Vobramitamab Duocarmazine for Prostate Cancer

(Tamarack Trial)

No longer recruiting at 77 trial locations

Overseen By Global Trial Manager

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: MacroGenics

Must be taking: ARAT

Must not be taking: B7-H3 agents

Disqualifiers: CNS metastasis, BRCA/ATM mutation, 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: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vobramitamab duocarmazine for individuals with certain advanced cancers. The first part focuses on prostate cancer that has spread and continues to grow despite previous treatment with specific hormone therapies, known as Androgen Receptor Axis-Targeted therapies (ARAT), such as Abiraterone, Enzalutamide, Apalutamide, or Darolutamide. The second part examines other advanced solid tumors that have progressed after at least one round of chemotherapy. Suitable candidates might include those with prostate cancer who had prior hormone treatment or those with other solid tumors that have grown despite previous chemotherapy. The trial aims to determine the effectiveness and tolerability of the treatment for these conditions. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are using products known to decrease PSA or have anti-prostate cancer activity, you may need to stop those for Part 1 of the study.

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

Research has shown that vobramitamab duocarmazine, also known as MGC018, produced promising results in earlier studies. These studies found that the treatment helped fight tumors in patients with advanced prostate cancer. However, some patients experienced side effects, especially at higher doses of 3.0 mg/kg given every three weeks, which often led to early discontinuation of the treatment.

The current study tests different dosing schedules (2.0 mg/kg and 2.7 mg/kg every four weeks) to evaluate their safety and effectiveness. While specific safety data for these doses is not yet available, the ongoing research aims to find a balance where the treatment is both effective and easier to tolerate. The treatment remains experimental, and participants will be closely monitored for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about MGC018 for prostate cancer because it offers a novel approach compared to standard treatments like abiraterone and enzalutamide. MGC018 is an antibody-drug conjugate that specifically targets cancer cells, delivering a potent cytotoxic agent directly to them, potentially minimizing damage to healthy cells. This targeted mechanism of action could lead to more effective treatment outcomes with potentially fewer side effects, making it a promising option for patients with prostate cancer.

What evidence suggests that vobramitamab duocarmazine could be an effective treatment for prostate cancer?

Research has shown that vobramitamab duocarmazine, a treatment under study in this trial, may help treat advanced prostate cancer that has spread and resists standard hormone therapy. Studies have found that it can slow cancer growth, with some patients experiencing no progression for at least six months. In this trial, participants may receive vobramitamab duocarmazine at doses of 2.0 mg/kg or 2.7 mg/kg every four weeks. Early findings suggest that these lower doses are easier for patients to tolerate while remaining effective. This treatment targets B7-H3 proteins, often present in prostate cancer cells, to help stop cancer growth. These results offer hope for a new way to manage advanced prostate cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

Liudmila Schafer, M.D.

Principal Investigator

MacroGenics

Are You a Good Fit for This Trial?

Men with metastatic castration-resistant prostate cancer who've had one prior androgen receptor-targeted therapy and possibly one taxane regimen. They must have at least one detectable metastatic lesion, no neuroendocrine or small cell prostate cancer features, acceptable health status, and a tumor tissue sample if they have internal organ metastasis.

Inclusion Criteria

My prostate cancer is confirmed and does not show specific aggressive features.

I can provide a tissue sample from my cancer that has spread to an internal organ.

My cancer has worsened as shown by tests or scans.

Exclusion Criteria

I have had a stem cell, tissue, or organ transplant in the past.

Contradictions to the use of corticosteroid treatment

I have brain metastases that haven't been treated and are causing symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vobramitamab duocarmazine intravenously every 4 weeks until treatment discontinuation criteria are met

Up to 2 years

1 visit every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Every 8 weeks for the first 24 weeks, then every 12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ARAT
• MGC018

Trial Overview The trial is testing two doses of Vobramitamab Duocarmazine (2.0 mg/kg and 2.7 mg/kg) given every four weeks to see which works better for prostate cancer that has spread despite hormone therapy. Participants will be randomly assigned to either dose group in equal numbers.

How Is the Trial Designed?

Group I: Part 2 Experimental Treatment 1 Intervention

MGC018 2.7 mg/kg every 4 weeks

Group II: Part 1: MGC018 2.7 mg (Arm B) Experimental Treatment 1 Intervention

MGC018 2.7 mg/kg every 4 weeks

Group III: Part 1: MGC018 2.0 mg (Arm A) Experimental Treatment 1 Intervention

MGC018 2.0 mg/kg every 4 weeks

Group IV: Part 1: Control Arm Active Control 2 Interventions

Patients are administered abiraterone or enzalutamide

ARAT is already approved in United States, European Union, Japan, Canada for the following indications:

Approved in United States as Abiraterone for:

• Metastatic castration-resistant prostate cancer
• Metastatic castration-sensitive prostate cancer

Approved in European Union as Enzalutamide for:

• Metastatic castration-resistant prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in Japan as Apalutamide for:

• Metastatic castration-sensitive prostate cancer
• Non-metastatic castration-resistant prostate cancer

Approved in Canada as Darolutamide for:

• Non-metastatic castration-resistant prostate cancer

Who Is Running the Clinical Trial?

MacroGenics

Lead Sponsor

Trials

51

Recruited

5,400+

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03254-X/fulltext

1654P TAMARACK: Randomized Phase II trial of the B7- ... Phase 1 testing (NCT03729596) of vobra duo demonstrated anti-tumor activity in mCRPC, with adverse events at 3.0 mg/kg Q3W resulting in frequent early ...

2. macrogenics.com macrogenics.com/news/macrogenics-announces-updated-efficacy-safety-data-from-tamarack-phase-2-study-of-vobra-duo-in-mcrpc-patients-at-esmo-congress-2024/

MacroGenics Announces Updated Efficacy & Safety Data ... Encouraging antitumor activity demonstrated with vobra duo as measured by 6-month landmark rPFS rate and ORR; Patients remained on vobra duo ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05551117

NCT05551117 | A Study of Vobramitamab Duocarmazine ... This part of the study will assess the efficacy and tolerability of vobramitamab duocarmazine (MGC018) in two experimental arms (2.0 mg/kg every 4 weeks [Q4W] ...

4. urologytimes.com urologytimes.com/view/vobramitamab-duocarmazine-continues-to-show-promise-in-mcrpc

Vobramitamab duocarmazine continues to show promise ... Initial data from the study were reported in April 2024, showing that reduced dosing of vobra duo (to 2.0 mg/kg and 2.7 mg/kg) improved the ...

5. aacrjournals.org aacrjournals.org/cancerres/article/83/7_Supplement/2981/722746/Abstract-2981-Anti-tumor-activity-of-vobramitamab

Anti-tumor activity of vobramitamab duocarmazine (MGC018 ... MGC018 has shown preliminary clinical activity in B7-H3-expressing tumors, including castration-resistant metastatic prostate cancer.

6. fiercebiotech.com fiercebiotech.com/biotech/macrogenics-pulls-plug-vobra-duo-adc-after-seeing-phase-2-prostate-cancer-data

MacroGenics pulls plug on vobra duo ADC after seeing ... MacroGenics pulls plug on vobra duo ADC after seeing phase 2 prostate cancer data. By James Waldron Mar 21, 2025 7:15am.