64Cu-DOTA-pembrolizumab PET for the Study of PD1 Expression

PRIMARY OBJECTIVE:

I. To assess safety and tolerability of unlabeled pembrolizumab followed by 64Cu-tetraxetan (DOTA)-pembrolizumab positron emission tomography, at each dose level, by evaluation of toxicities including: type, frequency, severity, attribution, time course and duration.

SECONDARY OBJECTIVES:

I. Generate initial estimates of the biodistribution of the 64Cu-DOTA-pembrolizumab and the preferred dose of cold antibody.

II. Determine the dose of pre-administered unlabeled pembrolizumab that improves image quality by qualitative assessment by the radiologist of 64Cu-DOTA-pembrolizumab.

III. Evaluate the performance of 64Cu-DOTA-pembrolizumab in detecting tumor lesions.

OUTLINE: This is a dose-escalation study of 64Cu-DOTA-pembrolizumab.

Patients receive pembrolizumab intravenously (IV) over 30 minutes, and within 6 hours also receive 64Cu-DOTA-pembrolizumab via slow IV push over > 1 minute on day 0. Patients then undergo PET over 60 minutes on day 1.

After completion of study treatment, patients are followed up for 3 days.

Inclusion criteria

• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Ability to undergo standard PET imaging
• Plan to be treated with immunotherapy
• Karnofsky performance status (KPS) >= 50%
• Absolute neutrophil count (ANC) >= 1000/mm^3
• Platelet count >= 50/mm^3; platelet transfusions to help patients meet eligibility criteria are not allowed within 7 days before study enrollment
• Total bilirubin =< 1.5 x the upper limit of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN
• Calculated creatinine clearance >= 30 mL/min
• Woman of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods; condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization; true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (6 months after the last dose of 64Cu-anti-PD1 [pembrolizumab]-N-hydroxysuccinimide [NHS]-DOTA for women)
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control, e.g., either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men must also not donate sperm during the study and for 6 months after receiving the last dose of study drug

Exclusion criteria

• Prior exposure to pembrolizumab or other anti-PD1 therapy
• Unable to tolerate PET scan
• Any condition that would, in the investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Female patients who are lactating or have a positive pregnancy test during the screening period
• Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment
• Subject is receiving concurrent chemotherapy or biologic or hormonal therapy for cancer treatment. Subject is receiving bone marrow stimulatory factors (e.g., granulocyte-macrophage colony-stimulating factor [GM-CSF]). Note: Concurrent use of hormones for noncancer-related conditions (e.g., insulin for diabetes) is acceptable
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• Vaccination with live attenuated vaccines within 4 weeks of study agent administration
• Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration
• Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
• Chronic systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, computed tomography [CT] scan premedication)
• Subject has plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes), or primary amyloidosis
• Subject has known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) < 50% predicted normal. Note that FEV1 testing is required for patients suspected of having COPD and subjects must be excluded if FEV1 < 50%
• Subject has known allergies, hypersensitivity, or intolerance to monoclonal antibodies or human proteins, or their excipients
• Subject has history of primary immunodeficiency
• Subject is positive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B, or active hepatitis A or C
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)