A PET Imaging Agent (64Cu-DOTA-Pembrolizumab) for Determining Treatment Response Among Patients With Stage IV Non-small Cell Lung Cancer Receiving Pembrolizumab

Pilot Study of 64Cu-DOTA Pembrolizumab (64CDP) in Patients Receiving Stereotactic Body Radiation Therapy (SBRT) for Oligo-Progressive Non-Small Cell Lung Cancer (NSCLC)

This phase I trial studies the safety and side effects of a new positron emission tomography (PET) imaging agent called 64Cu-DOTA-pembrolizumab to see how well it works in determining treatment response for patients with stage IV non-small cell lung cancer (NSCLC) already receiving pembrolizumab. 64Cu-DOTA-pembrolizumab consists of a monoclonal antibody, pembrolizumab, that binds to a protein called PD-1 that is expressed on tumor cells. PET scans can then visualize the tumor cells using 64Cu, a radioactive substance. 64Cu-DOTA-pembrolizumab PET scans may be safe and useful to doctors in telling the difference between tumors that are still growing and areas that are not growing in patients with stage IV NSCLC receiving pembrolizumab treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8; Metastatic Malignant Neoplasm in the Brain; Oligoprogressive Lung Non-Small Cell Carcinoma
• Intervention / Treatment: Procedure: Computed Tomography; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Stereotactic Body Radiation Therapy; Radiation: Low Dose Radiation Therapy; Radiation: Copper Cu 64-DOTA-pembrolizumab

Detailed Description

PRIMARY OBJECTIVES:

I. To describe the safety of administering copper Cu 64-DOTA-pembrolizumab (64Cu-DOTA-pembrolizumab) for PET imaging in patients receiving SBRT for NSCLC during pembrolizumab therapy.

II. Evaluate 64Cu-DOTA-pembrolizumab maximum standard uptake value (SUVmax) at baseline for oligoprogressive lesion(s) versus (vs) lesions that were not progressing on pembrolizumab therapy.

SECONDARY OBJECTIVES:

I. Evaluate change in SUVmax in non-progressing lesions given low dose radiation therapy (LDRT).

II. Evaluate change in SUVmax on oligoprogressive lesions treated with SBRT. III. Compare change in SUV-max of 64Cu-DOTA-pembrolizumab (64CDP) from baseline to the follow-up scan on non-progressive lesions not given LDRT or SBRT.

IV. Evaluate the impact of different quantitative measures of PET avidity (e.g. SUVpeak, SUVmean, lean-body weight-adjusted, relative to average uptake in liver).

EXPLORATORY OBJECTIVE:

I. To summarize differences in SUVmax pre- and post-SBRT based on tumor location and clinical course for further hypothesis generation.

OUTLINE:

Patients receive standard of care (SOC) pembrolizumab intravenously (IV) on day 0, followed by 64Cu-DOTA-pembrolizumab IV over 5 minutes on day 1 and PET scan on day 2. Patients then receive SOC SBRT over 3-5 treatment fractions over a 10-12 day period (approximately days 8-18). Patients may also undergo low-dose radiation therapy (LDRT) over 3-5 treatment fractions over this 10-12 day period based on results of first 64CDP PET scan. Patients then receive SOC pembrolizumab IV on day 21 and 42, followed by 64Cu-DOTA-pembrolizumab IV over 5 minutes on day 43 and PET scan on day 44. Patients also undergo a computed tomography (CT) scan on study.

After completion of study treatment, patients are followed for 1 year.

• Study Type: Interventional
• Enrollment (Estimated): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Sagus Sampath
      • Contact: Sagus Sampath; Phone Number: 626-218-8240; Email: ssampath@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

  • Assent, when appropriate, will be obtained per institutional guidelines
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed stage IV non-small cell lung cancer
• Patients on single-agent pembrolizumab, who have been referred for SBRT for or oligo-progressive disease. A maximum of 6 sites will be allowed to receive SBRT on protocol
• Patients must have sites that are amenable to SBRT that are located in lymph nodes, bone/spine, or lung
• Brain metastases or cases with intra-cranial progression are allowed, but an additional extra-cranial site planned for SBRT is required
• Absolute neutrophil count (ANC) ≥ 1,000/mm^3

• Platelets ≥ 50,000/mm^3

  • NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
• Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 3.0 x ULN
• Alanine aminotransferase (ALT) ≤ 3.0 x ULN
• Creatinine clearance of ≥ 30 mL/min per 24 hour urine test or the Cockcroft-Gault formula

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test

  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Agreement by females and males of childbearing potential* to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy

  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Patient planned to stop pembrolizumab at time of referral for SBRT
• Vaccination with live attenuated vaccines within 4 weeks of study agent administration except forthcoming coronavirus disease 2019 (COVID-19) and flu vaccines

• Subject is currently using or has used immunosuppressive medication within 14 days prior to the study agent administration with the exception of:

  • Intranasal, topical, inhaled, or local steroid injections (e.g., intra-articular injection)
  • Chronic systemic corticosteroids at physiologic doses not to exceed 5 mg/day of prednisone or equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., infusion-related reactions, CT scan premedication)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• Clinically significant uncontrolled illness
• Infection requiring systemic antibiotic therapy within 14 days prior to start of study treatment
• Patient unable to tolerate PET scan even with anxiolytic medications
• Other active metastatic malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (pembrolizumab, 64CDP, SBRT, LDRT); Patients receive SOC pembrolizumab IV on day 0, followed by 64Cu-DOTA-pembrolizumab IV over 5 minutes on day 1 and PET scan on day 2. Patients then receive SOC SBRT over 3-5 treatment fractions over a 10-12 day period (approximately days 8-18). Patients may also undergo LDRT over 3-5 treatment fractions over this 10-12 day period based on results of first 64CDP PET scan. Patients then receive SOC pembrolizumab IV on day 21 and 42, followed by 64Cu-DOTA-pembrolizumab IV over 5 minutes on day 43 and PET scan on day 44. Patients also undergo a CT scan on study.

Procedure: Computed Tomography; Undergo CT; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475; MK3475; SCH-900475; BCD-201; Pembrolizumab Biosimilar BCD-201; Pembrolizumab Biosimilar QL2107; QL2107; GME 751; GME751; Pembrolizumab Biosimilar GME751; MK 3475; SCH900475; Pembrolizumab Biosimilar RPH-075; RPH 075; RPH-075; RPH075; Pembrolizumab Biosimilar SB27; SB 27; SB-27; SB27; Procedure: Positron Emission Tomography; Undergo PET; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Radiation: Stereotactic Body Radiation Therapy; Undergo SBRT; Other Names: SBRT; SABR; Stereotactic Ablative Body Radiation Therapy; Radiation: Low Dose Radiation Therapy; Undergo LDRT; Other Names: Low Dose Radiation; Radiation: Copper Cu 64-DOTA-pembrolizumab; Given IV; Other Names: 64Cu-DOTA-pembrolizumab; 64Cu-labeled Pembrolizumab; 64Cu-pembrolizumab; Copper Cu 64 Pembrolizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment-related adverse event rates	Will be assessed by Common Terminology Criteria for Adverse Events version 5.0, delineated by grade and attribution. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.	Up to 14 days after 64Cu-DOTA-pembrolizumab infusion
64Cu-DOTA-pembrolizumab maximum standard uptake value (SUVmax)	Will evaluate CDP SUVmax at baseline for oligoprogressive lesions(s) versus lesions that are not progressing on pembrolizumab therapy. For this comparison, each patent will have both type of lesion(s) to be eligible. If the patient has more than one oligoprogressive lesion, the median SUVmax over the oligoprogressive lesions will be the key metric. Similarly if the patient has more than one non-oligoprogressive lesion the median SUVmax will be the key metric for that type of lesion within a patient. Only lesions measuring at least 2cm will be considered and if > 5 lesions, of either class, the target lesions will be identified before the CDP scan and if two qualifying lesions of the two different groups are in the same organ, they will be selected preferentially as the target lesions. As a result for each patient will have an SUVmax for oligoprogressive disease and an SUVmax for non-oligoprogressive disease.	Day 2 and day 44

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in SUV-max of 64CDP in non-progressing lesions that were given low dose radiation therapy	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-stereotactic body radiation therapy (SBRT). Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44
Change in SUV-max of 64CDP in oligoprogressive lesions that were given SBRT	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT. Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44
Change in SUV-max of 64CDP in non-progression lesions not given LDRT or SBRT	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT. Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44
Change in SUVpeak	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT. Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44
Change in SUVmean	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT. Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44
Change in lean-body weight-adjusted	T-tests (paired) will be used to test changes in 64-CDP uptake in radiated metastatic lesions pre- and post-SBRT. Non-parametric tests may also be explored in addition to the t-test.	Day 2 and day 44

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sagus Sampath, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): September 14, 2026
• Primary Completion (Estimated): December 22, 2028
• Study Completion (Estimated): December 22, 2028

Study Registration Dates

• First Submitted: May 26, 2026
• First Submitted That Met QC Criteria: May 26, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Physical Phenomena; Chemistry Techniques, Analytical; Spectrum Analysis; Stereotaxic Techniques; Neurosurgical Procedures; Radiotherapy; Radiation; pembrolizumab; Magnetic Resonance Spectroscopy; Radiosurgery
• Other Study ID Numbers: 25261 (Other Identifier: City of Hope Medical Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-03734 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No