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

NCT07619599 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 25261NCI-2026-03734P30CA033572
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Metastatic Lung Non-Small Cell Carcinoma; Metastatic Malignant Neoplasm in the Brain; Oligoprogressive Lung Non-Small Cell Carcinoma; Stage IV Lung Cancer AJCC v8

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Change in SUV-max of 64CDP in non-progressing lesions that were given low dose radiation therapy

  Day 2 and day 44

• Change in SUV-max of 64CDP in oligoprogressive lesions that were given SBRT

  Day 2 and day 44

• Change in SUV-max of 64CDP in non-progression lesions not given LDRT or SBRT

  Day 2 and day 44

• Change in SUVpeak

  Day 2 and day 44

• Change in SUVmean

  Day 2 and day 44

Study Arms (1)

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

EXPERIMENTAL

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; Radiation: Copper Cu 64-DOTA-pembrolizumab; Radiation: Low Dose Radiation Therapy; Biological: Pembrolizumab; Procedure: Positron Emission Tomography; Radiation: Stereotactic Body Radiation Therapy

Interventions

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Copper Cu 64-DOTA-pembrolizumab RADIATION

Given IV

Also known as: 64Cu-DOTA-pembrolizumab, 64Cu-labeled Pembrolizumab, 64Cu-pembrolizumab, Copper Cu 64 Pembrolizumab

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Low Dose Radiation Therapy RADIATION

Undergo LDRT

Also known as: Low Dose Radiation

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Positron Emission Tomography PROCEDURE

Undergo PET

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SABR, SBRT, Stereotactic Ablative Body Radiation Therapy

Treatment (pembrolizumab, 64CDP, SBRT, LDRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Lung Neoplasms

Interventions

Radiotherapy; Radiation; pembrolizumab; Magnetic Resonance Spectroscopy; Radiosurgery

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Physical Phenomena; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative

Study Officials

• Sagus Sampath

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2026
• First Posted: June 2, 2026
• Study Start (Estimated): September 14, 2026
• Primary Completion (Estimated): December 22, 2028
• Study Completion (Estimated): December 22, 2028
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

US (1)