E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory solid tumors or hematological cancers |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed/refractory solid tumors or hematological cancers |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065147 |
E.1.2 | Term | Malignant solid tumor |
E.1.2 | System Organ Class | 100000004864 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066481 |
E.1.2 | Term | Hematological malignancy |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1 Characterize the overall safety and tolerability profile of a range of intravenous (IV) doses of ICT01 as monotherapy, and in combination with pembrolizumab in patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers. Part 2 Characterize the preliminary anti-tumor activity of IV ICT01 as monotherapy and in combination with pembrolizumab in patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers. |
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E.2.2 | Secondary objectives of the trial |
Part 1 1. Characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of IV ICT01 administered to patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers 2. Determine the recommended dose(s) for the expansion cohorts (Part2) for ICT01 as monotherapy and in combination with pembrolizumab 3. Characterize the preliminary anti-tumor activity of a range of IV doses of ICT01 as monotherapy and in combination with pembrolizumab when administered to patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers
Part 2 1. Characterize the overall safety and tolerability of IV ICT01 as monotherapy, and in combination with pembrolizumab in patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers. 2. Characterize the PK and PD of IV ICT01 administered to patients with advanced-stage, relapsed/refractory solid tumors or hematologic cancers. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
The following criteria must be checked over the screening period and at baseline. ALL inclusion criteria must be met to include the subject in the study: Part1: 1) Male or female aged ≥18 years 2) Voluntarily signed written informed consent before performance of any study-related screening procedures 3) Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer including: a. Group A: bladder, breast, colorectal, gastric, melanoma, ovarian, prostate and PDAC b. Group B: hematologic malignancies including acute myeloid leukemia, acute lymphocytic leukemia, Diffuse large B cell lymphoma and follicular lymphoma c. Group C: melanoma, bladder, head and neck SCC, and non small cell lung cancer (approved indications in the US & EU for pembrolizumab) 4) Willingness to undergo baseline and on-study tumor biopsies 5) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 6) Life expectancy > 3 months as assessed by the Investigator 7)Clinical labs: a. Hematology: - Hemoglobin ≥8.5 g/dL (equal to 5.28 mmol/L; transfusion dependent or independent); - Group A/C only: • platelet count ≥75 × 109/L; • lymphocyte count ≥0.5 × 109/L; • absolute neutrophil count ≥1.0 × 109/L; b. Liver enzymes: - aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 × upper limit of normal (ULN) (<5 × ULN in the case of liver metastases); - bilirubin ≤1.5 × ULN (<2 × ULN in case of liver metastases); c. Renal function: serum creatinine <1.5 × ULN or creatinine clearance ≥ 50 mL/min (Cockcroft and Gault) for serum creatinine ≥1.5x ULN. 8) Contraceptives measures: a.Women of childbearing potential must: i.have a negative pregnancy test within 1 week before first dose of study drug ii.use highly effective method(s) of birth control consistently and correctly during the study and for at least 5 months after the last dose of study drug iii.agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 5 months after the last dose of study iv.agree to no plan to breastfeed and no plan to become pregnant during the study and for at least 5 months after the last dose of study drug. b.Males who are sexually active must: i.agree to use a condom with spermicidal foam/gel/film/cream/suppository during the study and for at least 5 months after the last dose of study drug ii.agree to not donate sperm during the study and for at least 5 months after the last dose of study drug iii.no plan to father a child during the study or within 5 months after the last dose of study drug. 9) Women must not be breastfeeding 10) At least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST)/ Response Evaluation Criteria in Lymphoma (RECIL) or >5% marrow blasts 11) Patients must have no available standard of care for their disease, as determined by the treating Investigator 12) Patients in the ICT01 Combination arms must meet the eligibility criteria in the approved package labeling of pembrolizumab and meet the following conditions: a. Must not be first-line patients (i.e., must meet Inclusion Criteria #11) b. Must not have any history or ongoing interstitial lung disease c. Must not have undergone prior anterior organ transplantation, including allograft stem cell transplantation
For Part 2, Group D and E: 13) Replaces inclusion criterion # 3: Relapsed/refractory patients with histologically or cytologically confirmed diagnosis of advanced-stage or recurrent cancer including: a. Group D: persistent or recurrent epithelial ovarian cancer, primary fallopian or primary peritoneal cancer; failed at least 1 prior systemic platinum-containing regimen b. Group E: metastatic or unresectable, recurrent HNSCC; failed at least 1 prior systemic regimen 14) Replaces inclusion criterion #11: Patients must have received at least one line of treatment for their cancer prior to enrolling on the study 15) Circulating g9d2 T cell count ≥ 20 000 cells/mL of blood during screening
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E.4 | Principal exclusion criteria |
The following criteria must be checked over the screening period and at baseline. If ANY exclusion criterion applies, the subject must not be included in the study: 1) Any malignancy of γ9δ2 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 pembrolizumab for the combination arms) 3) Treatment with investigational drugs 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 ongoing 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 substitutive 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 11) Known/suspected hypersensitivity against ICT01, human or humanized IgGs, PD-1/PD-L1 blockers or their ingredients 12) Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) 13) Clinically significant cardiac disease including heart failure (New York Heart Association, Class III or IV), pre-existing arrhythmia, uncontrolled angina pectoris, or myocardial infarction within 1 year before study entry 14) Dementia or altered mental status that would prohibit informed consent 15) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator 16) Active drug or alcohol abuse as assessed by the Investigator 17) Patients with uncontrolled and symptomatic brain metastases. Patient with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 4 weeks.
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1. The primary endpoint of safety and tolerability will be evaluated in this study by the incidence, severity, and relationship of TEAEs, SAEs, TEAEs leading to discontinuation of study treatment; and clinically significant findings on clinical laboratory tests, vital signs, ECGs, and physical examinations (Key secondary endpoint in Part 2).
Part 2. Disease Control Rate (DCR) that includes clinical response criteria as per RECIST, RECIL or as per disease-specific standards criteria as per RECIST, RECIL or as per disease-specific standards for the recovery (CRi) + Partial Response/Remission (PR) + Stable Disease.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On-going throughout the duration of the study |
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E.5.2 | Secondary end point(s) |
In Parts 1 and 2, the PK parameters of ICT01 (including Cmax, AUC, t1/2, clearance) will be calculated by dose level. Likewise, the PD activity of ICT01 (by dose and patient population) will include the change from baseline in counts and activation status of Vγ9Vδ2 T cells and other immune cells in the peripheral blood, peripheral blood mononuclear cells (PBMCs) and tumor biopsies, circulating cytokine levels (including IFN gamma, TNF alpha, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL- 10, IL-17a and MCP-1), and expression of PD-L1, PD-1 and other immune cell markers in tumor biopsies and PBMCs.
Baseline BTN3A expression and gamma delta T cells from tumor biopsies, and baseline gamma delta T cells and BTN3A expression in the circulation will be characterized and used as covariates for the PD and clinical response analyses to determine if they have utility for selecting patients for Part 2, future studies and as part of the potential companion diagnostic strategy.
The primary PD activity measure to determine an active dose level of ICT01 will be a decrease from baseline and an increase in activation of circulating gamma delta T cells, as measured by flow cytometry. In Part 1 the preliminary anti-tumor activity endpoint will be the DCR and ORR as per RECIST, RECIL or as per disease-specific standards in the hematologic indications (e.g., Cheson/IWG Criteria for AML). The immunotherapy Response Evaluation Criteria In Solid Tumors (iRECIST (will be considered exploratory.
In Part 2, key secondary endpoints include the safety and tolerability, time to progression (TTP),progression-free survival (PFS) and ORR as per RECIST, RECIL or as per disease-specific standards for the hematologic malignancies (e.g., Cheson/IWG Criteria for AML). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
On-going throughout the duration of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
France |
Germany |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 2 |