PSMA Therapy and Immunotherapy in Kidney Cancer

NCT06361810 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: IRB00430008
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Metastatic Renal Cell Carcinoma; Metastatic Clear Cell Renal Cell Carcinoma

Keywords

Kidney Cancer; Pembrolizumab; 177Lu-PNT2002; Pylarify

Outcome Measures

Primary Outcomes (2)

• Safety assessed by the incidence of dose limiting toxicities.

  Number of incidences of dose limiting toxicities during days 1 to 28 of cycle 1.

  Day 28

• Objective response rate by RECIST 1.1 criteria

  Proportion of patients with an objective response, defined as Complete Response or Partial Response by RECIST 1.1. Dose expansion phase of the trial.

  3 years post therapy initiation

Secondary Outcomes (5)

• Progression free survival

  4 years post therapy initiation

• Safety as assessed by number of participants experiencing adverse events

  2 years post therapy initiation

• Disease control rates

  3 years post therapy initiation

• Duration of response to study therapy

  3 years post therapy initiation

• Overall survival rate

  4 years post therapy initiation

Study Arms (4)

177Lu-PNT2002 3.4 GBq

EXPERIMENTAL

177Lu-PNT2002 administered at 3.4 GBq intravenously (IV) every 8 weeks combined with the standard dose of pembrolizumab 400 mg IV every 6 weeks. 18F-DCFPyL administered as a single bolus intravenous radioactive dose injection of 333 megabecquerel (MBq) (9 mCi) at screening, week 12 and week 24.

Drug: Pembrolizumab; Drug: 177Lu-PNT2002; Drug: (F-18)-DCFPyL

177Lu-PNT2002 5.1 GBq

EXPERIMENTAL

177Lu-PNT2002 administered at 5.1 GBq intravenously (IV) every 8 weeks combined with the standard dose of pembrolizumab 400 mg IV every 6 weeks. 18F-DCFPyL administered as a single bolus intravenous radioactive dose injection of 333 MBq (9 mCi) at screening, week 12 and week 24.

Drug: Pembrolizumab; Drug: 177Lu-PNT2002; Drug: (F-18)-DCFPyL

177Lu-PNT2002 6.8 GBq

EXPERIMENTAL

177Lu-PNT2002 administered at 6.8 GBq intravenously (IV) every 8 weeks combined with the standard dose of pembrolizumab 400 mg IV every 6 weeks. 18F-DCFPyL administered as a single bolus intravenous radioactive dose injection of 333 MBq (9 mCi) at screening, week 12 and week 24.

Drug: Pembrolizumab; Drug: 177Lu-PNT2002; Drug: (F-18)-DCFPyL

Dose Expansion

EXPERIMENTAL

177Lu-PNT2002 administered at the maximum tolerated dose (determined by the 3 dose levels in the dose escalation phase of the study) intravenously (IV) every 8 weeks combined with the standard dose of pembrolizumab 400 mg IV every 6 weeks. 18F-DCFPyL administered as a single bolus intravenous radioactive dose injection of 333 MBq (9 mCi) at screening, week 12 and week 24.

Drug: Pembrolizumab; Drug: 177Lu-PNT2002; Drug: (F-18)-DCFPyL

Interventions

Pembrolizumab DRUG

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.

Also known as: Keytruda

177Lu-PNT2002 3.4 GBq; 177Lu-PNT2002 5.1 GBq; 177Lu-PNT2002 6.8 GBq; Dose Expansion

177Lu-PNT2002 DRUG

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.

Also known as: 177Lu-PSMA I&T

177Lu-PNT2002 3.4 GBq; 177Lu-PNT2002 5.1 GBq; 177Lu-PNT2002 6.8 GBq; Dose Expansion

(F-18)-DCFPyL DRUG

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.

Also known as: Pylarify

177Lu-PNT2002 3.4 GBq; 177Lu-PNT2002 5.1 GBq; 177Lu-PNT2002 6.8 GBq; Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of clear cell RCC will be enrolled in this study.
• Participants must have progressed on treatment with an anti-PD-1/L1 ICI administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Treatment with at least 6 weeks of an approved anti-PD-1/L1 ICI.
• More than one prior line of anti-PD-1/L1 ICI is allowed.
• The immediate prior line of therapy is not mandated to be with anti-PD-1/L1 ICI.
• Postoperative or adjuvant systemic therapy can be counted as a prior ICI therapy as long as recurrence is detected within 6 months of completion of treatment, in which case it will be counted as a prior therapy for metastatic disease.
• Metastatic or locally advanced inoperable clear cell RCC.
• Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline.
• Evidence of positive PSMA avid lesions as per (F-18)-DCFPyL PSMA PET scan at screening. Positive lesions on PSMA-PET are defined as those with maximum standardized uptake value (SUVmax) values greater than liver as assessed by the local site investigator radiologist.
• At least 70% of all the following lesions must PSMA-PET positive:
• Lymph nodes that measure ≥ 25 mm in short axis on anatomic imaging.
• Bone metastasis with soft tissue component ≥ 10 mm in short axis.
• Solid organ metastasis ≥ 10 mm in short axis.
• A maximum of 4 prior lines of systemic therapy is allowed, including more than one line of ICI regimens.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 with a life expectancy ≥ 6 months

You may not qualify if:

• Renal cell carcinoma with non-clear cell histology.
• Prior exposure to radioligand therapy or radioisotope therapy.
• Treatment with RCC standard of care anti-cancer therapy within 14 days prior to initiation of study treatment
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• PSMA targeted imaging within 2 weeks prior to screening.
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-central nervous system diseases permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
• Must have recovered from any grade 3 or higher reversible toxicity to prior anti cancer therapy treatments.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has a diagnosis of immunodeficiency (e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV) or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and prostate-specific antigen (PSA) \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab or (F-18)-DCFPyL (Pylarify) and/or any of their components.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• Merck Sharp & Dohme LLC: collaborator
• Lantheus Medical Imaging: collaborator

MeSH Terms

Conditions

Carcinoma, Renal Cell; Clear-cell metastatic renal cell carcinoma; Kidney Neoplasms

Interventions

pembrolizumab; 2-(3-(1-carboxy-5-((6-fluoropyridine-3-carbonyl)amino)pentyl)ureido)pentanedioic acid

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Yasser Ged, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2024
• First Posted: April 12, 2024
• Study Start: October 1, 2025
• Primary Completion (Estimated): January 1, 2031
• Study Completion (Estimated): January 1, 2032
• Last Updated: August 19, 2025

Record last verified: 2025-08