This is a phase I dose-escalation study of 225Ac-J591 administered together with 177Lu-PSMA small molecule. Both drugs are designed to deliver radiation to prostate cancer cells; they are known as radionuclide conjugates (radiation linked to antibodies/molecules that recognize prostate cancer cells). This phase of the study (phase I) will determine the highest dose of the study intervention that can be safely given.
Histologically or cytologically confirmed adenocarcinoma of prostate
Documented progressive metastatic CRPC based on Prostate Cancer Working Group 3 (PCWG3) criteria, which includes at least one of the following criteria: PSA progression, Objective radiographic progression in soft tissue, New bone lesions
ECOG performance status of 0-2
Have serum testosterone < 50 ng/dL. Subjects must continue primary androgen deprivation with an LHRH/GnRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy
Implantation of investigational medical device ≤4 weeks of Treatment visit #1 (Day 1) or current enrollment in oncologic investigational drug or device study
Use of investigational drugs ≤4 weeks or <5 half-lives of Treatment visit # 1(Day 1) or current enrollment in investigational oncology drug or device study
Prior systemic beta-emitting bone-seeking radioisotopes. Prior radium-223 is allowed provided at least 90 days have lapsed since last dose
For the prior PSMA-TRT-naive cohort, prior PSMA-targeted radionuclide therapy is not allowed (prior PSMA-targeted isotopes used for imaging/diagnostic purposes are allowed, as is prior PSMA-targeted therapy that does not involve therapeutic radionuclides); For the 177Lu-PSMA small molecule exposed cohort, no dose limiting toxicity may have been observed during/after therapy with prior treatment and all other entry criteria must be met
Single group
225Ac-J591
Drug30 - 40 KBq/kg (dose-escalation) every 8 weeks, for up to 2 cycles. Administered together with 177Lu-PSMA-617. Intravenous administration.
177Lu-PSMA-617
Drug6.8 - 7.4 GBq received every 8 weeks, for up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.
68Ga-PSMA-11
Drug\[185 ±74 MBq or 5 ±2 mCi\] intravenous during screening, 12 weeks, 24 weeks. Imaging agent for PSMA PET/CT.
177Lu-PSMA-I&T
Drug6.8 GBq received every 8 weeks, up to 2 cycles. Administered together with 225Ac-J591. Intravenous administration.
Dose limiting toxicity (DLT) of 225Ac-J591 and 177Lu-PSMA small molecule
DLTs will be measured by utilizing the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Cumulative maximum tolerated dose (MTD) or recommended phase II dose 225Ac-J591 and 177Lu-PSMA small molecule
The dose that produces an "acceptable" level of toxicity or that, if exceeded, would put subjects at "unacceptable" risk for toxicity. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which no more than one patient out of six experienced dose-limiting toxicity (DLT).
Proportion of PSMA+ subjects (by imaging criteria) with >50% PSA decline following treatment with the combination of 225Ac-J591 and 177Lu-PSMA small molecule
Proportion of patients achieving 50% or greater PSA decline (relative to baseline/pre-treatment PSA). Response may occur at any time following treatment initiation and prior to going off study or initiation of new therapy.
Change in biochemical progression-free survival
PSA progression will be defined as a rise of \> 25% above either the pretreatment level or the nadir PSA level (whichever is lowest). PSA must increase by \> 2 ng/ml to be considered progression.
Change in circulating tumor cells (CTC) count
CTCs will be analyzed through blood specimen collection via CellSearch methodology lab testing
Number of participants with radiographic response
Response evaluation criteria in solid tumors RECIST (Version 1.1) criteria with prostate cancer working group 3 (PCWG3) modifications will be used.
Number of participants with adverse events
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 is used to grade all adverse events
Click on the lead sponsor to view all of their trials.
