Clinical Trial · NCT03805594

177Lu-PSMA-617 and Pembrolizumab in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

Overview

This phase Ib trial studies the dose and schedule of 177Lu-PSMA-617 and pembrolizumab in treating persons with castration-resistant prostate cancer that has spread to other places in the body. 177Lu-PSMA-617 carries a radioactive component which attached to the prostate specific membrane antigen (PSMA) receptor found on tumor cells. Its radiation component destroys the tumor cell. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving 177Lu-PSMA-617 and pembrolizumab may work better at treating prostate cancer.

Sponsor

University of California, San Francisco

Phase

Phase 1

Contacts

Rahul Aggarwal, MD (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT03805594

Drug / Compound

PSMA-11

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: HBED-CC

Linker: Ahx

PSMA-617

Isotope(s):

Target(s):

PSMA

Ligand Class: Small Molecules

Chelator: DOTA

Eligibility

Inclusion

Participants who have undergone vasectomy themselves should also be considered to be of childbearing potential
Aspartate aminotransferase and alanine aminotransferase =\< 2.5 x ULN (\<= 5 x ULN in participants with liver metastases)
Participants must use appropriate methods of contraception during study treatment and for at least 60 days after last study treatment
Hemoglobin \> 9.0 g/dL
Progressive metastatic castration-resistant prostate cancer by Prostate Cancer Working Group (PCWG)3 criteria at the time of study entry
Participants willing to undergo tumor biopsy and have at least one lesion safely accessible to tumor biopsy. Bone or soft tissue lesion is allowed
Total bilirubin =\< 1.5 x ULN. In participants with known or suspected Gilbert's disease, direct bilirubin =\< ULN
Absolute neutrophil count \> 1.5 x 10\^9/L
Prior progression on at least one second generation androgen signaling inhibitor including abiraterone, apalutamide, darolutamide, and/or enzalutamide
Platelet count \> 100,000/microliter
Serum creatinine =\< 1.5 x upper limit of normal (ULN) or estimated glomerular filtration rate (GFR) \> 50 ml/min by Cockcroft-Gault or 24 hour urine collection
Participants 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
Participants must provide consent to comply to recommended radioprotection precautions during study
A minimum of three PSMA-avid lesions on baseline 68Ga-PSMA-11 PET, with positive lesions defined as those with maximum standardized uptake value (SUVmax) values greater than liver.
No other systemic anti-cancer therapies administered other than LHRH analogue within 14 days, or 5 half-lives, whichever is shorter, prior to initiation of study treatment. Adverse events related to prior anti-cancer treatment other than LHRH analog treatment must have recovered to Grade \<= 1 with the exception of any grade alopecia and grade \<= 2 neuropathy.
Histologically confirmed prostate adenocarcinoma. De novo small cell neuroendocrine prostate cancer will not be allowed due to putative lower PSMA expression in this tumor subtype. Treatment-emergent small cell neuroendocrine prostate cancer detected in metastatic tumor biopsy is not an exclusion
Castrate level of serum testosterone at study entry (\< 50 ng/dL). Participants without prior bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue treatment for duration of study
Measurable disease by RECIST 1.1 criteria
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
Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Exclusion

Patient is clinically stable without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
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). 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 hyperfunctioning thyroid gland (e.g. in Graves? disease) is not considered a form of systemic treatment of an autoimmune disease
Receipt of taxane chemotherapy applied in the castration-resistant setting. Prior receipt of taxane chemotherapy in the hormone-sensitive setting is allowed
Has a known history of hepatitis B (defined as hepatitis B surface antigen \[HBsAg\] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid \[RNA\] \[qualitative\] is detected) infection (screening not required)
Prior external beam radiation involving \>= 25% of bone marrow or within 14 days of start of protocol therapy
History of bleeding diathesis and not currently on anti-coagulation therapy that cannot be safely discontinued for the tumor biopsy procedure
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients
Has an active infection requiring systemic therapy
No evidence of new/progressive brain metastases is observed on magnetic resonance imaging (MRI) obtained during screening window
Has a known history of human immunodeficiency virus (HIV) (screening not required)
Prior enrollment on clinical study investigating Lu-PSMA-based radioligand therapy
Untreated brain metastases at study entry. Participants with previously treated brain metastases are eligible provided the following criteria are all met:
Has received prior radiotherapy within 2 weeks of start of study treatment. 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
Receipt of prior PSMA-directed treatment (e.g. radiotherapy, immunotherapy, or antibody-drug conjugate)
Prior treatment with radium-223 or other radioisotope for the treatment of prostate cancer
Grade \> 2 peripheral neuropathy at the time of study entry
Last treatment was \> 28 days prior to cycle 1 day 1 (C1D1)
Receipt of prior pembrolizumab or another immune checkpoint inhibitor (e.g. nivolumab, ipilimumab)
Has a known history of active Bacillus tuberculosis (TB)
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
Uncontrolled angina, history of myocardial infarction, unstable angina or stroke within 6 months before study entry
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..
Clinically significant arrhythmias not controlled by medication. Chronic rate controlled or paroxysmal atrial fibrillation/flutter is not an exclusion to study participation
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
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
Any condition that, in the opinion of the principal investigator, would impair the patient's ability to comply with study procedures
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.
Has clinically significant cardiovascular disease including, but not limited to:
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
Uncontrolled or any New York Heart Association class 3 or 4 congestive heart failure