PMID- 38349570
OWN - NLM
STAT- MEDLINE
DCOM- 20240214
LR  - 20240309
IS  - 1432-0851 (Electronic)
IS  - 0340-7004 (Print)
IS  - 0340-7004 (Linking)
VI  - 73
IP  - 3
DP  - 2024 Feb 13
TI  - INDUCE-2: A Phase I/II, open-label, two-part study of feladilimab in combination 
      with tremelimumab in patients with advanced solid tumors.
PG  - 44
LID - 10.1007/s00262-023-03623-z [doi]
LID - 44
AB  - Combining immunotherapies with distinct mechanisms of action has the potential to 
      overcome treatment resistance and improve outcomes. The inducible T-cell 
      co-stimulator (ICOS) agonist feladilimab is directed at enhancing T-cell 
      activation and function, thereby promoting an antitumor response. INDUCE-2 
      (NCT03693612) was a Phase I/II, open-label, two-part study evaluating the 
      anti-ICOS agonist feladilimab in combination with the anti-CTLA-4 antibody 
      tremelimumab in patients with select advanced solid tumors. Objectives of Part 1 
      were to determine the safety, tolerability, and recommended phase 2 dose (RP2D) 
      of feladilimab in combination with tremelimumab. In Part 2, the antitumor 
      activity of the combination (administered at the RP2D determined in Part 1) was 
      to be assessed in patients with relapsed/refractory head and neck squamous cell 
      carcinoma. Primary endpoints included the rates of dose-limiting toxicities 
      (DLTs), adverse events (AEs), AEs of special interest, and serious AEs. Secondary 
      endpoints included overall response rate, while biomarker assessment was 
      exploratory. A total of 26 patients were enrolled, 18 (69%) of whom had completed 
      the study at end date. One patient, in the highest dose group (24/225 mg 
      feladilimab/tremelimumab), experienced a DLT 18 days after the first dose of 
      study treatment. All patients experienced at least one AE; AEs led to treatment 
      discontinuation in four (15%) patients. Partial response was observed in one 
      patient. Feladilimab in combination with tremelimumab was well-tolerated but 
      showed limited efficacy. Based on the totality of data from Part 1, it was 
      decided not to continue with Part 2.
CI  - (c) 2024. The Author(s).
FAU - Hilton, John F
AU  - Hilton JF
AD  - The Ottawa Hospital Cancer Centre, Ottawa, ON, Canada.
FAU - Ott, Patrick A
AU  - Ott PA
AD  - Dana Farber Cancer Institute, Boston, MA, USA.
FAU - Hansen, Aaron R
AU  - Hansen AR
AD  - Princess Margaret Cancer Centre, Toronto, ON, Canada.
FAU - Li, Zujun
AU  - Li Z
AD  - New York University, New York, NY, USA.
FAU - Mathew, Matthen
AU  - Mathew M
AUID- ORCID: 0000-0003-3254-0039
AD  - Columbia University Irving Medical Center, New York, NY, USA.
FAU - Messina, Cristina H
AU  - Messina CH
AD  - GSK, Collegeville, PA, USA.
FAU - Dave, Vimal
AU  - Dave V
AD  - GSK, Bengaluru, Karnataka, India.
FAU - Ji, Xiao
AU  - Ji X
AD  - GSK, Collegeville, PA, USA.
FAU - Karpinich, Natalie O
AU  - Karpinich NO
AD  - GSK, Collegeville, PA, USA.
FAU - Hirschfeld, Steven
AU  - Hirschfeld S
AD  - GSK, Collegeville, PA, USA.
FAU - Ballas, Marc
AU  - Ballas M
AD  - GSK, Collegeville, PA, USA.
FAU - Zandberg, Dan P
AU  - Zandberg DP
AUID- ORCID: 0000-0002-1002-8301
AD  - UPMC Hillman Cancer Center, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA. 
      zandbergdp@upmc.edu.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20240213
PL  - Germany
TA  - Cancer Immunol Immunother
JT  - Cancer immunology, immunotherapy : CII
JID - 8605732
RN  - QEN1X95CIX (tremelimumab)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Monoclonal)
SB  - IM
MH  - Humans
MH  - *Antibodies, Monoclonal, Humanized/therapeutic use
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Immunotherapy
MH  - *Head and Neck Neoplasms
PMC - PMC10864474
OTO - NOTNLM
OT  - Biomarkers
OT  - Clinical-trial results
OT  - Immunology
OT  - Immunotherapy
OT  - Tumor microenvironment
COIS- JFH: advisory/consulting for Bristol Myers Squibb, AstraZeneca, Pfizer, Novartis, 
      Eli-Lilly, and Merck; member of a DMC Committee for Bristol Myers Squibb. PAO: 
      grants/research support recipient from Neon Therapeutics, Bristol Myers Squibb, 
      Merck, AstraZeneca /MedImmune, ArmoBiosciences, Pfizer, Novartis, CytomX, 
      Genentech, Celldex; ad hoc consulting for Neon Therapeutics, Bristol Myers 
      Squibb, Merck, ArmoBiosciences, Pfizer, Novartis, CytomX, Genentech, Celldex, 
      Array; scientific advisory board for Evaxion, Phio, and Immunetune. ARH: 
      advisory/consulting and research support from Genentech/Roche, Merck, GSK, 
      Bristol Myers Squibb, Novartis, Boston Biomedical, Boehringer Ingelheim. ZL: 
      advisory/board member and honorarium recipient for Boehringer Ingelheim. MM: 
      equity in Navinta. CHM, VD, and MB: former employees of and hold stocks/shares in 
      GSK. XJ, NOK, SH: employees of and hold stocks/shares in GSK. DPZ: advisory for 
      Blueprint Medicines and Prelude Therapeutics; consulting for Macrogenics; 
      research support for role as principal investigator from Merck, Bristol Myers 
      Squibb, AstraZeneca, GSK, Aduro, Astellas, Macrogenics, Lilly, Bicara, Checkmate 
      Pharma, Novasenta.
EDAT- 2024/02/13 12:47
MHDA- 2024/02/14 12:47
PMCR- 2024/02/13
CRDT- 2024/02/13 11:20
PHST- 2023/08/31 00:00 [received]
PHST- 2023/12/25 00:00 [accepted]
PHST- 2024/02/14 12:47 [medline]
PHST- 2024/02/13 12:47 [pubmed]
PHST- 2024/02/13 11:20 [entrez]
PHST- 2024/02/13 00:00 [pmc-release]
AID - 10.1007/s00262-023-03623-z [pii]
AID - 3623 [pii]
AID - 10.1007/s00262-023-03623-z [doi]
PST - epublish
SO  - Cancer Immunol Immunother. 2024 Feb 13;73(3):44. doi: 10.1007/s00262-023-03623-z.