Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Oct;39(5):1284-1297.
doi: 10.1007/s10637-021-01088-4. Epub 2021 Apr 14.

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Gerald S Falchook  1 , Marc Peeters  2 , Sylvie Rottey  3 , Luc Y Dirix  4 , Radka Obermannova  5 , Jonathan E Cohen  6   7 , Ruth Perets  8   9 , Ronnie Shapira Frommer  10 , Todd M Bauer  11 , Judy S Wang  12 , Richard D Carvajal  13 , Joshua Sabari  14 , Sonya Chapman  15 , Wei Zhang  16 , Boris Calderon  16 , Daniel A Peterson  16
Affiliations
Clinical Trial

A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors

Gerald S Falchook et al. Invest New Drugs. 2021 Oct.

Abstract

Background LY3022855 is a recombinant, immunoglobulin, human monoclonal antibody targeting the colony-stimulating factor-1 receptor. This phase 1 trial determined the safety, pharmacokinetics, and antitumor activity of LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid cancers who had received standard anti-cancer treatments. Methods In Part A (dose-escalation), patients received intravenous (IV) LY3022855 25/50/75/100 mg once weekly (QW) combined with durvalumab 750 mg once every two weeks (Q2W) IV or LY3022855 50 or 100 mg QW IV with tremelimumab 75/225/750 mg once every four weeks. In Part B (dose-expansion), patients with non-small cell lung cancer (NSCLC) or ovarian cancer (OC) received recommended phase 2 dose (RP2D) of LY3022855 from Part A and durvalumab 750 mg Q2W. Results Seventy-two patients were enrolled (median age 61 years): Part A = 33, Part B = 39. In Part A, maximum tolerated dose was not reached, and LY3022855 100 mg QW and durvalumab 750 mg Q2W was the RP2D. Four dose-limiting equivalent toxicities occurred in two patients from OC cohort. In Part A, maximum concentration, area under the concentration-time curve, and serum concentration showed dose-dependent increase over two cycles of therapy. Overall rates of complete response, partial response, and disease control were 1.4%, 2.8%, and 33.3%. Treatment-emergent anti-drug antibodies were observed in 21.2% of patients. Conclusions LY3022855 combined with durvalumab or tremelimumab in patients with advanced NSCLC or OC had limited clinical activity, was well tolerated. The RP2D was LY3022855 100 mg QW with durvalumab 750 mg Q2W. ClinicalTrials.gov ID: NCT02718911 (Registration Date: May 3, 2011).

Keywords: Advanced solid cancer; CSF-1; CSF-1R inhibitor; LY3022855; NSCLC; Ovarian cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yin Z, Bai L, Li W, Zeng T, Tian H, Cui J (2019) Targeting T cell metabolism in the tumor microenvironment: an anti-cancer therapeutic strategy. J Exp Clin Cancer Res 38(1):403. https://doi.org/10.1186/s13046-019-1409-3 - DOI - PubMed - PMC
    1. Thommen DS, Schumacher TN (2018) T cell dysfunction in Cancer. Cancer Cell 33(4):547–562. https://doi.org/10.1016/j.ccell.2018.03.012 - DOI - PubMed - PMC
    1. Buchbinder EI, Desai A (2016) CTLA-4 and PD-1 pathways: similarities, differences, and implications of their inhibition. Am J Clin Oncol 39(1):98–106. https://doi.org/10.1097/COC.0000000000000239 - DOI - PubMed - PMC
    1. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Rutkowski P, Lao CD, Cowey CL, Schadendorf D, Wagstaff J, Dummer R, Ferrucci PF, Smylie M, Hogg D, Hill A, Marquez-Rodas I, Haanen J, Guidoboni M, Maio M, Schoffski P, Carlino MS, Lebbe C, McArthur G, Ascierto PA, Daniels GA, Long GV, Bastholt L, Rizzo JI, Balogh A, Moshyk A, Hodi FS, Wolchok JD (2019) Five-year survival with combined Nivolumab and Ipilimumab in advanced melanoma. N Engl J Med 381(16):1535–1546. https://doi.org/10.1056/NEJMoa1910836 - DOI
    1. Gonzalez-Martin A, Sanchez-Lorenzo L (2019) Immunotherapy with checkpoint inhibitors in patients with ovarian cancer: still promising? Cancer 125(Suppl 24):4616–4622. https://doi.org/10.1002/cncr.32520 - DOI - PubMed

Publication types

MeSH terms

Associated data

LinkOut - more resources