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

• ClinicalTrials.gov Identifier: NCT04243499
• Recruitment Status: Recruiting
• First Posted: January 28, 2020
• Last Update Posted: December 29, 2023
• Sponsor: ImCheck Therapeutics
• Information provided by (Responsible Party): ImCheck Therapeutics

Tracking Information

• First Submitted Date: January 24, 2020
• First Posted Date: January 28, 2020
• Last Update Posted Date: December 29, 2023
• Actual Study Start Date: February 10, 2020
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 5, 2022)

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

Original Primary Outcome Measures (submitted: January 24, 2020)

• Adverse Events (Parts 1 & 2) [ Time Frame: 6 months ]
  Incidence of treatment-emergent adverse events
• Objective Response Rate using RECIST for solid tumor patients (Part 2) [ Time Frame: 6 months ]
  RECIST is measured every 8 weeks during treatment
• Objective Response Rate using RECIL for lymphoma patients (Part 2) [ Time Frame: 6 months ]
  RECIL is measured every 8 weeks during treatment

Current Secondary Outcome Measures (submitted: October 5, 2022)

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

Original Secondary Outcome Measures (submitted: January 24, 2020)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: First-in-Human Study of ICT01 in Patients With Advanced Cancer
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients will be assigned to a dose level of ICT01 at the time of their enrollment

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Solid Tumor, Adult
• Hematopoietic/Lymphoid Cancer

Intervention

Biological: IV ICT01

humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody

Study Arms

• 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
  Intervention: Biological: IV ICT01
• 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
  Intervention: Biological: IV ICT01

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 24, 2020): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Paul Frohna, MD, PhD; 8582055285; paul.frohna@imcheck.fr

• Listed Location Countries: Belgium, France, Germany, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04243499
• Other Study ID Numbers: ICT01-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: ImCheck Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: ImCheck Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Paul Frohna, MD, PhD; ImCheck Therapeutics

• PRS Account: ImCheck Therapeutics
• Verification Date: December 2023