Relapsed/refractory patients with advanced solid tumors : metastatic colorectal cancer (CRC) or metastatic ovarian cancer or metastatic castration-resistant prostate cancer (mCRPC) or metastatic pancreatic ductal adenocarcinoma (PDAC). Metastatic or unresectable refractory melanoma MedDRA version: 27.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 27.0
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/l milligram(s)/litre
Concentr
Sponsors
ImCheck Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Part 1 The following criteria must be checked during the screening period and at baseline. ALL inclusion criteria must be met to include the subject in the study: 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 who have failed at least 2 lines of systemic therapy or who failed first line therapy and are intolerant of or have a contraindication to the standard second line of therapy with histologically or cytologically confirmed diagnosis of: a. metastatic colorectal cancer (CRC) i. patients must have progressed after receiv-ing fluoropyrimidine, oxaliplatin, and iri-notecan and an antiangiogenic agent. ii. patients with tumors known to be MSI-H, prior therapy with a checkpoint inhibitor is required if they were clinically able to re-ceive it. iii. patients with epidermal growth factor re-ceptor (EGFR)-expressing, RAS wild-type should have received anti EGFR therapy. b. metastatic ovarian cancer i. patients must be platinum resistant and must have had at least one treatment line after being resistant to platinum chemo-therapy c. metastatic castration-resistant prostate cancer (mCRPC) d. metastatic pancreatic ductal adenocarcinoma (PDAC) e. metastatic or unresectable refractory melanoma with primary resistance following at least 6 weeks of prior CPI treatment, defined as best response of progressive disease or SD of short duration (lasting less than 6 months), as per Society for Immunotherapy of Cancer [SITC] Immunotherapy Resistance Taskforce. Melanoma patients who have proto-oncogene B Raf (BRAF) V600E or V600K mutations must have received prior combination BRAF and mitogen-activated protein kinase (MEK) inhibitor therapy unless they have contraindications, as determined by the treating Investigator. 4) Availability of baseline tumor biopsy and willingness to undergo 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); - platelet count =100 × 109/L; - lymphocyte count =0.5 × 109/L; - absolute neutrophil count =1.0 × 109/L; - White Blood Count (WBC) = 4 × 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) Pulse oximetry of 95% or higher at rest, unless patient has chronic lung disease where 90% or higher at rest is acceptable 9) 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 4 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 4 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 4 months after the last dose of study drug. b. Males must: i. agree to use a c
Exclusion criteria
Exclusion criteria: The following criteria must be checked during the screening period and at baseline. If ANY exclusion criterion applies, the subject must not be included in the study: 1) Any malignancy of ?9d2 T cell origin 2) Any systemic anti-tumor-directed drug therapy within 28 days or 5 times the elimination half-life (whichever is shorter) before study treatment 3) Treatment with investigational drugs within 28 days before study treatment , or 5 half-lives 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) =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) Ongoing systemic autoimmune disease requiring systemic immunosuppressive therapy 8) Primary or secondary immune deficiency 9) Active and uncontrolled infections requiring intravenous antibiotic or antiviral treatment 10) Known/suspected hypersensitivity against ICT01, human or humanized IgGs, IL-2 (Proleukin®), pembrolizumab or their excipients 11) Seropositive (except after vaccination or confirmed cure for hepatitis) for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) 12) 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 13) Dementia or altered mental status that would prohibit informed consent 14) Other severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study assessed by the Investigator 15) Active drug or alcohol abuse as assessed by the Investigator 16) Patients with uncontrolled and symptomatic brain metastases or seizure disorders. Patient with asymptomatic brain metastases are allowed provided they are stable and off therapeutic steroids for at least 4 weeks 17) Patients who have received vaccination with a live-attenuated vaccine within 30 days prior to study treatment initiation 18) Patients with contraindications to IL-2 according to the SmPC, including organ allografts and pre-existing severe major organ dysfunction. 19) For cohorts 13, 14 and 15 in combination with Pembrolizumab: patients with prior allogeneic HSCT or solid organ transplant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part I Characterize the overall safety and tolerability profile of a range of intravenous (IV) doses of ICT01 in combination with low-dose subcutaneous (LDSC) IL-2 in patients with advanced solid tumors tumors and in combination with LDSC-IL-2 and pembrolizumab in patients with advanced melanoma or pancreatic ductal adenocarcinoma (PDAC). Part II Characterize the preliminary antitumor activity according to RECIST of IV ICT01 in combination with LDSC IL-2 in patients with a specific solid tumor indication with or without pembrolizumab (up to 2 indications for Part 2 will be determined after Part 1). ;Secondary Objective: Part I 1.Characterize the pharmacodynamic activity of ICT01 in combination with LDSC IL-2 to increase the number and activation status of ?9d2-T cells in the blood and tumors of patients with advanced solid tumors and in combination with pembrolizumab in patients with advanced melanoma or PDAC. 2.Characterize the preliminary anti-tumor activity according to Response Evaluation Criteria In Solid Tumors (RECIST)of a range of IV doses of ICT01 in combination with LDSC IL-2 in patients with advanced solid tumors and in combination with pembrolizumab in patients with advanced melanoma or PDAC. Part II 1.Characterize the overall safety and tolerability of IV ICT01 in combination with LDSC IL-2 with or without pembrolizumab. 2.Characterize the PD activity of ICT01 in combination with LDSC IL-2 with or without pembrolizumab to increase the number and activation status of ?9d2-T cells in the blood and tumors of patients with a specific solid tumor indication.;Primary end point(s): Part I The primary objective of safety and tolerability will be evaluated in this study by the incidence, severity, and relationship of the following endpoints during the study: DLTs, TEAEs, fatal TEAEs, TESAEs, TEAEs leading to discontinuation of study treatment or treatment modifications; and incidence and severity of clinically significant findings on clinical | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part I • PD endpoint will be the change from baseline in counts and activation status of ?9d2 T cells in PBMCs and tumor biopsies, with a significant expansion of circulating ?9d2 T cells, and an increase in ?9d2 T cells in the tumor biopsies at Day 28, considered key PD endpoints. • The preliminary antitumor activity endpoint will be DCR as per RECIST. If appropriate, Objective response rate (ORR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) will also be analyzed as endpoints. iRECIST will be considered exploratory and used for treatment decisions. Part II ? The secondary endpoints relating to the primary objective are ORR, TTP, PFS and OS according to RECIST. ? The key secondary safety endpoints will be evaluated by incidence, severity, and relationship of DLTs, TEAEs, fatal TEAEs, TESAEs, TEAEs leading to discontinuation of study treatment, and TEAEs leading to discontinuation of study; and clinically significant findings on clinical laboratory tests, vital signs, ECGs, and physical examinations. ? PD: Change from baseline in counts and activation status of ?9d2 T cells in PBMCs and tumor biopsies, with a significant expansion of circulating ?9d2 T cells, and an increase in ?9d2 T cells in the tumor biopsies at Day 28, considered key PD endpoints. ;Timepoint(s) of evaluation of this end point: On-going throughout the duration of the study | — |
Countries
Germany, Spain, United Kingdom
Contacts
Public ContactChief Medical Officer
ImCheck Therapeutics, Inc.
Outcome results
None listed