Autologous Gamma Delta T Cells to Target Prostate Stem Cell Antigen in mCRPC

• ClinicalTrials.gov Identifier: NCT06193486
• Recruitment Status: Recruiting
• First Posted: January 5, 2024
• Last Update Posted: March 13, 2024
• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Information provided by (Responsible Party): H. Lee Moffitt Cancer Center and Research Institute

Study Description

Brief Summary:

This is a phase 1 single center clinical trial for patients with end stage Metastatic Castration Resistant Prostate Cancer who have progressed through standard of care treatment options and are on zoledronate for bone metastases. This clinical trial includes a dose-escalation phase and dose-expansion phase to assess the safety and preliminary efficacy of treatment with autologous T cells genetically modified to express Prostate stem cell antigen.

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer	Biological: MSGV1-PSCA-8T28Z; Drug: Fludarabine; Drug: Cyclophosphamide	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Clinical Trial of an Infusion of Autologous Gamma Delta T Cells Genetically Engineered With a Chimeric Receptor to Target the Prostate Stem Cell Antigen in Patients With Metastatic Castration Resistant Prostate Cancer
• Actual Study Start Date: February 26, 2024
• Estimated Primary Completion Date: January 13, 2029
• Estimated Study Completion Date: December 13, 2033

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dose Escalation; Participants will undergo leukapheresis followed by lymphodepletion and infusion of MSGV1-PSCA-8T28Z. The lymphodepletion regimen includes cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) administered over 3 days (Days -5, -4, -3). The standard "3+3" design will be used to guide dose escalation/de-escalation decisions based on the cumulative number of patients who experience a dose limiting toxicity (DLT) at the current dose. The first cohort of 3 patients will be treated at dose level 1. The target maximum doses infused at each dose level is: Dose Level 1: 1x10^5 cells/kg Dose Level 2: 3x10^5 cells/kg Dose Level 3: 1x10^6 cells/kg Dose Level 4: 3x10^6 cells/kg Dose Level 5: 1x10^6 cells/kg	Biological: MSGV1-PSCA-8T28Z; Autologous Gamma Delta T Cells Genetically Engineered with a Chimeric Receptor to Target the Prostate Stem Cell Antigen.; Drug: Fludarabine; Fludarabine is an antimetabolite given prior to lymphodepletion.; Other Name: Fludara; Drug: Cyclophosphamide; Cyclophosphamide is a nitrogen mustard-derivative, polyfunctional alkylating agent given prior to lymphodepletion.
Experimental: Dose Expansion; Participants will undergo leukapheresis followed by lymphodepletion and infusion of MSGV1-PSCA-8T28Z. Lymphodepletion will include 3 days of treatment with fludarabine (30 mg/m^2) and cyclophosphamide (500 mg/m^2) prior to study day 0. Participants will then receive MSGV1-PSCA-8T28Z at the dose level determined to be the Maximum Tolerated Dose (MTD) in the dose escalation portion of the study.	Biological: MSGV1-PSCA-8T28Z; Autologous Gamma Delta T Cells Genetically Engineered with a Chimeric Receptor to Target the Prostate Stem Cell Antigen.; Drug: Fludarabine; Fludarabine is an antimetabolite given prior to lymphodepletion.; Other Name: Fludara; Drug: Cyclophosphamide; Cyclophosphamide is a nitrogen mustard-derivative, polyfunctional alkylating agent given prior to lymphodepletion.

Outcome Measures

Primary Outcome Measures :

1. Maximum Tolerated Dose (MTD) of MSGV1-PSCA-8T28Z [ Time Frame: Up to 30 days post transplant ]
   MTD of MSGV1-PSCA-8T28Z based on Dose Limiting Toxicity (DLT) in patients with Metastatic Castration-Resistant Prostate Cancer.

Secondary Outcome Measures :

1. Best Prostate Specific Antigen (PSA) Response rate [ Time Frame: Up to 5 years ]
   Best PSA Response rate, which will be measured by percentage of patients who had 50% decline in PSA.
2. Radiographic progression-free survival (rPFS) [ Time Frame: Up to 5 years ]
   rPFS is defined as the duration of time from start of treatment to time of progression or death.
3. Percentage of circulating tumor cell count conversion from above 5/ml to below 5/ml. [ Time Frame: Up to 5 years ]
   The Circulating tumor cell conversion rate from above 5 to less than 5 will be used as a response criteria.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Men with metastatic castration-resistant prostate cancer (CRPC) to the bone with evidence of imaging progression based on the PCWG3 criteria.
• Prior therapies with at least 2 lines of chemotherapy and one new androgen receptor targeted therapy (abiraterone, enzalutamide, apalutamide, or darolutamide).
• For patients who are on zoledronic acid a booster dose of zoledronic acid is required if the last dose of zoledronic acid is >4 weeks prior to lymphodepletion chemo. If a patient is receiving denosumab, the next dose of denosumab needs to be changed to zoledronic acid and he needs to receive at least 1 dose of zoledronic acid prior to lymphodepletion chemotherapy. If a patient is not on zoledronic acid or denosumab, he needs to receive at least 2 doses of every 4 weeks of zoledronic acid prior to lymphodepletion chemotherapy. Zoledronic acid is recommended not to be resumed prior to week 8. After week 8, the resumption of zoledronic acid and the subsequent zoledronic acid treatment will be at the discretion of the treating physician.
• No anticancer therapy (chemotherapy, biologic therapy, radiation or immunotherapy) in the 3 weeks before the T cell infusion (and all hematologic effects have resolved). No prior treatment with Radium 223 or Puvicto within 3 months of T cell infusion. No prior immunotherapy with checkpoint blockade (e.g., PD-1 inhibitor, PDL1 inhibitor, or CTL4- antagonist or similar agent) in the 6 months before the T cell infusion (and all clinically significant related side effects must be resolved).
• Males age 18 years or older.
• ECOG performance status less than or equal to 2 (or Karnofsky Performance Status greater than or equal to 70%).
• Participants must have adequate organ and marrow function as defined by the protocol.
• Life expectancy of at least 6 months.
• The effects of CAR T cell infusion on the developing human fetus are unknown. Although patients who are eligible for this study will not have childbearing potential, any patient the treating doctor or investigator deems to have child fathering potential must agree to use adequate contraception from the time of screening to at least 6 months after administration of gamma delta enriched T cell infusion. Any female partner(s) with childbearing potential, of these participants, should also use adequate contraception during the same time period.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Known active hepatitis B infection, known history of hepatitis C or HIV infection.
• Known dental issues like osteonecrosis of jaw that excludes the use of zoledronic acid
• Any of the following cardiac conditions: Clinically significant heart disease (New York Heart Association class 3 or 4) or symptomatic congestive heart failure, Myocardial infarction less than 6 months before enrollment, History of clinically significant ventricular arrhythmia or unexplained syncope that is not believed to be vasovagal in nature or due to dehydration, History of severe non-ischemic cardiomyopathy with ejection fraction less than 20%, or Findings on baseline ECG or ECHO that, in the opinion of the patient's treating physician or investigator, would require medical intervention before anticancer therapy
• Active autoimmune disease (excluding autoimmune thyroid disease on a stable thyroid regimen). Such conditions include but are not limited to systemic lupus erythematous, rheumatoid arthritis, ulcerative colitis, Crohn's disease, and temporal arteritis.
• Known or suspected leptomeningeal disease and patients with metastases to the brain stem, midbrain, pons, or medulla.
• Known or suspected untreated brain metastases. Patients with radiographically stable, asymptomatic previously irradiated lesions are eligible provided patient is greater than 4 weeks beyond completion of cranial irradiation and greater than 3 weeks off of corticosteroid therapy at the time of study intervention.
• Prior history of clinically significant seizure disorder (e.g., not including childhood febrile seizures).
• Any concurrent active malignancies, defined as malignancies requiring any therapy other than expectant observation, because adverse events (AEs) resulting from these malignancies, or their treatment may confound our assessment of the safety of adoptive T cell therapy for ovarian cancer.
• Any of the following within 28 days of first date of study treatment: Serious uncontrolled medical illness or disorder that in the opinion of the treating physician would make the patient ineligible for the study, or Active uncontrolled infection (with the exception of uncomplicated urinary tract infection)
• Prior history of pancreatitis.
• Any other issue which, in the opinion of the treating physician or principal investigator, would make the patient ineligible for the study.

Contacts and Locations

Locations

United States, Florida

Moffitt Cancer Center; Recruiting

Tampa, Florida, United States, 33612

Contact: Tanner Pearson 813-745-6552 Tanner.Pearson@moffitt.org

Principal Investigator: Jingsong Zhang, MD, PhD

Sub-Investigator: Daniel Abate-Daga, PhD

Sub-Investigator: Juskaran Chadha, PhD

Sub-Investigator: Jad Chahoud, MD

Sub-Investigator: Monica Chatwal, MD

Sub-Investigator: Rohit Jain, MD

Principal Investigator: Daniel Abate-Daga, MD,PhD

Sponsors and Collaborators

H. Lee Moffitt Cancer Center and Research Institute

Investigators

• Principal Investigator: Jingsong Zhang, MD, PhD; Moffitt Cancer Center
• Principal Investigator: Daniel Abate-Daga, MD, PhD; Moffitt Cancer Center

More Information

Additional Information:

Related Info 

• Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
• ClinicalTrials.gov Identifier: NCT06193486
• Other Study ID Numbers: MCC-22344
• First Posted: January 5, 2024
• Last Update Posted: March 13, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Cyclophosphamide; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists