lungcancer Non-small cel lung carcinoma
Conditions
Interventions
None listed
Sponsors
Vrije Universiteit Medisch Centrum
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: For inclusion in the study subjects must fulfill all of the following criteria: * Have a histologically or cytologically confirmed diagnosis of stage IV, EGFR wt and EML4-ALK fusion negative NSCLC and have received at least one line of platinum based doublet chemotherapy. * Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations * Age > 18 years at time of study entry * Have a World Health Organisation (WHO) performance status of 0 or 1 * Life expectancy of more than 3 months. * Have measurable disease based on RECIST 1.1. * Must provide tissue from a histological biopsy of a tumor lesion that is not radiated prior to biopsy and obtained after the last line of systemic therapy to determine the PD-L1 status. * Willing to undergo up to two additional biopsies when the first 89Zr-MEDI4736 PET scan shows heterogeneous uptake. * Adequate normal organ and marrow function. * Females of childbearing potential must use reliable methods of contraception from the time of screening until 3 months after discontinuing study treatment. * Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
Exclusion criteria
Exclusion criteria: Subjects should not enter the study if any of the following exclusion criteria are fulfilled: * Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). Previous enrollment in the present study. * Participation in another clinical study with an investigational product during the last 4 weeks. * Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736. * History of another primary malignancy except for: * Malignancy treated with curative intent and with no known active disease *3 years before the first dose of study drug. * Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. * Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ. * Receipt of the last dose of anti-cancer therapy * 14 days prior to the first dose of study drug. * Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, 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 * Any unresolved toxicity (CTCAE grade <2) from previous anti-cancer therapy. * Any prior Grade *3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE >Grade 1 * Active or prior documented autoimmune disease within the past 2 years requiring systemic steroid treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids. NOTE: Subjects with vitiligo, Grave*s disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. * Active or prior documented inflammatory bowel disease (e.g., Crohn*s disease, ulcerative colitis) * History of primary immunodeficiency * History of allogeneic organ transplant * History of hypersensitivity to MEDI4736 or any excipient * 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 evidence of acute or chronic hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent * Known history of previous clinical diagnosis of tuberculosis * History of leptomeningeal carcinomatosis * Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving MEDI4736 * Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control * Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results * Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation and/or corticosteroids exceeding a daily dose equivalent of 10 mg prednisolone. Patients with asymptomatic brain metastases a
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| * To assess the safety of 89Zr-MEDI4736. * To assess uptake of 89Zr-MEDI4736 in tumor lesions. | — |
Secondary
| Measure | Time frame |
|---|---|
| * Assess uptake of 89Zr-MEDI4736 in normal tissues to evaluate the biodistribution and dosimetry. * Characterize tumor uptake heterogeneity between patients and within and between tumor lesions of the same patient * Correlate 89Zr-MEDI4736 tumor uptake with tumor and TIL PD-1 and PD-L1 expression as well as other blood and tissue parameters. * Correlate 89Zr-MEDI4736 organ uptake with irAEs. The focus will be on the lung, liver, thyroid, pancreas, kidneys and pituitary. | — |
Countries
Netherlands
Outcome results
None listed