1720MO - A phase II study of palbociclib combined with the PD-1 inhibitor retifanlimab in patients with advanced dedifferentiated liposarcoma

Background

The CDK4/6 inhibitor palbociclib (P) has demonstrated promising clinical activity in DDLPS patients (pts). In pre-clinical models, CDK4/6 inhibitors synergize with anti-PD-1 therapy by upregulating antigen processing and presentation, increasing tumor-infiltrating lymphocytes, and decreasing regulatory T cells.

Methods

NCT04438824 is an investigator-initiated phase II study of P plus retifanlimab (R) in patients with recurrent, unresectable, or metastatic DDLPS. Up to 30 pts will receive concurrent P (125 mg once daily orally for 21 days followed by 7 days off) plus R (500 mg IV flat dose every 4 weeks) in 28-day cycles. The primary endpoint is to estimate the best objective response rate (ORR) by RECIST 1.1. An ORR of 5% was considered not promising and 25% considered promising. Four or more pts with a confirmed objective response are needed to reject the null hypothesis. This single-stage design has a type I error rate of 0.06 and a type II error rate of 0.04. Secondary endpoints include describing the safety and estimating duration of response (DoR), disease control rate (DCR), progression-free (PFS), and overall survival (OS).

Results

Twenty-eight pts have been enrolled and treated at the time of data cutoff. Median pt age was 61 years (range, 36 – 81), most pts were male (64%) and had no prior systemic therapy (64%). Six pts (21.4%, 95% confidence interval [CI], 9 – 41.5%) had a best response of partial response (PR) by RECIST 1.1. Four PRs have been confirmed, yielding a confirmed ORR of 14.3% (95% CI 4.7 – 33.6%). The DCR was 50% (95% CI 32.6 - 67.4%). Median PFS and OS were 2.2 (1.8 – not reached [NR]) and 24.8 months (24.8 – NR), respectively. Median DoR has not yet been reached (9.4 – NR). Seventeen pts (61%) had 1 or more Grade ³ 3 treatment-related adverse event (TRAE). The most common, occurring in ³ 10% of pts, were neutropenia (39%), leukopenia (21%), increased ALT (14%), and increased AST (11%). One pt (4%) had a Grade 4 TRAE of neutropenia. There were no Grade 5 TRAEs.

Conclusions

This study of P plus R has met its primary endpoint. A subset of pts have deep and durable responses. Correlative work is ongoing to identify biomarkers of response and resistance to this treatment combination.

Clinical trial identification

NCT04438824.

Editorial acknowledgement

Legal entity responsible for the study

Memorial Sloan Kettering Cancer Center.

Funding

Incyte Corporation.

Disclosure

E. Rosenbaum: Financial Interests, Personal, Stocks/Shares: Iovance Biotherapeutics, PMV Pharmaceuticals; Financial Interests, Institutional, Local PI: Incyte Corporation, Arcus Biosciences, GSK. M. Dickson: Financial Interests, Institutional, Other: Sumitomo Dainippon Pharma Oncology, Aadi; Financial Interests, Institutional, Principal Investigator: Lilly. S. Movva: Financial Interests, Institutional, Coordinating PI: Tracon, Pfizer, Merck, BMS, Clovis, Ascentage; Financial Interests, Institutional, Local PI: PTC therapeutics, Hutchinson Medipharma. C.M. Kelly: Financial Interests, Personal, Invited Speaker, Educational presentations on GIST: Deciphera; Financial Interests, Personal, Advisory Board, Chondrosarcoma Adboard: Servier; Financial Interests, Personal, Advisory Board: Immunicum; Financial Interests, Personal, Invited Speaker, Panel discussant about GIST management: Deciphera; Financial Interests, Personal, Other, Clinical trial Safety review committee member: Kartos; Financial Interests, Personal, Other, Consultancy: Chemocentryx; Financial Interests, Personal, Writing Engagement, Educational article on sarcoma: PER; Financial Interests, Personal, Invited Speaker, Educational presentation on MCC management: More Health; Financial Interests, Personal, Full or part-time Employment, Spouse is employed by this company: Daiichi Sankyo; Financial Interests, Personal, Stocks/Shares, Spouse is employed by this company: Daiichi Sankyo; Financial Interests, Institutional, Coordinating PI: Servier, Amgen, Merck, Curadev; Financial Interests, Institutional, Local PI: Regeneron, IDRX, Inhibrx; Financial Interests, Personal, Steering Committee Member: Kartos. J. Chan: Financial Interests, Institutional, Other, Received antibodies in part of a collaboration for a grant.: Cytek; Financial Interests, Institutional, Other, My research work in lung cancer was funded as part of a sponsored research agreement between my PI and the company.: Ono Pharmaceutical. P. Chi: Financial Interests, Personal, Other, Advisor and Consultant: Ningbo NewBay Medical Technology; Financial Interests, Institutional, Funding, Clinical trial funding: Ningbo NewBay Medical Technology; Financial Interests, Personal and Institutional, Steering Committee Member, Clinical Trial: Ningbo NewBay Medical Technology, Deciphera; Financial Interests, Institutional, Funding, clinical trial: Deciphera; Financial Interests, Institutional, Funding, Trial: Pfizer. M. Gounder: Financial Interests, Personal, Other, Professional services and activities: Ayala Pharmaceuticals, Inc.; Financial Interests, Personal, Other, Professional services and activities: Bayer; Financial Interests, Personal, Other, Professional services and activities: Boehringer Ingelheim; Financial Interests, Personal, Other, Professional services and activities: Guidepoint Global Advisors; Financial Interests, Personal, Other, Professional services and activities: Karyopharm; Financial Interests, Personal, Other, Professional services and activities: Med Learning Group; Financial Interests, Personal, Other, Professional services and activities: Rain Therapeutics Inc.; Financial Interests, Personal, Other, Professional services and activities: Regeneron Pharmaceuticals Inc.; Financial Interests, Personal, Other, Professional services and activities: Springworks Therapeutics; Financial Interests, Personal, Other, Professional services and activities: Syneos Health; Financial Interests, Personal, Other, Professional services and activities: UptoDate. R.G. Maki: Financial Interests, Personal, Other, DSMB participation: Deciphera; Financial Interests, Personal, Other, Consultant to serve as Medical Monitor: Peel Therapeutics; Financial Interests, Personal, Invited Speaker, Sarcoma content for web site: Physician's Education Resource; Financial Interests, Personal, Writing Engagement, Sarcoma content editor: UptoDate; Financial Interests, Personal, Advisory Board, Advisory board: GSK; Financial Interests, Personal, Advisory Board: Medtronic; Financial Interests, Personal, Other, Associate Editor, JCO: American Society of Clinical Oncology; Financial Interests, Personal and Institutional, Coordinating PI, Clinical trial support and steering committee - brigimadlin studies: Boeringher Ingelheim; Financial Interests, Personal and Institutional, Coordinating PI, Investigator initiated trial with pembrolizumab: GSK. J.P. Erinjeri: Financial Interests, Personal, Other, Consultant: AstraZeneca. W.D. Tap: Financial Interests, Personal, Leadership Role: Certis Oncology Solutions, Atropos, Innova Therapeutics; Financial Interests, Personal, Advisory Role: EMD Serono, Lilly, Daiichi, Deciphera, C4, Mundipharma, Ascendo, Ayala Pharma, Kowa Pharma, Servier, Bayer, Epizyme, Cogent, Medpacto, Foghorn, Amgen; Financial Interests, Institutional, Research Funding: Novartis, Lilly, Plexxikon, Daiichi Sankyo, Tracon, Blueprint, Immune Design, Bioatla, Deciphera. S.P. D'Angelo: Financial Interests, Personal, Advisory Role: EMD Serono, Amgen, Nektar, Immune design, GSK, Incyte, Merck, Adaptimmiune, Immunocore; Financial Interests, Institutional, Research Funding: EMD Serono, Amgen, Merck, Incyte, Nektar, BMS, Deciphera; Financial Interests, Personal, Other, Travel: Adaptimmune, EMD Serono, Nektar. All other authors have declared no conflicts of interest.