutional, Advisory Board, Project consultancy: Baxter; Financial Interests, Institutional, Other, Data Review Committee: Transgene; Non-Financial Interests, Principal Investigator, Principal investigator in several Phase I, 2 and 3 trials. Institutional agreement. No compensation for PI role. Specific information on demand.: Several. K. Boye: Financial Interests, Institutional, Advisory Board, Expert testimony on national applications to regulatory authorities: Bayer; Financial Interests, Institutional, Invited Speaker: Eli Lilly; Financial Interests, Personal, Advisory Board: Bayer, GSK, Incyte, NEC Oncoimmunity, Deciphera; Financial Interests, Personal, Invited Speaker: Deciphera; Financial Interests, Institutional, Research Grant: Eli Lilly; Non-Financial Interests, Principal Investigator: Deciphera, Novartis, Boehringer Ingelheim; Non-Financial Interests, Institutional, Product Samples: Merck. All other authors have declared no conflicts of interest.