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  • 1495 A phase 1 multicenter study of the safety and efficacy of the NKG2A targeting antibody S095029 as single agent and in combination with anti-PD1 in patients with advanced malignancies

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Late-Breaking Abstracts
Clinical Trial In Progress
1495 A phase 1 multicenter study of the safety and efficacy of the NKG2A targeting antibody S095029 as single agent and in combination with anti-PD1 in patients with advanced malignancies
  1. Anna Spreafico1,
  2. Aung Naing2,
  3. Minal Barve3,
  4. Amita Patnaik4,
  5. Xenophon Ianopulos5,6,
  6. Pauline Drean6,
  7. Agnes Hemon6,
  8. Chahrazade CK Kantari6,
  9. Peng He5,
  10. Vasileios Askoxylakis5,6 and
  11. Nehal Lakhani7
  1. 1Princess Margaret Cancer Center, Toronto, ON, Canada
  2. 2The University of Texas, MD Anderson Cancer Center, Houston, TX, USA
  3. 3Mary Crowley Cancer Center, Dallas, TX, USA
  4. 4The START Center for Cancer Research, San Antonio, TX, USA
  5. 5Servier BioInnovation, Boston, MA, USA
  6. 6Institut de Recherches Internationales Servier, Suresnes, Paris, France
  7. 7START-Midwest, Grand Rapids, MI, USA

  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint are the authors/funders, who have granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

Abstract

Background NKG2A (CD159a) is a C type lectin that heterodimerizes with CD94 creating an inhibitory receptor expressed on immune cells. S095029 is a fully human monoclonal IgG1 anti-NKG2A antibody with attenuated Fc-effector functions that specifically binds the NKG2A/CD94 heterodimer, blocking the interaction with its ligand HLA-E. Sym021 is an anti-PD1 IgG1 antibody. Preclinical data demonstrated that S095029 combined with Sym021 results in enhanced antitumor activity.

Methods This first-in-human, open-label, multicenter study (NCT05162755) evaluates safety, tolerability, preliminary efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of S095029 as monotherapy or combined with Sym021 in patients with advanced solid tumors. Monotherapy regimen included 2doses of S095029 Q2W (one 28-day cycle) followed by single agent Sym021 (Q2W). AEs were defined per CTCAE v5.0. Antitumor activity was evaluated per RECIST 1.1. Exploratory objectives included assessment of cytokine secretion as PD markers and target engagement/receptor occupancy in NKG2A expressing cells in peripheral blood.

Results As of August 19 2024, 21 patients with heavily pretreated solid tumors were treated with S095029 as single agent (10, 30, 100, 300, 750 and 1500mg) and 20 patients were treated with S095029 (30, 100, 300, 750 and 1500mg) in combination with Sym021 (200mg). S095029 was well tolerated without dose-limiting toxicities for both monotherapy and combination with anti-PD1. MTD was not reached. Two patients (9.5%; uterine sarcoma, porocarcinoma) who received one cycle of S095029 monotherapy followed by Sym021 and 2 patients (10%; leiomyosarcoma, squamous cell carcinoma of unknown primary) who received S095029 in combination with Sym021 showed confirmed partial responses. None of these patients had received prior anti-PD1 treatment. The clinical benefit rate (CR+PR+SD≥ 6 months) by RECIST v1.1 in all enrolled patients (n=41) was 19.5%. S095029 serum concentrations increased with dose for both monotherapy and combination with Sym021. Full receptor occupancy was achieved starting at low doses of 30 mg Q2W. Increases in levels of IFNγ, TNFα and CXCL9 in peripheral blood were detected following treatment with S095029. The recommended Phase 2 dose in combination with PD1 blockade was determined at 1140 mg Q3W.

Conclusions The anti-NKG2A antibody S095029 in combination with anti-PD1 Sym021 demonstrated a favorable safety profile and exhibited antitumor activity in unselected, heavily pre-treated patients with advanced malignancies. S095029 is currently investigated in combination with anti-PD1 in patients with previously untreated advanced NSCLC with high PDL1 expression (NCT06162572), and in patients with MSI-H/dMMR advanced gastric/GEJ cancer (NCT06116136).

Acknowledgements This study was sponsored by Servier.

Trial Registration NCT05162755.

Ethics Approval Written informed consent was provided by all the patients or their legal guardians before participation in the trial, and approval from the institutional review board or independent ethics committee was obtained at each trial site.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/jitc-2024-SITC2024.1495

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