Evofosfamide for Prostate Cancer

(EVO Trial)

Overseen By Alejandro Berlin, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must be taking: Castration therapy

Must not be taking: QT prolonging drugs, CYP3A4 inhibitors

Disqualifiers: Liver metastases, Brain metastases, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 9

Duration: Until disease progression or unacceptable toxicity

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests evofosfamide, a drug for prostate cancer that has spread and resisted first-line treatments. Researchers aim to determine if evofosfamide, combined with another existing treatment, can help when other therapies fail. The trial includes regular scans and check-ups to monitor progress and side effects. Men whose prostate cancer has worsened despite initial treatment, and who either progressed after or cannot have chemotherapy, might be suitable candidates. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop your current medications, but it mentions that participants must not take certain medications that affect the liver enzyme CYP3A4 within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that evofosfamide has been generally safe in earlier studies. In one study where evofosfamide was combined with another drug, researchers found no new or unexpected safety issues, indicating that the treatment was generally well-tolerated. Some side effects occurred, but they were expected and manageable. It's important to note that this trial is in an early phase, so researchers are still learning about its safety. However, the absence of surprising problems so far is a positive sign. ^{1 2 3 4 5}

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

Unlike the standard treatments for metastatic castration-resistant prostate cancer (M1 CRPC), which primarily involve androgen receptor signaling inhibitors (ARSIs), evofosfamide offers a unique approach. Evofosfamide is a hypoxia-activated prodrug, which means it becomes active in low-oxygen environments, like those often found in tumors. This targeted activation minimizes damage to healthy tissues and maximizes its cancer-fighting effects. Researchers are excited about evofosfamide because it has the potential to enhance the effectiveness of existing treatments by attacking cancer cells in a way that other drugs don't, especially in combination with an alternate ARSI. This novel mechanism could lead to more effective and less toxic treatment options for patients.

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

Research has shown that evofosfamide targets low-oxygen areas in tumors, known as hypoxia, which can help the immune system attack cancer cells more effectively. One study found that 17% of patients responded to treatment, and 83% had their disease controlled when evofosfamide was combined with other treatments. In this trial, participants will receive evofosfamide with an alternate ARSI. By reducing hypoxia, evofosfamide may also enhance the effectiveness of other therapies, such as immune checkpoint inhibitors, which help the immune system identify and fight cancer cells. This makes evofosfamide a promising option for prostate cancer that does not respond to initial treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for men with metastatic castrate-resistant prostate cancer (M1 CRPC) who have not responded to first-line ARSI treatments. Candidates should be ineligible for or have progressed after second-line Docetaxel therapy. They must undergo baseline molecular imaging and are encouraged to biopsy a dominant lesion before starting the study.

Inclusion Criteria

Ability to understand the purposes and risks of the trial and has signed a written ICF approved by the investigator's REB

My prostate cancer has spread and shows on scans.

My cancer progressed after initial hormone therapy and chemotherapy.

Exclusion Criteria

I am allergic to compounds similar to evofosfamide or its ingredients.

I am on medication that affects my heart's rhythm.

I have an active hepatitis B or C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging and Biopsy

Baseline molecular imaging (PSMA and FDG PET/CT) and optional biopsy of a dominant lesion

1-2 weeks

1 visit (in-person)

Treatment

Participants receive alternate ARSI and evofosfamide at a dose of 480 mg/m2 IV on Days 1, 8, and 15 of every 28-day cycle

Until disease progression or unacceptable toxicity

Monthly visits (in-person) for assessments

Follow-up

Participants are monitored for survival endpoints following completion of study treatment until death

Until death

Every 8 weeks (± 3 days) for assessments

What Are the Treatments Tested in This Trial?

Interventions

• Evofosfamide

Trial Overview The trial tests evofosfamide combined with an alternate ARSI treatment in patients who failed first-line ARSIs. Evofosfamide is given intravenously on specific days of a 28-day cycle, continuing until disease progression, unacceptable toxicity, or withdrawal by the subject.

How Is the Trial Designed?

Group I: Evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs Experimental Treatment 1 Intervention

After baseline molecular imaging (PSMA and fluorodeoxyglucose (FDG) PET/CT), prior to evofosfamide initiation, subjects will be encouraged to undergo biopsy of a dominant lesion: FDG-, PSMA-uptake and/or conventional imaging determined (in order, and according to feasibility). Subjects will then receive the alternate ARSI (i.e., different from the one received in first line) as per current standard practice and Provincial drug plan coverage. Additionally, subjects will receive combinatorial evofosfamide at a dose of 480 mg/m2 intravenously (IV) over 60 minutes on Days 1, 8 and 15 of every 28-day cycle. Therapy will continue until disease progression, unacceptable toxicity as a result of evofosfamide, or subject withdrawal. Assessments during evofosfamide treatment will include history, physical exam, and blood tests at each monthly visit to monitor for toxicity. Subjects will be followed for survival endpoints following completion of this study treatment until death.

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

ImmunoGenesis

Industry Sponsor

Trials

3

Recruited

210+

Citations

1. targetedonc.com targetedonc.com/view/evofosfamide-trial-targets-hypoxia-in-resistant-solid-tumors

Evofosfamide Trial Targets Hypoxia in Resistant Solid ... By reversing hypoxia, [evofosfamide] may restore T-cell access to tumors, enhancing the effectiveness of checkpoint inhibitors and potentially ...

2. withpower.com withpower.com/trial/phase-2-castration-resistant-prostate-cancer-3-2025-82548

Evofosfamide for Prostate Cancer · Info for Participants This is a single-institution, single-arm, open-label Phase 2 trial evaluating evofosfamide in subjects with M1 CRPC who fail first-line ARSIs.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8172466/

A Phase I Dose Escalation Study to Evaluate the Safety ... This Phase I study evaluated the safety and efficacy of combining hypoxia reduction (through evofosfamide) with blockade of the immune checkpoint (through ...

4. immunogenesis.com immunogenesis.com/acquisition-strengthens-cold-tumor-targeting-pipeline/

Acquisition Strengthens “Cold” Tumor Targeting Pipeline The combination treatment drove an overall response rate of 17 percent and a disease control rate of 83 percent across four different dose ...

5. mdpi.com mdpi.com/2072-6694/16/1/83

Exploiting the DNA Damage Response for Prostate Cancer ... ... Evofosfamide. Together, these data suggest that OC2 expression in CRPC-NE may serve as a marker for the use of treatments that take advantage of HAPs and ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40506027/

Efficacy and Safety of Ifosfamide and Mesna in Metastatic ... Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1558767319303921

Treatment Patterns and Outcomes in Patients With ... Using electronic health record data from the Flatiron Health database, we studied real-world treatment patterns and health outcomes in patients with mCRPC.