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774 A phase 1 study exploring the safety and tolerability of the small molecule PD-L1 inhibitor, INCB086550, in patients with select advanced tumors
  1. Christophe Le Tourneau1,
  2. Sarina Piha-Paul2,
  3. Hans Prenen3,
  4. Brant Delafontaine4,
  5. David Pinato5,
  6. Armando Santoro6,
  7. Rebecca Kristeleit7,
  8. Kristen Spencer8,
  9. Tara Gangadhar9,
  10. Howard Burris10,
  11. Nuria Kotecki11,
  12. Bristi Basu12,
  13. Donna Graham13,
  14. Anna Maria Di Giacomo14,
  15. Solmaz Sahebjam15,
  16. Massimo Di Nicola16,
  17. Carlos Gomez-Roca17,
  18. Pascale Tomasini17,
  19. Paolo Ascierto18,
  20. Giuseppe Curigliano19,
  21. Thomas Karasic20,
  22. Ryan Geschwindt21,
  23. Jeannie Daniel21 and
  24. Eric Van Cutsem22
  1. 1Institut Curie, Paris, France
  2. 2University of Texas, Houston, TX, USA
  3. 3Universitair Ziekenhuis – Antwerpen, Antwerp, Belgium
  4. 4Drug Research Unit Ghent, Ghent, Belgium
  5. 5Imperial College London, London, UK
  6. 6Humanitas University, Rozzano-Milan, Italy
  7. 7Guy’s and St Thomas NHS Foundation Trust, London, UK
  8. 8Perlmutter Cancer Center of NYU, Langone health and NYU Grossman School of Medicine, New York, NY, USA
  9. 9Abramson Cancer Center, Philadelphia, PA, USA
  10. 10Tennessee Oncology, Nashville, TN, USA
  11. 11Institut Jules Bordet, Brussels, Belgium
  12. 12University of Cambridge, Cambridge, UK
  13. 13The Christie NHS Foundation Trust, Manchester, UK
  14. 14University of Siena, Siena, Italy
  15. 15Moffitt Cancer Center, Tampa, FL, USA
  16. 16Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy
  17. 17Assistance Publique Des Hôpitaux de Marseille, Marseille, France
  18. 18Istituto Nazionale Tumori, Milan, Italy
  19. 19European Institute of Oncology, Milan, Italy
  20. 20Perelman School of Medicine, Philadelphia, PA, USA
  21. 21Incyte Corporation, Wilmington, DE, USA
  22. 22University Hospitals Gasthuisberg, Leuven, Belgium


Background INCB086550 is an orally administered small-molecule inhibitor of programmed cell death ligand 1 (PD-L1). This is an ongoing phase 1, open-label, multicenter study.

Methods Eligible patients are aged ≥18 years with advanced solid tumors and Eastern Cooperative Oncology Group performance status of 0–1. Patients had disease progression after treatment with available therapies or were ineligible for or without access to standard treatment. Part 1 uses a modified 3+3 dose-escalation design to identify a maximum tolerated dose (MTD) of INCB086550. Multiple doses are expanded in additional cohorts: part 2 cohort A (tumors that progressed on previous PD-1 treatment), part 2 cohort B (immunotherapy-naive), part 3 (high microsatellite instability [MSI-H] or deficient mismatch repair), and part 4 (human papilloma virus–positive tumors). The primary endpoints were safety and tolerability measured by monitoring frequency and severity of adverse events (AEs) and to determine a pharmacologically active dose and/or MTD. Tumor response was evaluated per RECIST v1.1 or RANO.

Results As of April 1, 2022, 138 patients received INCB086550 treatment at doses ranging from 100 mg once daily to 800 mg twice daily (bid); median age was 65 years (range, 31–86), 60.9% were women, 80.4% were white. 78 patients (56.5%) had ≥2 lines of prior therapy. The most common tumor types were colorectal (13.8%), cervical (10.9%), and anal (10.9%). 121 patients (87.7%) discontinued treatment, 90 of whom discontinued for disease progression. Treatment-emergent AEs (TEAEs) occurring in >20% of patients were fatigue, nausea, decreased appetite, constipation, vomiting, and diarrhea. Serious TEAEs (SAEs) occurred in 50 patients (36.2%); SAEs occurring in >2 patients were small intestinal obstruction, abdominal pain, intestinal obstruction, and pneumonia. No dose-limiting toxicities (DLTs) occurred. Grade ≥3 treatment-related AEs occurred in 18 patients (13.0%), with aspartate aminotransferase increased, fatigue, immune-mediated neuropathy, and rash reported in >1 patient (n=2 each). Sponsor-defined immune-related TEAEs occurred in 41 patients (29.7%), 22 (15.9%) of which were peripheral neuropathies. Stepdown/intermittent dose regimens did not mitigate events of immune-mediated peripheral neuropathy. 16 patients (11.6%) had TEAEs that led to discontinuation of INCB086550. Two patients (1.4%) achieved a complete response (squamous cell anal cancer, 400 mg bid; MSI-H colorectal cancer, 400 mg bid); 10 patients overall (7.2%) achieved partial response.

Conclusions No DLTs occurred. Encouraging antitumor activity has been observed. INCB086550 has a safety profile consistent with monoclonal antibody immune checkpoint inhibitors, except for an observed increased rate of immune-mediated peripheral neuropathy.

Trial Registration NCT04629339

Ethics Approval This study was reviewed and approved by the institutional review boards of the participating institutions. Approval numbers are: EC/FAHMP (Belgium), P/2020-149; ARS/RHA (Regional Health Authority) (France), 2018-2610; AIFA (Italy), 133700; IRAS (UK), 282291; REC (UK), 20/LO/1001; (USA), RM 598, 1254008, 2018-0765, MOD00971017, 20182238, 1291221. All patients provided written informed consent.

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