Relapsed/refractory solid tumors or hematological cancers MedDRA version: 21.1 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: ICT01
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ICT01
Current Sponsor code: ict01
Other descriptive name: ICT01
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
ImCheck Therapeutics
Eligibility
Sex/Gender
All
Inclusion criteria
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) Patients with histologically or cytologically confirmed diagnosis of advanced cancer including: a. Group A: Relapsed/refractory advanced bladder, breast, colorectal, gastric, ovarian, or prostate cancer, melanoma, or PDAC; b. Group B: Relapsed/refractory advanced hematologic malignancies including AML, acute lymphocytic leukemia, diffuse large B cell lymphoma, and follicular lymphoma; c. Group C: Relapsed/refractory advanced bladder cancer, HNSCC, melanoma, or non-small cell lung cancer (approved indications in US and EU for pembrolizumab); d.Group D: persistent or recurrent advanced epithelial ovarian cancer, primary fallopian or primary peritoneal cancer, treated with at least 1 prior systemic platinum-containing regimen and that progressed within 6 months of the end of the most recent systemic platinum-containing regimen; e.Group E: mCRPC in patients who failed prior androgen deprivation therapy. Patients may have also failed prior taxane therapy; f.Group F: Newly diagnosed AML, by WHO 2022 criteria, in patients who are indicated to start treatment with VEN/AZA g. Group G: metastatic or unresectable melanoma with primary resistance following at least 6 weeks of prior CPI treatment for advanced disease, h.Group H: locally advanced or metastatic urothelial carcinoma i.Group I: metastatic or unresectable, recurrent HNSCC 4) Willingness to undergo Screening, baseline, and on-study tumor biopsies or BMAs, as applicable; 5) Eastern Cooperative Oncology Group (ECOG) performance status = 1 6) Life expectancy > 3 months as assessed by the Investigator 7)All groups except Group F,Clinical labs: a. Hematology: - Hemoglobin =8.5 g/dL (equal to 5.28 mmol/L; transfusion dependent or independent); - All groups except Group B and F: • platelet count =75 × 109/L; • lymphocyte count =0.5 × 109/L; • absolute neutrophil count =1.0 × 109/L; b. Liver enzymes: - AST and 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 (i.e., a method with less than 1% failure rate [e.g., sterilization, hormone implants, hormone injections, some intrauterine devices, sexual abstinence, or vasectomized partner]) consistently and correctly during the study and for at least 5 months after the last dose of any 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 any 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 anystudy drug ii.agree to not donate sperm during t
Exclusion criteria
Exclusion criteria: 1) Any malignancy of ?9d2 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 initiation (does not apply to patients receiving pembrolizumab in the combination arms); 3)Treatment with investigational drugs within 28 days before study treatment initiation 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-mediated adverse events (imAEs) and/or adverse events (AEs) Grade =2 from previous therapies, except for vitiligo, stable Grade 2 neuropathy, 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).Patients positive for HIV can be eligible if cluster of differentiation (CD)4+ T-cell counts =350 cells and have no history of AIDS-defining opportunistic infections in the past 12 months, as deemed appropriate by the Investigator; 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. Part 2 Group F, all above apply with following additions aligned with Viale-A trial 18)Patients with t(15;17), t(8;21), inv(16), or t(16;16) karyotypic abnormality; 19)Patient has history of myeloproliferative neoplasm including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation; 20)Patient has a white blood cell count >25 x 10?/L. In the EU and UK: hydroxyurea, and/or cytarabine (up to 1 g total) is permitted to meet this criterion. In the US: hydroxyurea, leukapheresis, or cytarabine (low dose, e.g., 20 mg twice daily) is permitted to meet this criterion. 21)Patients with known symptomatic or uncontrolled central nervous system leukemia; 22)Any previous or concomitant malignancy, except when the patient has completed definitive curative-intent t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part 1 Characterize the safety and tolerability of ICT01 intravenous (IV) as monotherapy, and in combination with pembrolizumab (Keytruda®) in patients with relapsed/refractory advanced solid tumors or hematologic malignancies. Part 2 Characterize the preliminary anti-tumor activity of ICT01 IV as monotherapy and in combination with pembrolizumab in patients with relapsed/refractory advanced solid tumors and in combination with venetoclax (VEN; Venclyxto®, Venclexta®)/ azacitidine (AZA; Vidaza®) in with newly diagnosed acute myeloid leukemia (AML);Secondary Objective: Part 1 1. Determine the recommended ICT01 dose(s) for use as monotherapy and in combination with pembrolizumab. 2. Characterize the pharmacokinetics (PK) of IV ICT01 administered 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. Determine the recommended ICT01 dose(s) for use in combination with VEN/AZA. 2. Characterize the overall safety and tolerability of IV ICT01 as monotherapy, and in combination with pembrolizumab or VEN/AZA 3.Characterize the PK of IV ICT01 administered as monotherapy and in combination with pembrolizumab or VEN/AZA. ;Primary end point(s): Part 1: Incidence, severity (according to National Cancer Institute [NCI]- Common Terminology Criteria for Adverse Events [CTCAE] Version 5), and relationship to study treatment of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and TEAEs leading to discontinuation of study treatment or treatment modifications; • Incidence and severity (according to NCI-CTCAE Version 5) of clinical laboratory abnormalities; • Clinically significant findings on vital signs, electrocardiograms (ECGs), and physical examinations. Part 2: • DCR according to RECIST Versi | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part 1: -Incidence of dose-limiting toxicities (DLTs), other safety measures, and biomarker data. -PK parameters of ICT01, including maximum serum drug concentration (Cmax), area under the concentration-time curve (AUC), elimination half-life (t1/2), clearance. -Disease control rate (DCR) and objective response rate (ORR) according to Response Evaluation Criteria In Solid Tumors (RECIST), immunotherapy RECIST (iRECIST), Response Evaluation Criteria In Lymphoma (RECIL), or as per disease-specific standards in other hematologic indications, as appropriate. Part 2: -Incidence of DLTs, other safety measures, and biomarker data. -Incidence, severity (according to CTCAE Version 5), and relationship of TEAEs, SAEs, and TEAEs leading to discontinuation of study treatment or treatment modifications; -Incidence and severity (according to CTCAE Version 5) of clinical laboratory abnormalities; -Clinically significant findings on vital signs, ECGs, and physical examinations. -PK parameters of ICT01, including Cmax, AUC, t1/2, and clearance.;Timepoint(s) of evaluation of this end point: On-going throughout the duration of the study | — |
Countries
Belgium, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactChief Medical Officer
ImCheck Therapeutics
Outcome results
None listed