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

J 2021

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

FALCHOOK, Gerald S., Marc PEETERS, Sylvie ROTTEY, Luc Y. DIRIX, Radka OBERMANNOVÁ et. al.

Basic information

Original name

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

Authors

FALCHOOK, Gerald S. (guarantor), Marc PEETERS, Sylvie ROTTEY, Luc Y. DIRIX, Radka OBERMANNOVÁ (203 Czech Republic, belonging to the institution), Jonathan E. COHEN, Ruth PERETS, Ronnie Shapir FROMMER, Todd M. BAUER, Judy S. WANG, Richard D. CARVAJAL, Joshua SABARI, Sonya CHAPMAN, Wei ZHANG, Boris CALDERON and Daniel A. PETERSON

Edition

Investigational New Drugs, DORDRECHT, SPRINGER, 2021, 0167-6997

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.651

RIV identification code

RIV/00216224:14110/21:00124645

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1007/s10637-021-01088-4

UT WoS

000640164300001

Keywords in English

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

Abstract

V originále

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): PartA = 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.

Citovat

FALCHOOK, Gerald S., Marc PEETERS, Sylvie ROTTEY, Luc Y. DIRIX, Radka OBERMANNOVÁ, Jonathan E. COHEN, Ruth PERETS, Ronnie Shapir FROMMER, Todd M. BAUER, Judy S. WANG, Richard D. CARVAJAL, Joshua SABARI, Sonya CHAPMAN, Wei ZHANG, Boris CALDERON and Daniel A. PETERSON. A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. Investigational New Drugs. DORDRECHT: SPRINGER, 2021, vol. 39, No 5, p. 1284-1297. ISSN 0167-6997. Available from: https://dx.doi.org/10.1007/s10637-021-01088-4.

@article{1854526,
   author = {Falchook, Gerald S. and Peeters, Marc and Rottey, Sylvie and Dirix, Luc Y. and Obermannová, Radka and Cohen, Jonathan E. and Perets, Ruth and Frommer, Ronnie Shapir and Bauer, Todd M. and Wang, Judy S. and Carvajal, Richard D. and Sabari, Joshua and Chapman, Sonya and Zhang, Wei and Calderon, Boris and Peterson, Daniel A.},
   article_location = {DORDRECHT},
   article_number = {5},
   doi = {http://dx.doi.org/10.1007/s10637-021-01088-4},
   keywords = {Advanced solid cancer; CSF-1; CSF-1R inhibitor; LY3022855; NSCLC; Ovarian cancer},
   language = {eng},
   issn = {0167-6997},
   journal = {Investigational New Drugs},
   title = {A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors},
   url = {https://link.springer.com/article/10.1007/s10637-021-01088-4},
   volume = {39},
   year = {2021}
}

TY  - JOUR
ID  - 1854526
AU  - Falchook, Gerald S. - Peeters, Marc - Rottey, Sylvie - Dirix, Luc Y. - Obermannová, Radka - Cohen, Jonathan E. - Perets, Ruth - Frommer, Ronnie Shapir - Bauer, Todd M. - Wang, Judy S. - Carvajal, Richard D. - Sabari, Joshua - Chapman, Sonya - Zhang, Wei - Calderon, Boris - Peterson, Daniel A.
PY  - 2021
TI  - A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors
JF  - Investigational New Drugs
VL  - 39
IS  - 5
SP  - 1284-1297
EP  - 1284-1297
PB  - SPRINGER
SN  - 01676997
KW  - Advanced solid cancer
KW  - CSF-1
KW  - CSF-1R inhibitor
KW  - LY3022855
KW  - NSCLC
KW  - Ovarian cancer
UR  - https://link.springer.com/article/10.1007/s10637-021-01088-4
N2  - 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): PartA = 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.
ER  -

FALCHOOK, Gerald S., Marc PEETERS, Sylvie ROTTEY, Luc Y. DIRIX, Radka OBERMANNOVÁ, Jonathan E. COHEN, Ruth PERETS, Ronnie Shapir FROMMER, Todd M. BAUER, Judy S. WANG, Richard D. CARVAJAL, Joshua SABARI, Sonya CHAPMAN, Wei ZHANG, Boris CALDERON and Daniel A. PETERSON. A phase 1a/1b trial of CSF-1R inhibitor LY3022855 in combination with durvalumab or tremelimumab in patients with advanced solid tumors. \textit{Investigational New Drugs}. DORDRECHT: SPRINGER, 2021, vol.~39, No~5, p.~1284-1297. ISSN~0167-6997. Available from: https://dx.doi.org/10.1007/s10637-021-01088-4.

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