64Cu-GRIP B in Patients With Advanced Malignancies

For Cohort A, the frequency and severity of adverse events following 64Cu-GRIP B injection will be descriptively reported, using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

For Cohort A, the tracer kinetics is measured in the organs and total-body, and the % of injected activity for each time point will be recorded for participants in Cohort A. This information is used as input for organ and whole-body effective dose calculation using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM). This will provide the data of whole-body effective dose (millisievert (mSv)/megabecquerels (MBq)), and organ doses.

Pharmacokinetic (PK) parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug that needs to be absorbed.

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the maximum concentration (Cmax) after administration of a drug that needs to be absorbed.

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the area under the concentration-time curve (AUC) from hour 0 to the last measurable concentration (AUC0-t; min*unit/mL)

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the AUC extrapolated to infinity (AUC0-∞; min*unit/mL)

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the volume of plasma which is completely cleared of a substance per minute (mL/min).

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the apparent terminal elimination rate constant.

PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute apparent terminal elimination half-life (t1/2; min).

For Cohorts B, C and D, descriptive statistics will be used to summarize the change in SUVmax from baseline to 8 weeks at lesion level for participants in Cohorts B & C.

For Cohorts B, C and D, descriptive statistics will be used to summarize the change in the ratio of SUVmax/SUVave from baseline to 8 weeks at lesion level for participants in Cohorts B & C.

For Cohorts B, C and D, the frequency and severity of adverse events following 64Cu-GRIP B injection will be descriptively reported

For Cohorts B, C and D, the mead/standard deviation (sd) (median and range, if normality assumption does not hold) for intra-tumoral SUVmax within metastatic lesions will be descriptively reported, to assess for intra-tumoral heterogeneity and differences in uptake by site of disease.

For Cohorts B, C and D, the percentage of metastatic lesions detected on conventional imaging that are also detected on baseline 64Cu-GRIP B PET will be descriptively reported with 95% confidence intervals.

For the subset of patients in Cohort B experiencing Grade ≥ 2 immune-related adverse event who have 64Cu-GRIP B PET performed within 14 days of onset of event, the mean change from baseline in involved organ site(s) uptake on PET will be descriptively reported along with sd (or median with range) at lesion-level

For the subset of patients in Cohort B experiencing Grade >= 2 immune-related adverse event who have 64Cu-GRIP B PET performed within 14 days of onset of event, the mean change from baseline in involved organ site(s) uptake on PET will be descriptively reported along with sd (or median with range) at patient-level

For Cohort B, C and D , to analyze the association between the baseline in SUVmax and with subsequent response by RECIST 1.1 for Cohort B and modified RECIST 1.1/PCWG3 criteria, metastatic lesions will be segregated based on objective response by RECIST 1.1 criteria on follow up conventional imaging.

For Cohorts B, C and D, to assess the association between the baseline SUVmax with progression-free survival, defined as the time from date of initiation of checkpoint inhibition to subsequent progression by Prostate Cancer Clinical Trials Working Group 3 (PCWG3)/RECIST criteria, the participant cohort will be dichotomized above and below the median PFS.

For cohort C, to assess the association between the baseline in SUVmax with the patient cohort will be dichotomized into PSA50 vs. non-PSA50 responders.

For Cohorts B, C and D,to assess the association between the baseline in SUVmax with the patient cohort will be dichotomized into irAE vs. non-irAE reporters.