First-in-Human Study of ICT01 in Patients with Advanced Cancer

Phase 1

Active, not recruiting

• Conditions: Solid Tumor, Adult; Hematopoietic/Lymphoid Cancer
• Interventions: Biological: IV ICT01

• Registration Number: NCT04243499
• Lead Sponsor: ImCheck Therapeutics

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 available

Study Timeline

• Study First Submitted: 2020-01-24
• Study First Submitted QC: 2020-01-24
• Study First Posted: 2020-01-28
• Study Start: 2020-02-10
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-28
• Primary Completion: 2025-09
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 292

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IV ICT01 Monotherapy	IV ICT01	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
IV ICT01 + IV Pembrolizumab	IV ICT01	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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (29)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

City of Hope Comprehensive Cancer Center; 🇺🇸 Duarte, California, United States

H. Lee Moffitt Cancer Center and Research Institute; 🇺🇸 Tampa, Florida, United States

Montefiore Medical Center; 🇺🇸 Bronx, New York, United States

US Oncology Research; 🇺🇸 Irving, Texas, United States

Institut Bergonie; 🇫🇷 Bordeaux, France

Haut Leveque; 🇫🇷 Bordeaux, France

Centre Hospitalier Lyon Sud; 🇫🇷 Lyon, France

Centre Lyon Berard; 🇫🇷 Lyon, France

CHU Lyon; 🇫🇷 Lyon, France

CHU Nantes; 🇫🇷 Nantes, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Pitie-Salpetriere; 🇫🇷 Paris, France

Institut Curie; 🇫🇷 Paris, France

CHU Poitiers; 🇫🇷 Poitiers, France

universitatklinikum Wurburg; 🇩🇪 Wurzburg, Germany

START Barcelone HM Nou Delfos; 🇪🇸 Barcelona, Spain

START Madrid-FJD, Hospital Fundación Jiménez Díaz; 🇪🇸 Madrid, Spain

Hospital Universitario HM Sanchinarro; 🇪🇸 Madrid, Spain

NHS Greater Glasgow and Clyde, Beatson West of Scotland Cancer Centre; 🇬🇧 Glosgow, United Kingdom

Yale Cancer Center; 🇺🇸 New Haven, Connecticut, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Institut Jules Bordet; 🇧🇪 Brussels, Belgium

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Gustave Roussy; 🇫🇷 Paris, France

University Carl Gustav Carus Clinical Trial Unit; 🇩🇪 Dresden, Germany

Vall d'Hebron Instiute of Oncology; 🇪🇸 Barcelona, Spain

Institute of Cancer Research; 🇬🇧 London, United Kingdom