Trials / Withdrawn
WithdrawnNCT06361810
PSMA Therapy and Immunotherapy in Kidney Cancer
A Phase 1/2 Open-label Study of Pembrolizumab Combined With PNT-2002 Radioligand Therapy in Patients With Metastatic Renal Cell Carcinoma
- Status
- Withdrawn
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 0 (actual)
- Sponsor
- Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
- Sex
- All
- Age
- 18 Years
- Healthy volunteers
- Not accepted
Summary
This is a multi-center, single arm open label phase 1b/2 study of pembrolizumab in combination with 177Lu-PNT2002 (also known as 177Lu-PSMA I\&T) 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 3.4 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 MTD/RP2D 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-1/PDL1 therapy based on objective response rate (ORR) by RECIST 1.1 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.
Conditions
Interventions
| Type | Name | Description |
|---|---|---|
| DRUG | Pembrolizumab | Pembrolizumab will be administer at 400 mg IV every 6 weeks in combination with 177Lu-PNT2002 until the maximum tolerated dose of 177Lu-PNT2002 is reached during the dose escalation phase. Pembrolizumab will be administer at 400 mg IV every 6 weeks for a maximum of 17 cycles (6 weeks in each cycle) during the dose expansion phase. |
| DRUG | 177Lu-PNT2002 | 177Lu-PNT2002 given intravenously every 8 weeks will be administered at 3.4 GBq, 6.1 Gbq, or 6.8 Gbq in combination with the standard dose of pembrolizumab 400 mg given intravenously every 6 weeks until the maximum tolerated dose is reached during the dose escalation phase. 177Lu-PNT2002 given intravenously every 8 weeks will be administered at the determined maximum tolerated dose for a maximum of 4 cycles in combination with the standard dose of pembrolizumab 400 mg given intravenously every 6 weeks for a maximum of 17 cycles. |
| DRUG | (F-18)-DCFPyL | Patients will be administered 18F-DCFPyL as a single bolus intravenous radioactive dose injection of 333 MBq (9 mCi) at screening, week 12 and week 24. |
Timeline
- Start date
- 2025-10-01
- Primary completion
- 2031-01-01
- Completion
- 2032-01-01
- First posted
- 2024-04-12
- Last updated
- 2025-08-19
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT06361810. Inclusion in this directory is not an endorsement.