Trial Title:
Pembrolizumab Plus 177Lu-PSMA-617 in Patients With Castration Resistant Prostate Cancer
NCT ID:
NCT05766371
Condition:
Castrate Resistant Prostate Cancer
Metastatic Castration-resistant Prostate Cancer
Prostate Cancer
Prostate Carcinoma
Conditions: Official terms:
Prostatic Neoplasms
Pembrolizumab
Pluvicto
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Given IV
Arm group label:
Pembrolizumab, 177Lu-PSMA-617
Other name:
Keytruda
Intervention type:
Drug
Intervention name:
177Lu-PSMA-617
Description:
Given IV
Arm group label:
Pembrolizumab, 177Lu-PSMA-617
Other name:
Lutetium-177-PSMA-617
Other name:
(177Lu)-PSMA-617
Summary:
This is a single-center, open-label, study of Prostate-Specific Membrane Antigen
(PSMA)-targeted radionuclide therapy with 177Lu-PSMA-617 in combination with
pembrolizumab in participants with metastatic castrate-resistant prostate cancer (mCRPC)
who have previously progressed on at least one prior androgen pathway inhibitor (e.g.,
abiraterone, enzalutamide, apalutamide).
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the 12-month radiographic progression-free survival rate per Response
Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and Prostate Cancer Clinical
Trials Working Group 3 (PCWG3) criteria in patients with mCRPC treated with pembrolizumab
and 177Lu-PSMA-617.
SECONDARY OBJECTIVES:
I. To determine the median radiographic progression-free survival per RECIST v. 1.1 and
PCWG3 criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.
II. To determine the objective response rate per RECIST v. 1.1 and PCWG3 criteria in
patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.
III. To determine the median duration of objective response per RECIST v. 1.1 and PCWG3
criteria in patients with mCRPC treated with pembrolizumab and 177Lu-PSMA-617.
IV. To determine the greater than 50% decline from baseline PSA (PSA50) and greater than
90% decline from baseline PSA (PSA90) response rate by PCWG3 criteria at any time point
on study, as well as individually following each dose of 177Lu-PSMA-617.
V. To determine the median time to PSA progression (TTPP) following each dose of
177Lu-PSMA-617 (e.g., TTPP-1, TTPP-2, etc.), as measured by PCWG3 criteria.
VI. To determine the median overall survival in patients with mCRPC treated with
pembrolizumab and 177Lu-PSMA-617.
VII. To characterize the safety profile of the combination of pembrolizumab and
177Lu-PSMA-617 in patients with mCRPC.
OUTLINE:
Participants will receive one dose of 177Lu-PSMA-617 and may continue treatment for up to
six total doses, in the absence of unequivocal clinical progression, or unacceptable
toxicity, with minimum interval of 6 weeks between doses. Participants will also receive
pembrolizumab and may continue study treatment until unequivocal evidence of clinical
progression or at physician's discretion based on clinical evaluation. Participants will
undergo safety follow-up visits approximately 30 days following the end of treatment
visit. After the last dose/discontinuation of study drug(s), participants will be seen in
clinic or contacted by telephone every 3 months after their last treatment date to assess
survival/disease/anti-cancer therapy status until death, withdrawal of consent, or the
end of the study, whichever occurs first.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed prostate adenocarcinoma that is progressive metastatic
castration-resistant prostate cancer by Prostate Cancer Clinical Trials Working
Group 3 (PCWG3) criteria at the time of study entry.
2. Male participants who are at least 18 years of age on the day of signing informed
consent.
3. Castrate level of serum testosterone at study entry (< 50 ng/dL). Note: Patients
without prior bilateral orchiectomy are required to remain on Luteinizing
hormone-releasing hormone (LHRH) analogue treatment for duration of study.
4. Have received at least one prior line of taxane chemotherapy, or are unfit for, or
refuse taxane chemotherapy. Note: Taxane chemotherapy administered in the Castration
Sensitive Prostate Cancer (CSPC) or Castration Resistant Prostate Cancer (CRPC)
setting is allowed.
5. Prior progression on at least one second generation androgen signaling inhibitor
including abiraterone, apalutamide, darolutamide, and/or enzalutamide.
6. Adverse events related to prior anti-cancer treatment (excluding LHRH analogs) must
have recovered to Grade <= 1 (except for any grade alopecia and grade <= 2
neuropathy).
7. Prior radiotherapy is allowed if the last radiotherapy treatment was greater than 2
weeks from start of study treatment on cycle 1, day 1 (C1D1). Note- Participants
must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is
permitted for palliative radiation (<=2 weeks of radiotherapy) to non-central
nervous system (CNS) disease.
8. At least one Prostate-Specific Membrane Antigen (PSMA) Positron Emission Tomography
(PET) (PSMA PET) avid lesion on screening PSMA PET. A positive lesion is defined as
uptake above background liver.
9. Eastern Cooperative Oncology Group (ECOG) performance status <= 1 (Karnofsky >=
70%).
10. Demonstrates adequate organ function as defined below:
1. Adequate bone marrow function:
- absolute neutrophil count >=1,500/microliter (mcL)
- platelets >=100,000/mcL
- hemoglobin > 9.0 g/dL
2. Adequate hepatic function:
- total bilirubin <= 1.5 x upper limit of normal (ULN). In patients with
known or suspected Gilbert's disease, direct bilirubin <= ULN
- aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase
(SGOT) <= 2.5 x institutional ULN (<= 5 x ULN in patients with liver
metastases)
- alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT)
<= 2.5 x institutional upper limit of normal (<= 5 x ULN in patients with
liver metastases)
3. Adequate renal function:
- creatinine <= 1.5 x within institutional upper limit of normal OR
- creatinine clearance Glomerular filtration rate (GFR) >= 50 mL/min/1.73
m^2, calculated using the Cockcroft-Gault equation or 24 hour urine
collection.
11. Patients must use appropriate methods of contraception during study treatment and
for at least 6 months after last study treatment. Patients who are sexually active
should consider their female partner to be of childbearing potential if she has
experienced menarche and is not postmenopausal (defined as amenorrhea > 24
consecutive months) or has not undergone successful surgical sterilization. Even
women who use contraceptive hormones (oral, implanted, or injected), an intrauterine
device, or barrier methods (diaphragms, condoms, spermicide) should be considered to
be of childbearing potential. Patients who have undergone vasectomy themselves
should also be considered to be of childbearing potential. Acceptable methods of
contraception include continuous total abstinence, or double-barrier method of birth
control (e.g., condoms used with spermicide, or condoms used with oral
contraceptives). Periodic abstinence and withdrawal are not acceptable methods of
contraception.
12. Patients must provide consent to comply to recommended radioprotection precautions
during study.
13. Patients willing to undergo tumor biopsy and have at least one lesion safely
accessible to tumor biopsy. Bone or soft tissue lesion is allowed.
14. Patients with previously treated brain metastases are eligible provided the
following criteria are all met:
1. Last treatment was > 28 days prior to C1D1.
2. No evidence of new/progressive brain metastases is observed on magnetic
resonance imaging (MRI) obtained during screening window
3. Patient is clinically stable without requirement of steroid treatment for at
least 14 days prior to first dose of study treatment on C1D1.
15. Individuals with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial.
16. Ability to understand and the willingness to sign a written informed consent
document.
Exclusion Criteria:
1. De novo small cell neuroendocrine prostate cancer will not be allowed due to
putative lower PSMA expression in this tumor subtype. Note-Treatment-emergent small
cell neuroendocrine prostate cancer detected in metastatic tumor biopsy is not
excluded.
2. Soft tissue lesions (lymph nodes > 1.5 centimeter (cm) in short axis, visceral/soft
tissue lesions > 1 cm) on screening Computerized tomography (CT) that are negative
on PSMA PET. Note: Negative lesions on PSMA PET are defined as those with uptake
below the background liver.
3. Has received other systemic anti-cancer therapies administered within 14 days, or 5
half-lives, whichever is shorter, prior to initiation of study treatment. Note: LHRH
analogues are the exception.
4. Untreated brain metastases at study entry.
5. Receipt of prior PSMA-directed treatment (e.g., radiotherapy, immunotherapy, or
antibody-drug conjugate).
6. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-Programmed cell
death-ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or
co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4
(CTLA-4), OX 40, CD137).
7. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose
of study treatment on C1D1. Note: Participants who have entered the follow-up phase
of an investigational study may participate as long as it has been 4 weeks after the
last dose of the previous investigational agent.
8. Receipt of > 2 lines of prior taxane-based chemotherapy.
9. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
10. Has an active autoimmune disease that has required systemic treatment in the past 2
years (i.e., with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency) or treatment with drugs (e.g., neomercazole, carbimazole, etc.) that
function to decrease the generation of thyroid hormone by a hyper-functioning
thyroid gland (e.g., in Graves' disease) is not considered a form of systemic
treatment of an autoimmune disease.
11. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy at a
prednisone equivalent dose of > 10 mg daily or other form of immunosuppressive
therapy within 7 days prior to first dose of study drug.
12. Has a history of (non-infectious) ≥ grade 2 pneumonitis/interstitial lung disease
that required steroids within past 2 years or has current ≥ grade 1 pneumonitis/
interstitial lung disease at the time of study enrollment.
13. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug on C1D1. Note-Administration of a killed vaccine is
allowed.
14. Patients who because of age, general medical or psychiatric condition, or
physiologic status cannot give valid informed consent.
15. Has clinically significant cardiovascular disease including, but not limited to:
1. Uncontrolled or any New York Heart Association Class 3 or 4 congestive heart
failure.
2. Uncontrolled angina, history of myocardial infarction, unstable angina, or
stroke within 6 months before study entry.
3. Clinically significant arrhythmias not controlled by medication. Note: Chronic
rate controlled or paroxysmal atrial fibrillation/flutter is not an exclusion
to study participation.
16. Prior external beam radiation involving > 25 percent (%) of bone marrow or within 14
days of start of protocol therapy on C1D1.
17. Major surgery within 28 days of study treatment. Note: If participant received major
surgery, they must have recovered adequately from the toxicity and/or complications
from the intervention prior to starting study treatment on C1D1. Minor procedures
(e.g., biopsy, cataract surgery, stent placement, endoscopy) are not considered
major surgery.
18. Has an active infection requiring intravenous antibiotics within 7 days prior to
C1D1.
19. Has a known history of human immunodeficiency virus (HIV) infection. Note: Screening
not required.
20. Has a known history of Hepatitis B infection (defined as Hepatitis B surface antigen
(HBsAg) reactive) or known active Hepatitis C virus infection (defined as (HCV RNA)
[qualitative] detected, with the following exceptions:
1. participants who are HbsAg positive are eligible if they have received
Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have
undetectable HBV viral load prior to study entry
2. participants with history of Hepatitis C virus (HCV) infection are eligible if
HCV viral load is undetectable at screening. Participants must have completed
curative anti-viral therapy at least 4 weeks prior to study entry.
21. Has a known history of active Bacillus Tuberculosis (TB).
22. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
23. History of bleeding diathesis and currently on anti-coagulation therapy that cannot
be safely discontinued for the tumor biopsy procedure.
24. Any condition that, in the opinion of the Principal Investigator, would impair the
participant's ability to comply with study procedures.
Gender:
Male
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco
Address:
City:
San Francisco
Zip:
94143
Country:
United States
Status:
Recruiting
Contact:
Last name:
UCSF Genitourinary Medical Oncology Recruitment
Phone:
877-827-3222
Email:
GUTrials@ucsf.edu
Contact backup:
Email:
cancertrials@ucsf.edu
Investigator:
Last name:
Rahul Aggarwal, MD
Email:
Principal Investigator
Start date:
December 15, 2023
Completion date:
May 31, 2031
Lead sponsor:
Agency:
University of California, San Francisco
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Collaborator:
Agency:
Prostate Cancer Foundation
Agency class:
Other
Source:
University of California, San Francisco
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05766371
