Inoperable advanced or metastatic non-small cell lung cancer (NSCLC) 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: PT Classification code 10029515 Term: Non-small cell lung cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.1 Level: PT Cla
Conditions
Interventions
Product Name: UV1
Pharmaceutical Form: Powder and solution for solution for injection
INN or Proposed INN: Not available
CAS Number: 1331848-79-3
Other descriptive name: P719-20
Concentration unit: mg
Sponsors
Vestre Viken Health Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following criteria to be eligible for study entry: 1.Histologically confirmed NSCLC stage IIIB/IIIC or IV not amenable for curative tretment, with PD-L1 = 50% measured by a validated method, and eligible for anti-PD-1/PD-L1 treatment monotherapy in the first-line setting 2.At least one lesion, not previously irradiated and not chosen for biopsy during the study screening period, that can be accurately measured at baseline according to RECIST 1.1 3.Subjects who received previous neo-adjuvant or adjuvant systemic therapy (other than immunotherapies) will be eligible if neo-adjuvant or adjuvant therapy was completed at least 12 months prior to the development of metastatic disease. Last dose of neoadjuvant or adjuvant therapy must be more than 12 months prior to enrollment/randomization 4.Available unstained archived tumour tissue sample in sufficient quantity to allow for analyses. At least fifteen unstained slides or a tumour block (preferred) 5.Male and female age = 18 years at time of signing the ICF 6.Male and female age = 18 years at time of signing the ICF 7.Adequate organ function as defined below -Haemoglobin =9.0 g/dL -Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3) -Platelet count =100 x 109/L (>75,000 per mm3) -Serum bilirubin =1.5 x institutional upper limit of normal (ULN). -AST (SGOT)/ALT (SGPT) =2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be =5x ULN -Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL >40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 – Age) x 0.85 72 x serum creatinine (mg/dL) 8.Written informed consent obtained prior to any study specific procedure 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 69 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 69
Exclusion criteria
Exclusion criteria: The subject must be excluded from participating in the study if the subject has/is: 1.Previous treatment with a PD-1 or PD-L1 inhibitor, including pembrolizumab or any other agent targeting immune checkpoints 2.Previous malignancy (except non-melanoma skin cancer and the following in situ cancers: bladder, gastric, oesophageal, colon, endometrial, cervical, melanoma or breast) unless a complete remission was achieved at least 2 years prior to study entry 3.Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids (prednisone >10 mg or equivalent). Surgery, radiation and/or corticosteroids (any dose >10 mg prednisone equivalent) must have been completed = 2 weeks prior to registration 4.Known history of leptomeningeal carcinomatosis 5.Uncontrolled seizures. 6.Current or prior use of immunosuppressive medication within 28 days before the first dose of pembrolizumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Steroid premedication given as prophylaxis for imaging contrast allergy should not be counted for this criterion 7.Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome) within the past 2 years. Subjects with vitiligo, alopecia, Grave's disease, or psoriasis not requiring systemic treatment (within the past 3 years) are not excluded 8.History of primary immunodeficiency 9.History of allogeneic organ transplant 10.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any subject known to have psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent 11.Active infection including tuberculosis (clinical evaluation including: physical examination findings, radiographic findings, positive PPD test, etc.), hepatitis B (known positive HBV surface antigen [HBsAg] result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies as defined by a positive ELISA test). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA. HIV testing is not required in the absence of clinical suspicion 12.Pregnant or lactating women 13.Live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving pembrolizumab 14.Any condition that, in the opinion of the investigator, would interfere with the evaluation of study treatment or interpretation of patient safety or study results 15.History of allergy or hypersensitivity to any of the active substances or excipients in the study drug 16.Involvement in the planning and/or conduct of the study (investigator staff and/or staff at the study site) 17.Judgment by the investigator that the subject should not participate in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the phase 2 study is to induce a meaningful Progression-Free Survival (PFS) benefit in patients with stage IIIB/IIIC or stage IV NSCLC by treating with anti-PD-1/PD-L1 treatment and UV1 vaccination versus anti-PD-1/PD-L1 treatment alone. ;Secondary Objective: To compare overall survival (OS), objective response rate (ORR), disease control rate (DCR), time to response (TTR) and duration of response (DOR) according to Response Evaluation Criteria in Solid Tumours, version 1.1 (RECIST 1.1), in patients who receive pembrolizumab with patients who receive anti-PD-1/PD-L1 treatment in combination with UV1 vaccination. To determine the safety and tolerability in patients who receive anti-PD-1/PD-L1 treatment compared to patients who receive anti-PD-1/PD-L1 treatment in combination with UV1 vaccination. Explorative: To investigate possible biological markers for response, resistance and toxicity Explorative: To investigate the role of PET/CT in early response evaluation ;Primary end point(s): Primary endpoints will be Progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours (RECIST v1.1).;Timepoint(s) of evaluation of this end point: Throughout the trial. Radiologic assessments will be performed every eight week during the patients first six months included in the trial, and every 12. week thereafter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Survival (OS),m Objective Response Rate (ORR), Disease Control Rate (DCR), Time To Response (TTR) and Duration of Objective Response (DOR).;Timepoint(s) of evaluation of this end point: Throughout the trial | — |
Countries
Norway
Contacts
Public ContactOdd Terje Brustugun
Vestre Viken Health Trust
Outcome results
None listed