First-in-Human Study of ICT01 in Patients With Advanced Cancer (EVICTION)

A First-in-human, Two-part Clinical Study to Assess the Safety, Tolerability and Activity of IV Doses of ICT01 as Monotherapy and in Combination With a Checkpoint Inhibitor, in Patients With Advanced-stage, Relapsed/Refractory Cancer

Part 1 will be a dose escalation study of IV ICT01 (a monoclonal antibody targeting BTN3A) as monotherapy in patients with advanced solid or hematologic tumors, followed by a cohort examining the combination of ICT01 plus pembrolizumab (Keytruda). Part 2 will be a cohort expansion into 2 solid tumor indications and one hematologic malignancy for ICT01 monotherapy, and 3 solid tumor indications for the combination of ICT01 plus pembrolizumab.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic/Lymphoid Cancer; Solid Tumor, Adult
• Intervention / Treatment: Biological: IV ICT01

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Paul Frohna, MD, PhD; Phone Number: 8582055285; Email: paul.frohna@imcheck.fr

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Institut Jules Bordet
    • Principal Investigator: Christiane Jungels, MD
    • Contact: Joanna Neto; Email: joana.neto@bordet.be
• France
  • Marseille, France
    • Recruiting
    • Institut Paoli-Calmettes
    • Principal Investigator: Norbert Vey, MD
    • Contact: Julie Karsenty; Email: KARSENTYJ@ipc.unicancer.fr
  • Paris, France
    • Recruiting
    • Gustave Roussy
    • Contact: Manare ALI; Email: Manare.ALI@gustaveroussy.fr
    • Principal Investigator: Aurelien Marabelle, MD, PhD
• Germany
  • Dresden, Germany
    • Recruiting
    • University Carl Gustav Carus Clinical Trial Unit
    • Principal Investigator: Martin Wermke, MD
    • Contact: Sophia Tischer; Email: Sophia.Tischer@uniklinikum-dresden.de
• Spain
  • Barcelona, Spain
    • Recruiting
    • Vall d'Hebron Instiute of Oncology
    • Contact: Nuria Farras LLansana; Email: nfarras@vhio.net
    • Principal Investigator: Elena Garralda, MD
• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Institute of Cancer Research
    • Contact: Robert Daly; Email: robert.daly@icr.ac.uk
    • Principal Investigator: Johann de Bono, MD, PhD
• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale Cancer Center
      • Contact: Priscilla Steve; Email: priscilla.steve@yale.edu
      • Principal Investigator: Patricia LoRusso, DO,
  • Texas
    • Houston, Texas, United States, 77030
      • Not yet recruiting
      • The University Of Texas MD Anderson Cancer Center
      • Contact: Carissa Jurisprudencia; Email: CGjurisprudencia@mdanderson.org
      • Principal Investigator: Abishek Maiti, MD
  • Washington
    • Seattle, Washington, United States, 98133
      • Recruiting
      • University of Washington
      • Principal Investigator: Evan Hall, MD
      • Contact: Amanda Ramsing-Lund; Email: aramsing@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily signed informed consent form.

2. Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer, including:

   Group A: bladder, breast, colon, gastric, melanoma, ovarian, prostate and PDAC Group B: hematologic malignancies including acute myeloid leukemia, acute lymphocytic leukemia, Diffuse large B cell lymphoma and follicular lymphoma Group C: melanoma, cervical, bladder, gastric, head and neck SCC, and lymphoma (according to the approved package labeling of the ICI) Part 2, Group D: Ovarian cancer (2L/3L) with baseline g9d2 T cells > 20K Part 2, Group E: metastatic castrate resistant prostate cancer (2L/3L) with baseline g9d2 T cells > 20K Part 2, Group F: newly diagnosed AML starting venetoclax/azacitidine Part 2, Group G: checkpoint-refractory metastatic melanoma with g9d2 T cells >5K Part 2, Group H: chemotx-refractory or Pt-ineligible urotherlial cancer (bladder) with g9d2 T cells >5K Part 2, Group I: checkpoint-refractory, metastatic HNSCC with g9d2 T cells >5K

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 Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts

Exclusion Criteria:

1. Any malignancy of Vγ9Vδ2 T cell origin
2. Any anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment (does not apply to patients receiving ICI for the combination arm)
3. Treatment with investigational drug(s) 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 need for ongoing treatment.
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) and/or AEs ≥grade 2 not resolved from previous therapies except vitiligo, stable neuropathy up to grade 2, hair loss, and stable endocrinopathies with replacement hormone therapy.
7. Within 4 weeks of major surgery
8. Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy within the last 12 months
9. Primary or secondary immune deficiency
10. Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IV ICT01 Monotherapy; Up to six ICT01 dose levels administered as IV monotherapy every 3 weeks will be tested in Part 1 Dose Escalation and up to 2 dose levels in Part 2 Cohort Expansion	Biological: IV ICT01; humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody
Experimental: IV ICT01 + IV Pembrolizumab; A range of IV ICT01 doses administered every 3 weeks will be tested in combination with 200 mg pembrolizumab in Part 1 Dose Escalation and up to 2 dose levels of ICT01 plus 200 mg pembrolizumab in Part 2 Cohort Expansion	Biological: IV ICT01; humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (Parts 1 & 2)	Incidence of treatment-emergent adverse events	12 months
Disease Control Rate using RECIST for solid tumor patients (Part 2)	RECIST is measured every 8 weeks during treatment	12 months
Disease Control Rate using RECIL for lymphoma patients (Part 2)	RECIL is measured every 8 weeks during treatment	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in the Number of Circulating Gamma Delta T Cells	Flow cytometric counting of circulating gamma delta T cells	28 days
Change from Baseline in the Activation State of Circulating Gamma Delta T Cells	Flow cytometric measurement of CD69 and Ki67 expression on gamma delta T cells	28 days
Cmax following the first dose of ICT01	PK parameter from serum ICT01 levels	1 day
AUC following the first dose of ICT01	PK parameter from serum ICT01 levels	21 days
Clearance at steady-state of ICT01	PK parameter from serum ICT01 levels	6 months
Half-life of ICT01	PK parameter from serum ICT01 levels	6 months
Objective Response Rate using RECIST for solid tumor patients (Part 2)	RECIST is measured every 8 weeks during treatment	12 months

Collaborators and Investigators

• Sponsor: ImCheck Therapeutics
• Investigators: Study Director: Paul Frohna, MD, PhD, ImCheck Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: January 24, 2020
• First Submitted That Met QC Criteria: January 24, 2020
• First Posted (Actual): January 28, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2023
• Last Update Submitted That Met QC Criteria: December 28, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: pembrolizumab; gamma delta T cells; butyrophilin
• Other Study ID Numbers: ICT01-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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