Cell Therapy + Enzalutamide for Prostate Cancer

Overseen By Fred Hutch Intake

Age: 18+

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Fred Hutchinson Cancer Center

Must be taking: Androgen inhibitors

Must not be taking: Immunosuppressants, Corticosteroids

Disqualifiers: Autoimmune disease, Uncontrolled infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

Duration: Up to 1 year

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for prostate cancer that continues to grow despite treatments and has spread to other parts of the body. It combines a type of cell therapy (STEAP1 CART), which uses modified immune cells to attack cancer cells, with enzalutamide, a drug that blocks male hormones to stop cancer growth. The goal is to determine if this combination is safe and more effective at killing cancer cells. The trial seeks men with prostate cancer that has become resistant to hormone treatments and has spread, especially those who have tried at least two other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot use other investigational anti-cancer agents during the trial, except for androgen deprivation therapy.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Earlier studies have shown that STEAP1 CART cell therapy is safe for people. Researchers found that it effectively targets prostate cancer cells without causing serious side effects, making it generally well-tolerated by those with advanced prostate cancer.

Another study demonstrated that enzalutamide helps prostate cancer patients live longer. The FDA has already approved this medication for treating prostate cancer, indicating its well-known safety profile. While side effects can occur, they are usually manageable.

Overall, both STEAP1 CART cell therapy and enzalutamide have shown safety in people, making them promising options for treating prostate cancer, especially when used together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for prostate cancer, which often include hormone therapy, chemotherapy, or radiation, STEAP1 CART uses a novel approach by employing CAR-T cell therapy. This treatment is unique because it genetically engineers a patient's own immune cells to specifically target and destroy cancer cells expressing the STEAP1 protein, potentially offering a more precise attack on cancer. Researchers are excited about STEAP1 CART because it represents a personalized and targeted strategy that could lead to better outcomes and fewer side effects compared to traditional therapies. Additionally, when combined with enzalutamide, a hormone therapy, there is potential for a synergistic effect that enhances the overall treatment efficacy.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will evaluate the combination of STEAP1 CART and enzalutamide for prostate cancer. Research has shown that STEAP1 CART may help target prostate cancer cells. In lab tests, these specially modified T-cells actively targeted prostate cancer and proved safe in human studies. Enzalutamide, a well-known treatment for advanced prostate cancer, has been proven to improve survival and slow cancer growth more effectively than some other treatments. Combining STEAP1 CART with enzalutamide might enhance the ability to kill cancer cells in patients with metastatic castration-resistant prostate cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

Rosa Nadal Rios, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for men with metastatic castration-resistant prostate cancer, which has spread beyond the prostate and resists treatment to lower male hormones. Participants must have tried hormone therapy and chemotherapy without success.

Inclusion Criteria

Fertile male participants and their female partners must be willing to use an effective contraceptive method before, during, and for at least 4 months after the STEAP1 CART cell infusion

My liver function tests, specifically AST and ALT, are within normal limits.

I have mild or no shortness of breath and my oxygen levels are above 92% without extra oxygen.

Exclusion Criteria

I am taking more than 15 mg of prednisone daily, but use it in short bursts for my condition.

I am not using any other experimental cancer treatments, except for hormone therapy to lower androgen levels.

My infections, including HIV or hepatitis, are well-controlled with medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Leukapheresis and Pre-treatment

Patients undergo leukapheresis and receive cyclophosphamide and fludarabine intravenously on days -5, -4, and -3

1 week

3 visits (in-person)

Treatment

Patients receive STEAP1 CART infusion on day 0 and may receive enzalutamide orally starting on day 0

Up to 1 year

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Regular visits at 2, 3, 4, 5, 6, 9, and 12 months, then every 6 months up to year 5, followed by yearly up to year 15

What Are the Treatments Tested in This Trial?

Interventions

• Enzalutamide
• STEAP1 CART

Trial Overview The trial tests STEAP1 CART cell therapy combined with enzalutamide, a drug blocking male hormones. It's checking if this combo can better target and kill prostate cancer cells that have spread and don't respond to usual treatments.

How Is the Trial Designed?

Group I: Treatment (STEAP1 CART, enzalutamide) Experimental Treatment 13 Interventions

Patients undergo leukapheresis then receive cyclophosphamide IV and fludarabine IV on days -5, -4 and -3 and STEAP1 CART IV on day 0. Patients may receive enzalutamide PO on day 0 then QD in the absence of disease progression or unacceptable toxicity. Patients also undergo a tumor biopsy at baseline, day 14 and optionally at progression. Patients additionally undergo blood sample collection, NM bone scan and CT scan, or MRI or PET scan throughout study. Additionally, patients may undergo ECHO or MUGA at screening.

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

PromiCell Therapeutics, Inc.

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

In a phase 3 trial involving 1401 men with nonmetastatic, castration-resistant prostate cancer, enzalutamide significantly improved median overall survival to 67.0 months compared to 56.3 months for placebo, indicating a 27% lower risk of death.

The safety profile of enzalutamide was consistent with previous studies, with a similar rate of serious adverse events compared to placebo, primarily involving fatigue and musculoskeletal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. Sternberg, CN., Fizazi, K., Saad, F., et al.[2021]

Enzalutamide (XTANDI) is an FDA-approved treatment for castration-resistant prostate cancer (CRPC) that effectively targets androgen receptor signaling, which is crucial for cancer progression.

In a Phase III clinical trial involving men with CRPC after chemotherapy, enzalutamide was well tolerated and significantly improved overall survival by 4.8 months, as indicated by reduced serum prostate-specific antigen (PSA) levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide: a novel anti-androgen with prolonged survival rate in CRPC patients. Dhingra, R., Sharma, T., Singh, S., et al.[2021]

Enzalutamide, when combined with a Twist-targeting immunotherapy, significantly improved overall survival in a mouse model of castration-resistant prostate cancer (CRPC), extending survival from 10.3 weeks to 27.5 weeks.

The study found that enzalutamide did not impair the immune response generated by the Twist vaccine, suggesting that this combination therapy could be a safe and effective strategy for treating advanced-stage prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with a second-generation androgen receptor antagonist and a metastasis vaccine improves survival in a spontaneous prostate cancer model. Ardiani, A., Farsaci, B., Rogers, CJ., et al.[2021]

In a long-term study of 67 patients with hormone-naïve prostate cancer, enzalutamide monotherapy resulted in a 100% prostate-specific antigen (PSA) response rate at 97 weeks for those who remained on treatment, indicating its strong efficacy.

The treatment was well-tolerated with minimal negative effects on total-body bone mineral density, although common side effects included gynecomastia and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Efficacy and Safety of Enzalutamide Monotherapy in Hormone-naïve Prostate Cancer: 1- and 2-Year Open-label Follow-up Results. Tombal, B., Borre, M., Rathenborg, P., et al.[2021]

The development of a CAR targeting STEAP1, which is found in about 90% of prostate cancers, shows promise as it effectively directs T cells to attack cancer cells while sparing normal tissues.

In mouse models, STEAP1 CAR T cells not only infiltrated tumors but also significantly inhibited tumor growth and improved survival, indicating strong potential for clinical application in treating prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of STEAP1 targeting chimeric antigen receptor for adoptive cell therapy against cancer. Jin, Y., Lorvik, KB., Jin, Y., et al.[2022]

The study identified STEAP2 as a promising target for CAR-T therapy in prostate cancer due to its high expression on tumor cells and limited presence in normal tissues, reducing the risk of off-target effects.

The engineered CAR-T therapy, AZD0754, showed strong anti-tumor activity in both laboratory and mouse models, demonstrating its potential as a safe and effective treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of AZD0754, a dnTGFβRII-armored, STEAP2-targeted CAR-T cell therapy, in prostate cancer. Zanvit, P., van Dyk, D., Fazenbaker, C., et al.[2023]

In a small phase I study involving 6 patients with metastatic castration-resistant prostate cancer (CRPC), the combination of entinostat and enzalutamide demonstrated a promising safety profile, with manageable side effects and no significant increase in fatigue.

Entinostat did not alter the plasma concentration of enzalutamide and showed biological activity by increasing histone H3 acetylation in peripheral blood mononuclear cells, suggesting potential mechanisms for its efficacy in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Study of Entinostat in Combination with Enzalutamide for Treatment of Patients with Metastatic Castration-Resistant Prostate Cancer. Lin, J., Elkon, J., Ricart, B., et al.[2021]

The PREVAIL Phase 3 trial demonstrated that enzalutamide significantly improves radiographic-progression free survival in men with castration-resistant prostate cancer (CRPC), with 65% of patients showing no progression compared to those on placebo.

Enzalutamide also provided a median overall survival benefit of 32.4 months versus 30.2 months for the placebo group, indicating its efficacy as a treatment option before chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enzalutamide for treatment of CRPC: rationale for sequencing and potential clinical biomarker for resistance. Lochrin, SE., Figg, WD., Finn, SP.[2020]

STEAP1 is a promising target for CAR T cell therapy in metastatic prostate cancer, showing effectiveness even at low antigen levels and demonstrating safety in preclinical models.

Combining STEAP1 CAR T cell therapy with a localized IL-12 treatment enhances the immune response against tumors, improving antitumor efficacy and addressing issues of treatment resistance due to STEAP1 antigen escape.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting advanced prostate cancer with STEAP1 chimeric antigen receptor T cell and tumor-localized IL-12 immunotherapy. Bhatia, V., Kamat, NV., Pariva, TE., et al.[2023]

In the SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved health-related quality of life (HRQoL) compared to placebo, with patients maintaining better scores over time.

Patients receiving apalutamide experienced minimal side effects and reported no worsening of fatigue, while those on placebo showed a decline in quality of life after about one year, highlighting the efficacy and tolerability of apalutamide in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy. Oudard, S., Hadaschik, B., Saad, F., et al.[2022]

The IMbassador250 trial involving 759 men with metastatic castration-resistant prostate cancer found that adding atezolizumab to enzalutamide did not improve overall survival, although it had an acceptable safety profile.

However, patients with high levels of PD-L1 expression and certain immune gene signatures showed longer progression-free survival, suggesting that careful patient selection could enhance the effectiveness of immune checkpoint inhibitors in this cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Powles, T., Yuen, KC., Gillessen, S., et al.[2023]

Citations

1. pfizer.com pfizer.com/news/press-release/press-release-detail/astellas-and-pfizers-xtanditm-enzalutamide-shows-long-term

Astellas and Pfizer's XTANDI™ (enzalutamide) Shows ... OS at 96 months was 50% with XTANDI and 40% for NSAA; progression-free survival (PFS) also favored XTANDI over NSAA (HR: 0.49; 95% CI, 0.42-0.57) ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2510310

Improved Survival with Enzalutamide in Biochemically ... In this trial, enzalutamide plus leuprolide led to significantly longer overall survival than leuprolide alone among patients with castration- ...

3. xtandihcp.com xtandihcp.com/cspc/efficacy

Efficacy CSPC | HCP Site | XTANDI® (enzalutamide) XTANDI (single agent) significantly improved metastasis-free survival vs placebo + GnRH therapy* · Number of events: 63 (17.7%) with XTANDI (single agent) vs 92 ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40660075/

The efficacy and safety of enzalutamide in metastatic ... Results: The data of 2275 patients were analyzed eventually. Enzalutamide reduced the risk of death by 33% compared to the control. Specifically ...

5. xtandi.com xtandi.com/clinical-trials

Clinical Trial Results | XTANDI® (enzalutamide) Men taking XTANDI had a 61% lower chance of their cancer progressing compared with men not taking XTANDI during the study. Progression was seen in 89 men (15.5 ...

6. pfizer.com pfizer.com/news/press-release/press-release-detail/xtandir-plus-leuprolide-reduced-risk-death-40-vs-leuprolide

XTANDI® Plus Leuprolide Reduced Risk of Death by 40% ... The probability of survival at 8 years was an unprecedented 78.9% with XTANDI plus leuprolide versus 69.5% with leuprolide, in men with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12504157/

Comparative effectiveness and safety of enzalutamide ... Effectiveness outcomes included all-cause death, prostate cancer-related death, and treatment failure. Safety outcomes included major adverse CV ...

8. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2833622

Enzalutamide and Prostate-Specific Antigen Levels in ... In this study, enzalutamide plus ADT was associated with improved outcomes in men with mHSPC regardless of pretreatment PSA level.