Hematopoietic/Lymphoid Cancer, Solid Tumor, Adult
Conditions
Keywords
gamma delta T cells, butyrophilin, pembrolizumab
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.
Interventions
BIOLOGICALIV ICT01
humanized anti-Butyrophilin 3A (BTN3A) monoclonal antibody
Sponsors
ImCheck Therapeutics, an Ipsen company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients will be assigned to a dose level of ICT01 at the time of their enrollment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with TEAES leading to discontinuation of study treatment or treatment modifications (Part 1) | From baseline to at least 6 months | Treatment emergent adverse events (TEAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0. |
| Percentage of participants with SAEs (Part 1) | From baseline to at least 6 months | Serious Adverse Events (SAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0 |
| Percentage of participants with clinically significant change from baseline clinical laboratory abnormalities (Part 1) | From baseline to at least 6 months | With severity measured according to NCI-CTCAE Version 5.0 |
| Percentage of participants with clinically significant change from baseline vital sign readings (Part 1) | From baseline to at least 6 months | Vital signs will be assessed by the investigators for clinical significance. |
| Percentage of participants with clinically significant change from baseline in 12-lead Electrocardiogram (ECG) readings (Part 1) | From baseline to at least 6 months | 12-lead (echocardiogram) ECGs will be assessed by the investigators for clinical significance. |
| Percentage of participants with clinically significant change from baseline physical examinations (Part 1) | From baseline to at least 6 months | Physical examinations will be assessed by the investigators for clinical significance. |
| Duration of Complete Response (DCR) (Part 2) | From baseline to at least 6 months | DCR according to RECIST Version 1.1 for all groups except Group F (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\]); |
| Percentage of participants with TEAES (Part 1) | From baseline to at least 6 months | Treatment emergent adverse events (TEAEs) with severity according to National Cancer Institute \[NCI\]- Common Terminology Criteria for Adverse Events \[CTCAE\] Version 5.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax following the first dose of ICT01 | 1 day | PK parameter from serum ICT01 levels |
| AUC following the first dose of ICT01 | 21 days | PK parameter from serum ICT01 levels |
| Clearance at steady-state of ICT01 | 6 months | PK parameter from serum ICT01 levels |
| Half-life 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 |
| Change from Baseline in the Number of Circulating Gamma Delta T Cells | 28 days | Flow cytometric counting of circulating gamma delta T cells |
Countries
Belgium, France, Germany, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed