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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
Undergo CT
Given IV
Undergo LDRT
Given IV
Undergo PET
Undergo SBRT
City of Hope Medical Center
Duarte, California, United States
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.
Time frame: 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.
Time frame: Day 2 and day 44
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 2 and day 44
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