Metastatic Castration-resistant Prostate CancerPhase 1/2NCT05489991
A Study of TmPSMA-02 Chimeric Antigen Receptor (CAR) T-cells in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
A Phase 1/2 study testing TmPSMA-02 in people with Metastatic Castration-resistant Prostate Cancer, run by Tceleron Therapeutics, Inc. at 1 site in United States.
Trial summary
An open-label, multi-center, Phase 1/2 study to determine the safety, tolerability, and feasibility of dosing adult patients with mCRPC with genetically modified autologous T-cells (TmPSMA-02) engineered to express a CAR capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating… Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Metastatic Castration-resistant Prostate Cancer
- What is being tested?
- TmPSMA-02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Sep 2022to 3 May 2023
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults at least 18 years of age.
- A confirmed histologic diagnosis of prostate cancer.
- Castrate levels of testosterone (< 50 ng/dL).
- Measurable disease (radiographic or Prostate Specific Antigen [PSA]) per PCWG3 criteria (see Appendix 3)
- Received at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor (e.g., enzalutamide or apalutamide) or CYP17α inhibitor (e.g., abiraterone/ prednisone) and a taxane based regimen (e.g., docetaxel, cabazitaxel, etc). At least one line of prior therapy must be in the mCRPC setting. Note: Androgen deprivation therapy (ADT) with gonadotropin- releasing hormone (GnRH) agonist/antagonist does not count as a line of therapy nor does a first-generation nonsteroidal antiandrogen (e.g., bicalutamide, flutamide, etc.).
- Adequate vital organ function as defined by: (A) Estimated glomerular filtration rate (eGFR) eGFR ≥ 50 mL/min by Modification of Diet in Renal Disease criteria, (B) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 ULN. (C) Serum total bilirubin < 1.5 × ULN unless patient has known Gilbert's; if so, then serum bilirubin ≤ 3 mg/dL, or (D) Left ventricular ejection fraction ≥ 45%.
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- Patients must have adequate hematologic reserve and must not be dependent on transfusions to maintain these hematologic parameters. Adequate hematologic reserve is defined as: (A) Hemoglobin ≥ 8 g/dL, (B) absolute neutrophil count ≥ 1000/ μL, or (C) Platelet count ≥ 75,000/μL.
- Patients who have not undergone bilateral orchiectomy must be able to continue GnRH therapy during the study.
- Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
- Toxicities from any previous therapy must have recovered to Grade 1 or to the baseline. Exceptions include non-clinically significant toxicities as a result of previous therapy (e.g., alopecia, hormonal changes, weight loss, etc).
- Patients of reproductive potential agree to use protocol-specified highly effective contraceptive methods
Who cannot join
- Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening. [Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer may still be eligible], unless treated with curative intent, i.e., non-melanoma skin cancer.
- Prior treatment with autologous T-cell therapy. Note: Prior treatment with Sipuleucel-T is allowed.
- Patients who require chronic treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day). Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable.
- Prior allogeneic stem cell transplant.
- Active autoimmune disease (including, but not limited to, connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy. Patients should have stopped any immunosuppressive therapy within 6 weeks prior to Screening.
- Current infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV). Viral testing at Screening is required in all patients to rule out subclinical infections. Patients who are hepatitis B core antibody positive and hepatitis B surface antigen negative should have quantitative viral load measured. If viral load is undetectable, the patient may enroll and be monitored as per ASCO Guidelines.
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- Seizure disorder requiring anti-epileptic medications.
- History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients (e.g., human serum albumin, dimethyl sulfoxide [DMSO], dextran 40) that would preclude the patient safely receiving TmPSMA-02.
- History of or known predisposition to hemophagocytosis lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS)
- Any active infection currently being treated with antibiotics, anti-virals or anti-fungal. Prophylactic anti-microbials are not exclusionary.
- Active or recent (within the past 6 months prior to leukapheresis) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina or (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, (4) cerebrovascular accident.
- Active or uncontrolled medical or psychiatric condition that would preclude participation in the opinion of the Sponsor, Principal Investigator (PI) and/or their designee.
- Have inadequate venous access for or contraindications for the leukapheresis procedure. Central venous access is acceptable.
Trial locations and contacts
1 site in 1 country.
United States1 site
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
About this study
Official title: A Phase 1/2, Open-label, Multi-Center Study of Dually Armored Chimeric Antigen Receptor (CAR) T-cells (TmPSMA-02) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
An open-label, multi-center, Phase 1/2 study to determine the safety, tolerability, and feasibility of dosing adult patients with mCRPC with genetically modified autologous T-cells (TmPSMA-02) engineered to express a CAR capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T-cell.
Read the detailed description
This is a Phase 1/2 single-arm study designed to identify the dose and regimen of TmPSMA-02 that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with mCRPC.
The Phase 1 dose escalation portion of the study will employ a Bayesian Optimal Interval (BOIN) Design to define the Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D). Dose-limiting toxicities (DLTs) will be assessed from the start of LD regimen through 28-days post infusion of TmPSMA-02.
The Phase 2 portion will employ a Simon's 2-stage design and include a single-arm of adult patients with mCRPC treated with the TmPSMA-02 at the RP2D.
It is anticipated that up to 30 patients will enroll in the Phase 1 portion of the study and up to 84 patients will enroll in the Phase 2 portion of the study.
- Being tested
- TmPSMA-02
- Keywords
- Chimeric Antigen Receptor (CAR), T-Cells, Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TmPSMA-02Biological
Intravenous administration of genetically modified autologous T-cells engineered to express a protein capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) with a lentiviral vector to express anti-PSMA scFv, CD2 co-stimulatory domain and dually armored with a dominant negative TGFβ receptor and PD1.CD28 switch, will be infused intravenously on Day 0 as a single flat dose following standard lymphodepleting (LD) regimen.
| Study group | Role | What they receive |
|---|---|---|
| TmPSMA-02 | Experimental | Not described Receives: Biological: TmPSMA-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: To evaluate the safety of TmPSMA-02 in adult patients with mCRPC
Type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs)
Measured: Up to 5 years
Phase 1: To identify the recommended Phase 2 dose of TmPSMA-02 administered in combination with LD chemotherapy
Frequency of DLTs and/or determination of the maximum tolerated dose (MTD)
Measured: Up to 5 years
Phase 2: To evaluate the objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Objective Response Rate (ORR) by RECIST v1.1.
Measured: Up to 5 years
Secondary outcomes (6)
Phase 1: To evaluate the preliminary antitumor activity of TmPSMA-02 according to RECIST v1.1 and the PCWG3 criteria
Objective Response Rate (ORR), Duration of Response (DOR), PSA percent change from baseline at 12-weeks and maximal, change calculated at any timepoint Progression Free Survival (PFS) Radiographic progression free survival (rPFS) Overall Survival (OS)
Measured: Up to 5 years
Phase 1: To assess the clinical and manufacturing feasibility of TmPSMA-02
Clinical: proportion of patients enrolled on this protocol who do not receive TmPSMA-02 cells for any reasons not related to manufacturing (see below) Manufacturing: Proportion of patients whose leukapheresis product results in manufacturing failure for any reason
Measured: Up to 5 years
Phase 2: To evaluate the safety and tolerability of TmPSMA-02 in adult patients with mCRPC
Type, frequency, severity of AEs, SAEs
Measured: Up to 5 years
Phase 2: Evaluate the anti-tumor activity of TmPSMA-02 according to Prostate Cancer Working Group 3 (PCWG3).
Duration of Response (DOR), PSA percent change from baseline at 12-weeks and maximal change calculated at any timepoint, Progression Free Survival (PFS), Radiographic progression free survival (rPFS), Overall Survival (OS)
Measured: Up to 5 years
Phase 2: Describe pharmacokinetic factors of TmPSMA-02 in peripheral blood
Expansion and persistence of CAR T-cells by molecular detection of CAR-specific sequences in peripheral blood
Measured: Up to 5 years
Phase 2: Evaluate changes in patient reported health-related outcomes following treatment with TmPSMA-02
Evaluate changes in health-related outcomes following treatment with TmPSMA-02 using the Functional Assessment of Cancer Therapy - Prostate Cancer (FACT-P)
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2022
- Study start6 Sep 2022
- Primary completion3 May 2023
- Study completion3 May 2023
Why it stopped: Study was stopped Sponsor discretion. No patients were dosed.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration-resistant Prostate CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tceleron Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05489991
- Sponsor's protocol ID
- TmPSMA-0201
- Status last verified
- Aug 2023
- First submitted
- 22 Jul 2022
- Last updated
- 18 Aug 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Open-label, Multi-Center Study of Dually Armored Chimeric Antigen Receptor (CAR) T-cells (TmPSMA-02) in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)
- ClinicalTrials.gov ID
- NCT05489991
- Acronym / sponsor ID
- TmPSMA-0201
- Keywords
- Chimeric Antigen Receptor (CAR), T-Cells, Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped Sponsor discretion. No patients were dosed.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Tceleron Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Sep 2022 (actual)
- Primary completion
- 3 May 2023 (actual)
- Study completion
- 3 May 2023 (actual)
- First posted
- 5 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An open-label, multi-center, Phase 1/2 study to determine the safety, tolerability, and feasibility of dosing adult patients with mCRPC with genetically modified autologous T-cells (TmPSMA-02) engineered to express a CAR capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T-cell.
Detailed description
This is a Phase 1/2 single-arm study designed to identify the dose and regimen of TmPSMA-02 that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with mCRPC.
The Phase 1 dose escalation portion of the study will employ a Bayesian Optimal Interval (BOIN) Design to define the Maximum Tolerated Dose (MTD) and determine the Recommended Phase 2 Dose (RP2D). Dose-limiting toxicities (DLTs) will be assessed from the start of LD regimen through 28-days post infusion of TmPSMA-02.
The Phase 2 portion will employ a Simon's 2-stage design and include a single-arm of adult patients with mCRPC treated with the TmPSMA-02 at the RP2D.
It is anticipated that up to 30 patients will enroll in the Phase 1 portion of the study and up to 84 patients will enroll in the Phase 2 portion of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TmPSMA-02 | Experimental | Biological: TmPSMA-02 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adults at least 18 years of age.
- A confirmed histologic diagnosis of prostate cancer.
- Castrate levels of testosterone (< 50 ng/dL).
- Measurable disease (radiographic or Prostate Specific Antigen [PSA]) per PCWG3 criteria (see Appendix 3)
- Received at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor (e.g., enzalutamide or apalutamide) or CYP17α inhibitor (e.g., abiraterone/ prednisone) and a taxane based regimen (e.g., docetaxel, cabazitaxel, etc). At least one line of prior therapy must be in the mCRPC setting. Note: Androgen deprivation therapy (ADT) with gonadotropin- releasing hormone (GnRH) agonist/antagonist does not count as a line of therapy nor does a first-generation nonsteroidal antiandrogen (e.g., bicalutamide, flutamide, etc.).
Key exclusion criteria (13 listed)
- Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening. [Note: non-invasive cancers treated with curative intent (e.g., non-melanoma skin cancer may still be eligible], unless treated with curative intent, i.e., non-melanoma skin cancer.
- Prior treatment with autologous T-cell therapy. Note: Prior treatment with Sipuleucel-T is allowed.
- Patients who require chronic treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day). Low-dose physiologic replacement therapy with corticosteroids equivalent to prednisone 10 mg/day or lower, topical steroids and inhaled steroids are acceptable.
- Prior allogeneic stem cell transplant.
- Active autoimmune disease (including, but not limited to, connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy. Patients should have stopped any immunosuppressive therapy within 6 weeks prior to Screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TmPSMA-02Intravenous administration of genetically modified autologous T-cells engineered to express a protein capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) with a lentiviral vector to express anti-PSMA scFv, CD2 co-stimulatory domain and dually armored with a dominant negative TGFβ receptor and PD1.CD28 switch, will be infused intravenously on Day 0 as a single flat dose following standard lymphodepleting (LD) regimen. | Biological | TmPSMA-02 |
Primary outcome
Phase 1: To evaluate the safety of TmPSMA-02 in adult patients with mCRPC
Time frame: Up to 5 years
Type, frequency, and severity of adverse events (AEs) and serious adverse events (SAEs)
Phase 1: To identify the recommended Phase 2 dose of TmPSMA-02 administered in combination with LD chemotherapy
Time frame: Up to 5 years
Frequency of DLTs and/or determination of the maximum tolerated dose (MTD)
Phase 2: To evaluate the objective response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) v1.1
Time frame: Up to 5 years
Objective Response Rate (ORR) by RECIST v1.1.
6 secondary outcomes
Phase 1: To evaluate the preliminary antitumor activity of TmPSMA-02 according to RECIST v1.1 and the PCWG3 criteria
Time frame: Up to 5 years
Phase 1: To assess the clinical and manufacturing feasibility of TmPSMA-02
Time frame: Up to 5 years
Phase 2: To evaluate the safety and tolerability of TmPSMA-02 in adult patients with mCRPC
Time frame: Up to 5 years
Phase 2: Evaluate the anti-tumor activity of TmPSMA-02 according to Prostate Cancer Working Group 3 (PCWG3).
Time frame: Up to 5 years
Phase 2: Describe pharmacokinetic factors of TmPSMA-02 in peripheral blood
Time frame: Up to 5 years
Phase 2: Evaluate changes in patient reported health-related outcomes following treatment with TmPSMA-02
Time frame: Up to 5 years
Results and safety
The study was stopped early (reason given: Study was stopped Sponsor discretion. No patients were dosed.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TmPSMA-02 in people with Metastatic Castration-resistant Prostate Cancer, run by Tceleron Therapeutics, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was stopped Sponsor discretion. No patients were dosed.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: To evaluate the safety of TmPSMA-02 in adult patients with mCRPC (time frame: Up to 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Aug 2023.