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503 Clinical activity of ICT01, an anti-BTN3A-targeted, γ9δ2-activating mAb, alone and in combination with pembrolizumab in patients with advanced/refractory solid tumors: EVICTION trial
  1. Martin Wermke1,
  2. Aurelien Marabelle2,
  3. Christiane Jungels3,
  4. Johann De Bono4,
  5. Norbert Vey5,
  6. Cécile Vicier5,
  7. Elena Garralda6,
  8. Steven Le Gouill7,
  9. Patricia LoRusso8,
  10. Stephane Champiat2,
  11. Catrin List1,
  12. Vladimir Galvaö de Aguiar6,
  13. Katrin Wetzko1,
  14. Leo Rhunke1,
  15. Aude de Gassart9,
  16. Patrick Brune9,
  17. Emmanuel Valentin9,
  18. Marina Iche10,
  19. Daniel Olive11 and
  20. Paul Frohna9
  1. 1Medical Faculty Carl Gustav Carus, Technical University, Dresden, Germany, Dresden, Germany
  2. 2Gustave Roussy, Paris, France, Villejuif, France
  3. 3Institut Jules Bordet, Brussels, Belgium
  4. 4The Institute for Cancer Research and Royal Marsden, London, UK, London, UK
  5. 5Institut Paoli-Calmettes, Marseille, France
  6. 6Vall d’Hebron Institute of Oncology, Barcelona, Spain
  7. 7CHU de Nantes, Nantes, France
  8. 8Yale University Cancer Center, New Haven, USA
  9. 9Imcheck Therapeutics, Marseille, France
  10. 10Ilife consulting, Argenteuil, France
  11. 11CRCM, INSERM U1068, Marseille, France


Background We presented EVICTION Trial data from patients with solid tumors that showed microgram doses of ICT01 rapidly activate γ9δ2 T cells that release inflammatory cytokines (e.g., IFNγ) and traffic from the circulation (Abstract #316, SITC 2020). Confirming tumor infiltration of activated γ9δ2 T cells and the subsequent clinical benefit are the next steps in characterizing the therapeutic potential of ICT01.

Methods EVICTION is an ongoing Phase 1/2a, EU and US trial assessing ICT01 monotherapy (IV Q3W) in advanced/refractory solid and hematologic cancers, and ICT01 in combination with pembrolizumab (200mg IV Q3W) in solid tumor patients who failed ≥1 CPI. Pharmacodynamic activity was monitored by immunophenotyping and cytokine level analysis. Tumor biopsies (baseline, Day 28) were used for immunohistochemistry of BTN3A and tumor-infiltrating lymphocytes, and gene expression profiling. Efficacy evaluations were conducted every 8 weeks.

Results ICT01 monotherapy dose escalation (20µg to 200mg IV ICT01 Q3W) in solid tumor patients (Group A, n=32) has been completed, and 3 dose cohorts of ICT01 (700µg, 2 and 7 mg) plus Pembro (Group C, n=12) were completed; both without any DLTs. First-dose fever and chills (Grade 1/2) were the most common AEs that increased in frequency but not severity with dose and did not recur.ICT01 induced trafficking of >95% of circulating γ9δ2 T cells within 30 min post ICT01 (≥2mg), which was sustained for 21 days at doses ≥75mg. Transient, dose-dependent increases in serum cytokines at 30 min (TNFα) or 4h (IFNγ) post-dose were correlated with baseline γ9δ2 T cell counts and with activation and migration of NK and CD8 T cells out of the blood at doses ≥7mg. Higher baseline circulating γ9δ2 T cells and lower TILs were associated with more robust intra-tumoral increases in total γδ(3–34x increase), CD3 (3–55x increase) and CD8 T cells (1.3–66x increase), which demonstrated the potential to transform an immune desert tumor phenotype. Disease control by ITT analysis of RECIST1.1 data was observed in 6/32 (SD) and 4/7 patients (3 SD (bladder, melanoma, NSCLC), 1 PR (bladder)) in Groups A and C, respectively, with 5/6 patients at 7mg in Group C not yet evaluable.

Conclusions These results show a broad antitumor immune response in the blood and tumors comprising γ9δ2, CD8 T cell, and NK cell activation and tumor-infiltration following ICT01 alone and in combination with pembrolizumab. Preliminary efficacy data suggest low-dose ICT01 plus pembrolizumab may be more effective than ICT01 monotherapy for advanced/refractory solid tumors, which requires confirmation.

Acknowledgements Lena Daher for her medical/scientific writing support.

Trial Registration NCT04243499; EudraCT Number: 2019-003847-31

Ethics Approval This study was approved by the following Ethics Committees: COMITE DE PROTECTION DES PERSONNES, Sud-Méditerranée V (Gustave Roussy, IPC, Nantes), Comité d’Ethique Institut Jules Bordet, COMITÉ DE ÉTICA DE INVESTIGACIÓN CLÍNICA CON MEDICAMENTOS del Hospital Universitari Vall d’Hebron, Ethikkommission an der TU Dresden, HRA London-Surrey Borders Research Ethics Committee.

Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

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