HLA-A*0201 positive patients with advanced antigen-positive cancer with a histologic diagnosis of Non small cell lung carcinoma (NSCLC), melanoma, urothelial carcinoma, or synovial sarcoma with antigen positivity for NY-ESO-1 and/or LAGE-1A MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: LLT Classification code 10025665 Ter
Conditions
Interventions
Product Name: IMCnyeso
Product Code: IMCnyeso
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: IMCNYESO
Current Sponsor code: IMCNYESO
Concentration unit: mg/ml milligra
Sponsors
Immunocore Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all the following inclusion criteria to be eligible for inclusion in the study: General 1.Male or female patients age = 18 years of age at the time of informed consent 2.Ability to understand and provide written informed consent prior to undergoing any studyprocedures 3.Life expectancy of > 3 months as estimated by the Investigator 4.Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 at Screening 5.In the opinion of the Investigator, all other relevant medical conditions must bewell-managed and stable for at least 28 days prior to first administration of study drug HLA and Tumor Antigen Testing 6.HLA-A*02:01 positive as confirmed by the central laboratory 7.NY-ESO-1 and/or LAGE-1A positive tumor confirmed by the central laboratory Phase I: Disease Under Study and Prior Anti-Cancer Treatment 8.Histologically confirmed diagnosis of advanced NSCLC, melanoma, urothelial carcinoma,or synovial sarcoma 9.Patients must be relapsed from, refractory to, or intolerant to all approved and availableclasses of therapy known to provide clinical benefit for their condition Phase II: Disease Under Study and Prior Anti-Cancer Treatment 10.Histologically confirmed diagnosis of advanced NSCLC, urothelial carcinoma, or synovialsarcoma 11.Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1criteria (Section 13.1) 12.A minimum of 10 patients enrolled in Phase II must have disease that is amenable tobiopsy, and consent to provide biopsies during Screening and on treatment 13.Patients will have received the following previous therapies. These therapies must havebeen given for unresectable / metastatic disease or given in the adjuvant setting if diseaseprogression occurred during or within 6 months of completing adjuvant therapy •NSCLC — PD-1/PD-L1 inhibitor. Patients with a genomic tumor aberration (eg, EGFR,ALK) that is targeted by Health Authority-approved agent(s) must be relapsed from,refractory to, or intolerant of relevant targeted agent(s) •Urothelial cancer — PD-1/PD-L1 inhibitor •Synovial sarcoma — at least 1 prior systemic chemotherapy regimen Contraception 14.Female patients should either be of non-childbearing potential or must agree to use highly effective methods of contraception from Screening until 6 months following administration of the last dose of study drug (see Section 6.14) 15.Male patients must be surgically sterile or use double barrier contraception from enrollment through treatment and for 6 months Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 53 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Patients with any of the following will not be included in the study: Disease Under Study and Prior Anti-Cancer Treatment -Presence of symptomatic or untreated CNS metastases, leptomeningeal disease, cord compression, or CNS metastases that require doses of corticosteroids within 3 weeks prior to the planned first administration of study drug. -Systemic anticancer therapy for disease under study within 2 weeks of the planned first administration of study treatment. For cytotoxic or immunotherapy agents that can present with major delayed toxicity, a 4-week washout period is required -Radiotherapy within 2 weeks of the planned first administration of study drug. -Presence of National Cancer Institute Common Terminology Criteria for AEs = Grade 2 toxicity due to prior cancer therapy (except Grade 2 alopecia, stable Grade 2 peripheral neuropathy, Grade 2 endocrine disorder [on stable replacement doses and without symptoms]Grade 2 hypophosphatemia [on appropriate replacement therapy] and Grade 2 ototoxicity) Laboratory Parameters -Patient with any out-of-range laboratory values defined as shown below. Hematology evaluations must be performed = 7 days after any blood or blood product transfusion and= 14 days after any dose of hematologic growth factor. Creatinine clearance (calculated using Cockcroft-Gault formula or measured) 1.5 × upper limit of normal (ULN); NOTE: for patients with Gilbert's syndrome; exclude if total bilirubin > 3.0 × ULN or direct bilirubin > 1.5 × ULN) Alanine aminotransferase (ALT) > 3 × ULN Aspartate aminotransferase (AST) > 3 × ULN Absolute neutrophil count (ANC) 470 msec on Screening ECG or known history of congenital long QT syndrome -History of acute myocardial infarction or unstable angina pectoris 10mg daily[QD] or the equivalent) or any other immunosuppressive medication at any dose level that could interfere with the action of the study drugs, in the opinion of the PI -Treatment for well controll
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: To identify the MTD and/or the RP2D of IMCnyeso, as a monotherapy, when administered weekly to patients with advanced NSCLC, melanoma, urothelial cancer, and synovial sarcoma Phase II: To assess the preliminary anti-tumor activity of IMCnyeso as monotherapy in advanced NSCLC, urothelial cancer, and synovial sarcoma ;Secondary Objective: Phase II: To characterize the safety and tolerability of IMCnyeso Phase I and Phase II: To assess the preliminary anti-tumor activity of IMCnyeso as monotherapy To characterize the PK profile of IMCnyeso as monotherapy To evaluate the preliminary incidence of anti-IMCnyeso antibody formation following multiple infusions of IMCnyeso Exploratory:To characterize the relationship between expression levels of NY-ESO-1 and LAGE-1A in the tumor and anti-tumor activity of IMCnyeso as monotherapy To assess potential pharmacodynamic changes in systemic and intratumoral immune response observed following IMCnyeso treatment To assess potential predictors of efficacy of IMCnyeso ;Primary end point(s): Phase I Incidence of dose-limiting toxicities Incidence and severity of AE and SAE Changes in laboratory parameters, vital signs, and ECGs Dose interruptions, reductions, and discontinuations Phase II BOR as determined by RECIST v1.1 ;Timepoint(s) of evaluation of this end point: Within Each Treatment Cycle Defined As Every 28 Days and In Accordance With Section 13.4 and Table 13 -13 (Study Schedule and Assessment) of The Study Protocol | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase II - Incidence and severity of AE and SAE Changes in laboratory parameters, vital signs, and ECGs Dose interruptions, reductions, and discontinuations Phase I and II Phase I: BOR, PFS, and DoR by RECIST v1.1; OS Phase II: PFS, and DoR by RECIST v1.1; OS Serum PK parameters (eg, AUC, Cmax, Tmax, t1/2) after single and multiple doses Incidence of anti- IMCnyeso antibody formation and its impact on PK Exploratory Tumor expression and localization of NY-ESO-1 and LAGE-1A Changes in frequency and phenotype of tumor-infiltrating lymphocytes Changes in serum chemokine / cytokine concentrations; changes in peripheral blood lymphocyte counts, activation, and phenotype; changes in gene expression profile (mRNA) Changes in ctDNA Tumor expression and localization of biomarkers (which may include, but not be limited to PD-1, PD-L1, HLA-DR, CTLA-4, CD3, CD8 and TIL counts) Soluble blood markers (eg, chemokines / cytokines) Cell-based markers (eg, Tregs, MDSCs) Within Each Treatment Cycle Defined As Every 28 Days and In Accordance With Section 13.4 and Table 13-13 (Study Schedule and Assessment) of The Study Protocol ;Timepoint(s) of evaluation of this end point: Within Each Treatment Cycle Defined As Every 28 Days and In Accordance With Section 7 and Table 7-1 (Study Schedule and Assessment) of The Study Protocol | — |
Countries
Canada, United Kingdom, United States
Contacts
Public ContactEric Phillips
Immunocore Ltd.
Outcome results
None listed