Ignite Creation Date:
2024-05-06 @ 8:23 PM
Last Modification Date:
2024-10-26 @ 3:26 PM
Study NCT ID:
NCT06361810
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-04-12
First Post:
2024-04-08
Brief Title:
PSMA Therapy and Immunotherapy in Kidney Cancer
Sponsor:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Organization:
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Overview
Official Title:
A Phase 12 Open-label Study of Pembrolizumab Combined With PNT-2002 Radioligand Therapy in Patients With Metastatic Renal Cell Carcinoma
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a multi-center single arm open label phase 1b2 study of pembrolizumab in combination with 177Lu-PNT2002 also known as 177Lu-PSMA IT radiopharmaceutical therapy in patients with metastatic clear cell renal cell carcinoma RCC who have progressed after prior treatment with anti-programmed cell death protein 1 PD1 or PD-L1 immune-checkpoint inhibitors ICIs The study comprises 2 phases an open-label Phase 1b dose escalation portion followed by a Phase 2 dose expansion portion Investigators hypothesize that pembrolizumab in combination with 177Lu-PNT2002 in in patients with metastatic clear cell RCC at a biologically active dose will result in tolerable safety profile and it will lead to improved radiological objective responses in patients who have progressed after prior treatment with standard anti-PD1 or anti- Programmed Cell Death Ligand 1 PDL1 immune-checkpoint inhibitor containing regimen when compared to historic controls Patients in both phases will have prostate-specific membrane antigen PSMA positron emission tomography PET imaging with the radiotracer F-18-DCFPyl to help detect any spread of the cancer
Detailed Description:
In the dose escalation phase three dose levels of 177Lu-PNT2002 given intravenously every 8 weeks starting from 34 gigabequerel GBq in combination with the standard dose of pembrolizumab 400 mg given intravenously every 6 weeks After determining the maximum tolerated dose MTD or the recommended Phase 2 Dose RP2D the study will proceed to the dose expansion phase and in this portion of the study patients will receive 177Lu-PNT-2002 intravenously every 8 weeks at the MTDRP2D for a maximum of 4 cycles in combination pembrolizumab 400 mg intravenously every 6 weeks for a maximum of 17 cycles
The primary objective of the phase 1b portion of the study is to determine the MTD or RP2D of 177Lu-PNT2002 radiopharmaceutical therapy in combination with pembrolizumab in patients with metastatic clear cell RCC The primary objective of the phase 2 portion of the study is to evaluate the efficacy of 177Lu-PNT2002 in combination with pembrolizumab in patients with metastatic clear cell RCC who progressed on prior anti PD-1PDL1 therapy based on objective response rate ORR by RECIST 11 criteria
Patients in both phases will receive PSMA-PET with F-18-DCFPyl at screening 12 weeks and 24 weeks F-18-DCFPyl was developed as a diagnostic radiotracer for the detection of prostate cancer and was FDA approved in 2021 for the detection of PSMA positive lesions in men with prostate cancer However PSMA is not entirely prostate-specific as it has been shown to be present on neovascular endothelium of numerous solid tumors including RCC Prior studies have demonstrated high sensitivity and specificity of the detection of metastatic clear cell RCC lesions using PET imaging with various PSMA radiotracers such as F-18-DCFPyl Based on this the high expression of PSMA in RCC and the synergy of PSMA radiopharmaceuticals with ICIs such as pembrolizumab provide a novel treatment strategy in RCC
The primary objective of the phase 1b portion of the study is to determine the MTD or RP2D of 177Lu-PNT2002 radiopharmaceutical therapy in combination with pembrolizumab in patients with metastatic clear cell RCC The primary objective of the phase 2 portion of the study is to evaluate the efficacy of 177Lu-PNT2002 in combination with pembrolizumab in patients with metastatic clear cell RCC who progressed on prior anti PD-1PDL1 therapy based on objective response rate ORR by RECIST 11 criteria
Patients in both phases will receive PSMA-PET with F-18-DCFPyl at screening 12 weeks and 24 weeks F-18-DCFPyl was developed as a diagnostic radiotracer for the detection of prostate cancer and was FDA approved in 2021 for the detection of PSMA positive lesions in men with prostate cancer However PSMA is not entirely prostate-specific as it has been shown to be present on neovascular endothelium of numerous solid tumors including RCC Prior studies have demonstrated high sensitivity and specificity of the detection of metastatic clear cell RCC lesions using PET imaging with various PSMA radiotracers such as F-18-DCFPyl Based on this the high expression of PSMA in RCC and the synergy of PSMA radiopharmaceuticals with ICIs such as pembrolizumab provide a novel treatment strategy in RCC
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None