Phase 1/2a Study of ICT01 Plus Low Dose SC IL-2 in Patients With Advanced Solid Tumors (EVICTION-2)

A Two-part, Open-label, Clinical Study to Assess the Safety, Tolerability and Activity of Intravenous Doses of ICT01 in Combination With Low-dose Subcutaneous Interleukin-2 in Patients With Advanced Solid Tumors (EVICTION-2)

This is a phase I/IIa, two-part, open-label study to characterize the safety, tolerability, pharmacodynamics, and antitumor activity of ICT01 in combination with LDSC IL-2 in patients with advanced-stage solid tumors.

Part 1 will be a dose escalation of IV ICT01 administered on the first day of every 21-day cycle (CnD1) to patients with advanced-stage solid tumors in combination with LDSC IL-2 (Proleukin®) administered daily on days 1-5 of cycles 1-3 (C1-3D1-5). Objectives of part 1 are to characterize the safety of the combination regimen and determine the RP2D for Part 2.

Part 2 will comprise a maximum of 2 indications and 2 combination dosing regimens of ICT01 +LDSC IL-2, which will be supported by statistical power calculations once the indications are selected. The final regimen will be ICT01 + LDSC IL-2 + Pembrolizumab on a Q3W cycle. The primary objective of Part 2 is to demonstrate the efficacy of the combination regimen based on RECIST1.1 in one or more solid tumor indications.

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor, Adult
• Intervention / Treatment: Drug: ICT01; Drug: Proleukin Injectable Product; Drug: Pembrolizumab injection

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Paul Frohna, MD, PhD; Phone Number: +33698465644; Email: paul.frohna@imcheck.fr

Study Locations

• France
  • Paris, France
    • Recruiting
    • Institute Gustave Roussy
    • Contact: Stephane Champiat, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Relapsed/refractory patients who have failed at least 2 lines of systemic therapy or who failed first line therapy and are intolerant of or have a contraindication to the standard second line of therapy with histologically or cytologically confirmed diagnosis of:

   1. metastatic colorectal cancer (CRC):
   2. metastatic ovarian cancer:
   3. metastatic castration-resistant prostate cancer (mCRPC)

   4. metastatic pancreatic ductal adenocarcinoma (PDAC)

      2) Willingness to undergo baseline and on-study tumor biopsies 3) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 4) Life expectancy > 3 months as assessed by the Investigator 5) At least 1 measurable lesion per RECIST1.1

      Exclusion Criteria:

      1. 1) Any malignancy of γ9δ2 T cell origin
      2. Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment
      3. Treatment with investigational drugs within 28 days before study treatment
      4. Systemic steroids at a daily dose of > 10 mg of prednisone, > 2 mg of dexamethasone or equivalent, for the last 28 days and ongoing
      5. Patients with rapidly progressing disease defined as advanced/metastatic, symptomatic, visceral spread, with a risk of life-threatening complications in the short term (e.g., during Screening Period/ treatment washout) that includes patients with massive uncontrolled effusions pleural, pericardial, peritoneal, pulmonary lymphangitis, and over 50% liver involvement
      6. Ongoing immune-related adverse events (irAEs) ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with substitutive hormone therapy.
      7. Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy
      8. Primary or secondary immune deficiency
      9. Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment
      10. Patients with contraindication to IL-2 treatment according to the SmPC/package insert

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose level 2 ICT01 + Low dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2
Experimental: Dose Level 1 ICT01 + High dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2
Experimental: Dose level 3 ICT01 + Low dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2
Experimental: Dose level 4 ICT01 + Low dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2
Experimental: Part 2 ICT01 + Low dose SC IL-2 + Pembrolizumab; The best regimen of ICT01+IL-2 will be combined with pembrolizumab at the approved dose since the combination of ICT01+IL-2 induces upregulation of PD-1 on g9d2 T cells and in the TME.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2; Drug: Pembrolizumab injection; 200mg administered following ICT01 + LDSC IL-2 over 30 min Q3W
Experimental: Dose level 1 ICT01 + Low dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2
Experimental: Dose level 5 ICT01 + Low dose SC IL-2; For all arms, ICT01 IV is given on Day 1 of every 21-day cycle. SC IL-2 is administered Days 1-5 of cycles 1/2/3 only.	Drug: ICT01; anti-BTN3A mAb IV Q3W; Drug: Proleukin Injectable Product; 1 MIU/m2 SC IL-2 daily x 5 days for the first 3 cycles; Other Names: IL-2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-Emergent Adverse Events	Incidence and severity of adverse events related to study treatment	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the number of circulating g9d2 T cells	flow cytometry measurement of circulating and intratumoral g9d2 T cells	Cycle Days 8 & 15 for the first 3 cycles
Disease Control Rate	Stable disease or better by RECIST1.1	1 year

Collaborators and Investigators

• Sponsor: ImCheck Therapeutics
• Collaborators: ILife Consulting; Exystat
• Investigators: Study Director: Paul Frohna, MD, PhD, ImCheck Therapeutics

Publications and helpful links

General Publications

• De Gassart A, Le KS, Brune P, Agaugue S, Sims J, Goubard A, Castellano R, Joalland N, Scotet E, Collette Y, Valentin E, Ghigo C, Pasero C, Colazet M, Guillen J, Cano CE, Marabelle A, De Bonno J, Hoet R, Truneh A, Olive D, Frohna P. Development of ICT01, a first-in-class, anti-BTN3A antibody for activating Vgamma9Vdelta2 T cell-mediated antitumor immune response. Sci Transl Med. 2021 Oct 20;13(616):eabj0835. doi: 10.1126/scitranslmed.abj0835. Epub 2021 Oct 20.

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 24, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2023
• Last Update Submitted That Met QC Criteria: August 17, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Aldesleukin; Pembrolizumab
• Other Study ID Numbers: ICT01-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No