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.
Brief Title
First-in-Human Study of ICT01 in Patients With Advanced Cancer
Completion Date
Completion Date Type
Estimated
Conditions
Solid Tumor, Adult
Hematopoietic/Lymphoid Cancer
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
gamma delta T cells
butyrophilin
pembrolizumab
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04243499
Org Class
Industry
Org Full Name
ImCheck Therapeutics
Org Study Id
ICT01-101
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Description
Incidence of treatment-emergent adverse events
Outcome Measure
Adverse Events (Parts 1 & 2)
Outcome Time Frame
12 months
Outcome Description
RECIST is measured every 8 weeks during treatment
Outcome Measure
Disease Control Rate using RECIST for solid tumor patients (Part 2)
Outcome Time Frame
12 months
Outcome Description
RECIL is measured every 8 weeks during treatment
Outcome Measure
Disease Control Rate using RECIL for lymphoma patients (Part 2)
Outcome Time Frame
12 months
Secondary Outcomes
Outcome Description
Flow cytometric counting of circulating gamma delta T cells
Outcome Time Frame
28 days
Outcome Measure
Change from Baseline in the Number of Circulating Gamma Delta T Cells
Outcome Description
Flow cytometric measurement of CD69 and Ki67 expression on gamma delta T cells
Outcome Time Frame
28 days
Outcome Measure
Change from Baseline in the Activation State of Circulating Gamma Delta T Cells
Outcome Description
PK parameter from serum ICT01 levels
Outcome Time Frame
1 day
Outcome Measure
Cmax following the first dose of ICT01
Outcome Description
PK parameter from serum ICT01 levels
Outcome Time Frame
21 days
Outcome Measure
AUC following the first dose of ICT01
Outcome Description
PK parameter from serum ICT01 levels
Outcome Time Frame
6 months
Outcome Measure
Clearance at steady-state of ICT01
Outcome Description
PK parameter from serum ICT01 levels
Outcome Time Frame
6 months
Outcome Measure
Half-life of ICT01
Outcome Description
RECIST is measured every 8 weeks during treatment
Outcome Time Frame
12 months
Outcome Measure
Objective Response Rate using RECIST for solid tumor patients (Part 2)
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18