RO7656594 for Prostate Cancer

Recruiting at 38 trial locations

Overseen By GO44537 https://forpatients.roche.com/

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must be taking: AR-targeted therapy

Must not be taking: AR protein degrader

Disqualifiers: CNS metastases, Leptomeningeal disease, others

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

Compensation: Varies

Number of Visits: Unknown

210 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, RO7656594, for advanced prostate cancer that has spread. The main goal is to assess the treatment's safety and tolerability while determining the optimal dose for future studies. Individuals with metastatic prostate cancer who have not responded to certain therapies may qualify for this trial. Participants will receive the treatment in two stages: initially to establish a safe dose, and then to further evaluate its effects at that dose. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial requires that you stop taking any approved systemic anti-cancer therapy at least 14 days before starting the study treatment. If you're on an investigational agent, you need to stop it 28 days before. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that RO7656594 is likely to be safe for humans?

Researchers are investigating RO7656594 to determine its safety and tolerability. This early-phase trial aims to understand the body's reaction to the treatment and identify potential side effects. Detailed safety information from earlier studies is not yet available. However, early-phase trials typically involve close monitoring to establish a safe dose and ensure participant safety. This process helps identify potential issues before progressing to larger studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about RO7656594 because it offers a new approach to treating prostate cancer. Unlike traditional treatments such as hormone therapy, chemotherapy, or radiation that target cancer cells more broadly, RO7656594 is designed to be more specific in its action, potentially improving effectiveness and reducing side effects. This specificity could mean better outcomes for patients, as it aims to precisely attack cancer cells while sparing healthy tissue. By focusing on novel targets within prostate cancer cells, RO7656594 represents a promising step forward in cancer treatment.

What evidence suggests that RO7656594 might be an effective treatment for prostate cancer?

Research has shown that RO7656594 is being tested as a potential treatment for advanced prostate cancer. The trial consists of two stages: Stage 1 involves dose escalation to determine the appropriate dosage, while Stage 2 focuses on expansion at or below the maximum tolerated dose. This drug aims to block the pathways that cancer cells use to grow and spread. Early results suggest that RO7656594 might slow or stop cancer cell growth. The main goal is to assess the drug's safety and determine the right dose, but initial signs are promising, with some patients showing reduced tumor activity. Although more information is needed, the mechanism of this treatment offers hope for those with advanced prostate cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for men with advanced or metastatic prostate cancer who have already tried at least one second-generation hormone therapy and a taxane chemotherapy, unless they can't tolerate or refused the chemo. They should be relatively active and able to care for themselves (ECOG ≤1).

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

My prostate cancer has spread and is not small-cell or neuroendocrine type.

I have been treated with a specific prostate cancer medication before.

Exclusion Criteria

Treatment with any investigational agent within 28 days prior to the first study treatment

I have brain metastases or leptomeningeal disease that hasn't been treated.

I haven't had cancer treatment in the last 14 days or within the drug's elimination period.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive RO7656594 at increasing doses in 28-day cycles until a threshold is reached

Varies per cohort

Multiple visits per cycle

Expansion

Participants receive RO7656594 at or below the maximum tolerated dose

Up to 12 months

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• RO7656594

Trial Overview The study is testing RO7656594's safety, how it affects the body, and its effectiveness in treating prostate cancer. Participants will receive different doses of RO7656594 to find out what amount works best for future studies.

How Is the Trial Designed?

Group I: Stage 2: Expansion Experimental Treatment 1 Intervention

Participants will receive RO7656594 at or below the maximum tolerated dose (MTD) or maximum administered dose (MAD).

Group II: Stage 1: Dose Escalation Experimental Treatment 1 Intervention

Participants will receive RO7656594 administered at a specified dose on specific days in each 28-day cycle. The dose will be increased in successive cohorts until a study-specific threshold is reached.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

ROR2 expression is significantly lower in metastatic prostate cancer (PCa) compared to primary tumors, and low levels of ROR2 are associated with poorer survival and higher recurrence rates in patients.

Increasing ROR2 levels in PCa cells inhibits their migration and invasion by regulating the PIAS3-PI3K-AKT2 signaling pathway, suggesting that ROR2 could be a potential therapeutic target to prevent PCa metastasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROR2 suppresses metastasis of prostate cancer via regulation of miR-199a-5p-PIAS3-AKT2 signaling axis. Tseng, JC., Huang, SH., Lin, CY., et al.[2021]

The study identifies a novel mechanism by which the RON receptor in prostate cancer cells promotes castration-resistant prostate cancer (CRPC) through the recruitment of tumor-associated macrophages, which enhance cancer cell signaling.

Targeting both RON and macrophages in a mouse model showed potential to sensitize CRPC to androgen deprivation therapy (ADT), suggesting that combining macrophage-targeting agents with RON/Axl inhibition could improve treatment outcomes for patients with CRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate tumor RON receptor signaling mediates macrophage recruitment to drive androgen deprivation therapy resistance through Gas6-mediated Axl and RON signaling. Brown, NE., Jones, A., Hunt, BG., et al.[2023]

RORγ antagonists, such as XY018 and compound 31, effectively inhibit tumor growth in metastatic castration-resistant prostate cancer (mCRPC) models, including patient-derived xenografts, suggesting a new therapeutic avenue.

The study identifies a novel mechanism where RORγ and PBK interact to enhance androgen receptor signaling, and their dual inhibition shows synergistic effects in reducing cancer cell growth, highlighting a promising strategy for treating advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting Feedforward Loops Formed by Nuclear Receptor RORγ and Kinase PBK in mCRPC with Hyperactive AR Signaling. Zhang, X., Huang, Z., Wang, J., et al.[2022]

A meta-analysis of 15 randomized controlled trials involving 16,795 patients found that novel oral anti-androgens (NOAAs) are associated with a 26% increased risk of all-grade fatigue compared to standard treatments.

Interestingly, NOAAs were linked to a decreased risk of anemia, suggesting that while they may cause fatigue, they do not significantly increase the likelihood of anemia in patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Fatigue and Anemia in Patients With Prostate Cancer Treated With Novel Oral Anti-androgens: A Meta-Analysis of Randomized Controlled Trials. Babkoor, AA., Aljabri, Y., Alzubaidi, A., et al.[2022]

In the SPARTAN study, apalutamide combined with androgen deprivation therapy (ADT) led to rapid and significant reductions in prostate-specific antigen (PSA) levels in most patients, with 90% achieving at least a 50% reduction by 6 months, compared to only 1.5% in the placebo group.

Deep PSA responses (≥90% reduction or PSA ≤0.2 ng/ml) at 6 months were strongly linked to improved outcomes, including metastasis-free survival and overall survival, indicating that early PSA monitoring can be a valuable prognostic tool for patients with high-risk nonmetastatic castration-resistant prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Prostate-specific Antigen Response following Addition of Apalutamide to Ongoing Androgen Deprivation Therapy and Long-term Clinical Benefit in SPARTAN. Saad, F., Small, EJ., Feng, FY., et al.[2022]

Extended treatment with ODM-201, an androgen receptor antagonist, was well tolerated in 41 chemotherapy-naïve and CYP17 inhibitor-naïve patients with metastatic castration-resistant prostate cancer (mCRPC), showing an overall adverse event incidence of 80.5%, mostly mild (grade 1-2).

The treatment demonstrated sustained antitumour activity, with median times to prostate-specific antigen (PSA) progression of 12.4 months and radiological progression of 15.3 months, indicating that ODM-201 could be a viable long-term therapeutic option for mCRPC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumour Activity of ODM-201 (BAY-1841788) in Chemotherapy-naïve and CYP17 Inhibitor-naïve Patients: Follow-up from the ARADES and ARAFOR Trials. Shore, ND., Tammela, TL., Massard, C., et al.[2019]

ODM-201, a second-generation androgen receptor inhibitor, demonstrated similar pharmacokinetics between its tablet and capsule formulations, indicating that the tablet can be effectively used in treatment.

In a trial with 30 chemotherapy-naive men with metastatic castration-resistant prostate cancer, 83% showed a significant PSA response (≥50% reduction), and the treatment was well tolerated, with common side effects being fatigue and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: An Open-label Phase 1 Study. Massard, C., Penttinen, HM., Vjaters, E., et al.[2018]

ROR-γ is overexpressed in metastatic castration-resistant prostate cancer (CRPC) and drives the expression of the androgen receptor (AR), which is crucial for tumor growth.

Using ROR-γ antagonists not only reduces AR expression and its variant AR-V7 but also suppresses tumor growth in AR-expressing models and enhances the effectiveness of enzalutamide, showing potential as a new treatment strategy for advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ROR-γ drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Wang, J., Zou, JX., Xue, X., et al.[2023]

RORγ is identified as a promising therapeutic target in castration-resistant prostate cancer, as it is found to promote hyperactivity of the androgen receptor (AR) in this disease.

Using small-molecule antagonists to block RORγ effectively suppresses AR activity and slows tumor growth in mouse models, including those resistant to the antiandrogen enzalutamide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Therapeutic Target for Prostate Cancer. [2017]

The compound XY101, a RORγ inverse agonist, showed strong anti-prostate cancer activity with an IC50 value of 30 nM and effectively inhibited tumor growth in a mouse model.

XY101 demonstrated good oral bioavailability (59%) and a half-life of 7.3 hours, indicating its potential as a convenient and effective treatment option for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery and Characterization of XY101, a Potent, Selective, and Orally Bioavailable RORγ Inverse Agonist for Treatment of Castration-Resistant Prostate Cancer. Zhang, Y., Wu, X., Xue, X., et al.[2020]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05800665

NCT05800665 | A Study Evaluating the Safety, ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or ...

2. withpower.com withpower.com/trial/phase-1-prostatic-neoplasms-2-2023-a4770

RO7656594 for Prostate Cancer This trial is testing a new drug called RO7656594 to see if it is safe and effective for people with advanced prostate cancer.

3. trialx.com trialx.com/clinical-trials/listings/217894/a-study-evaluating-the-safety-pharmacokinetics-and-activity-of-ro7656594-in-participants-with-advanced-or-metastatic-prostate-cancer/?&geo_lat=-37.915&geo_lng=145.13&radius=10&place=Clayton&user_country=Australia

Clinical Research Trial Listing ( Metastatic Prostate Cancer The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or ...

4. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/prostate-cancer/a-study-evaluating-the-safety--pharmacokinetics--and-ac-41296.html

Clinical trial for Metastatic Prostate Cancer, Advanced P... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or ...

5. yalemedicine.org yalemedicine.org/clinical-trials/go44537-a-study-evaluating-the-safety-pharmacokinetics-and-activity-of-ro7656594-in-participants

A Phase 1, Open-Label, Multicenter, Dose-Escalation and ... The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary activity of RO7656594 in participants with advanced or ...

6. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/androgen-receptor-degrader-ro7656594?pn=1

Clinical Trials Using Androgen Receptor Degrader ... Trials 1-1 of 1. A Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7656594 In Participants With Advanced or Metastatic Prostate Cancer.