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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Solid Tumor, Adult, Hematopoietic/Lymphoid Cancer

Intervention / Treatment
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* Biological: IV ICT01


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Voluntarily signed informed consent form. 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 Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Life expectancy > 3 months as assessed by the Investigator 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: Any malignancy of Vγ9Vδ2 T cell origin 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) Treatment with investigational drug(s) within 28 days before study treatment 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. 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 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. Within 4 weeks of major surgery Documented history of active autoimmune disorders requiring systemic immunosuppressive therapy within the last 12 months Primary or secondary immune deficiency Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be assigned to a dose level of ICT01 at the time of their enrollment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV ICT01 Monotherapy<br>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<br>* humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody<br>|
| Experimental: IV ICT01 + IV Pembrolizumab<br>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<br>* humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gamma delta T cells, butyrophilin, pembrolizumab