A pilot study, defining the Immunophenotype of immunotherapy resistance with 89Zr- Durvalumab (MEDI4736) and CD8 T-cell PET/CT.

Phase 1

Recruiting

• Conditions: on-small cell lung cancer; Non-small cell lung cancer; Cancer - Lung - Non small cell

• Registration Number: ACTRN12624000348550
• Lead Sponsor: Peter MacCallum Cancer Centre

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-27
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Written and informed consent provided

18 years or above

Body weight above 30kg

Life expectancy equivalent to 12 weeks

Primary tumour characteristics: Any stage non-small cell lung cancer (AJCC v.8)

Patients are planned to receive radiotherapy to sites of progressive disease

Adequate organ and marrow function as defined below:

Absolute neutrophil count greater than 1.5 x 109/L (1500 per mm3)

Platelets greater than 100 x 109/L (100,000 per mm3)

Haemoglobin greater or equal to 9.0 g/dL (5.59 mmol/L)

Serum creatinine CL greater than 50 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976)

(eGFR) greater than 50ml/min as measured using the MDRD formula (Modification of Diet in Renal Disease).

Serum bilirubin less than or equal to 1.5 x institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert’s syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of haemolysis or hepatic pathology), who will be allowed only in consultation with their physician

AST (SGOT)/ALT (SGPT) less than or equal to 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be less than or equal to 5x ULN

Women will be considered post-menopausal according to the following age-specific requirements:

Women under the age of 50 would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and, if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution

Women aged 50 and above would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses over a year ago, had chemotherapy-induced menopause with last menses over a year ago, or underwent surgical sterilization (bilateral oophorectomy or hysterectomy

Evidence of post-menopausal status or negative serum pregnancy test at baseline for female participants over the age of 50 or evidence that they have undergone surgical sterilization (bilateral oophorectomy or hysterectomy with oophorectomy). Subsequent pregnancy tests performed prior to PET imaging may be urinary or serum.

Eastern Cooperative Group Oncology Group (ECOG) performance score of 0-2.

Patient 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

Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, 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. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.

For patients who have received prior immunotherapy, including anti PD-1, PD-L1 and CTLA-4 therapy:

Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of greater than 10 mg prednisone or equivalent per day.

All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.

Must not have experienced a greater than or equal to Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of greater than or equal to Grade 2 are permitted to enrol if they are stably maintained on appropriate replacement therapy and are asymptomatic.

Vascular access or EBUS or mediastinal biopsy) that would prevent administration of study drug.

Active or prior documented autoimmune disease within the past 2 years. NOTE: Patients 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 organ transplant that requires therapeutic immunosuppression.

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 patient known to have 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 patient to give written informed consent.

Known active hepatitis infection, positive hepatitis C virus (HCV) antibody, hepatitis B virus (HBV) surface antigen (HBsAg) or HBV core antibody (anti-HBc), at screening. Participants with a past or resolved HBV infection (defined as the presence of antiHBc and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

Participants co-infected with HBV and HCV, or co-infected with HBV and HDV, namely: HBV positive (presence of HBsAg and/or anti HBcAb with detectable HBV DNA); AND

HCV positive (presence of anti-HCV antibodies); OR

HDV positive (presence of anti-HDV antibodies).

Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV?1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).

Receipt of live atten

Study & Design

• Study Type: Interventional
• Study Design: Not specified