A new generation of targeted drugs for treating advanced prostate cancer (PC) have come on the horizon. These drugs are referred to as antibody-drug conjugates or ADCs. 

The challenge with cancer treatment is ensuring that the benefits (effectiveness) of the treatment outweigh the risks (side effects). For example, chemotherapy kills cancer cells but doesn’t entirely differentiate between cancer cells and healthy cells. Chemotherapy can damage healthy cells too leading to side effects like hair-loss, tiredness, and heart toxicity. Monoclonal antibodies are capable of a more selective anti-cancer treatment.  ADCs combine the targeting power of antibodies and the advantages of chemotherapy. For patients this may mean potentially fewer side effects as the chemotherapy is preferentially delivered to the tumors with less chemotherapy delivered to normal tissues. 

There are 3 parts to ADCs:

1. Monoclonal Antibody: Targeted to a specific protein (B7-H3) on the surface of a cancer cell
2. Drug: A highly potent chemotherapy agent
3. Linker Molecule: Attached chemotherapy drug securely to the antibody breaking only when absorbed to the cancer cell. This lessens damage to healthy cells.

The primary objective of this study is to see how MGC018 (vobramitamab duocarmazine) performs in patients with mCRPC.

The Tamarack clinical trials are made up of two stages, Phase 2 and Phase 3:

• The Phase 2 stage will assess the efficacy (how well it works) and tolerability (monitoring side effects) of two doses of MGC018 compared to the control group (abiraterone or enzalutamide). 
• The Phase 3 stage will assess efficacy of the selected dose (determined during the phase 2 stage) of MGC018 group to that of the control (abiraterone for enzalutamide) group. 

Who can participate?

• Adults ≥ 18 years of age who have been diagnosed with advanced prostate cancer, called metastatic castration-resistant prostate cancer (mCRPC). This is a cancer that has spread beyond your prostate gland.
• To take part, you should have received:
  • Prior treatment with one Androgen Receptor Axis-targeted Therapy (ARAT) (abiraterone, enzalutamide, or apalutamide) with lack of progression for at least 12 months
  • Prior treatment with a taxane-containing regimen 

You will need to meet a few other criteria to take part in this study. The study team can explain these to you if you choose to learn more. 

Some key exclusion criteria include:

• Prior chemotherapy other than docetaxel or cabazitaxel. 
• Documented BRCA or ATM mutation (germline or somatic). 
  • Participants with known BRCA or ATM mutation who had disease progression or unacceptable toxicity on a PARP inhibitor ARE eligible.

The above is not an exhaustive list, for further information please speak to the study doctor.

What’s involved?

To see if you may qualify for the TAMARACK study, you will attend one or more screening visits at the study clinic. You will be asked health-related questions and will have several study assessments, tests, and procedures to help determine if the study is a good fit for you. 

TAMARACK Phase 2 Study:

If you are eligible, you will be randomly placed in either Group A, Group B, or Group C:

• Group A will receive Androgen Receptor Axis-targeted Therapy (ARAT) (abiraterone, enzalutamide, or apalutamide)
• Group B will receive MG018 2 mg/kg every 4 weeks
• Group C will receive MG018 2.7 mg/kg every 4 weeks

TAMARACK Phase 3 Study:

If you are eligible, you will be randomly placed in either Group A or Group B: 

• Group A will receive Androgen Receptor Axis-targeted Therapy (ARAT) (abiraterone, enzalutamide, or apalutamide)
• Group B will receive MG018 at the dose determined in the Phase 2 Study

Randomly assigning you to one of these groups helps avoid bias in the study. Researchers can learn about safety and effectiveness by comparing the experiences of people in the different groups.

Possible patient benefits

• This could slow and stop the progression of B7-H3 expressing prostate cancer and potentially prolong life as determined by X-ray analysis.
• Patients will be under close medical supervision for safety during the study period.

Possible Patient risks

THE USE OF MG018 DESCRIBED HERE IS INVESTIGATIONAL SAFETY AND EFFICACY HAVE NOT BEEN ESTABLISHED:

• The use of MGC018 may provide no benefit for preventing disease progression in these patients as compared to ARAT (Abiraterone or Enzalutamide).
• The use of MG018 may also cause side effects.

Clinical Trial Site:

Trials sites and contact can be found here.

Organization: MacroGenics
Email: info@macrogenics.com

If you are interested in this trial, review the following:

Clinicaltrials.gov Identifier: NCT05551117 

Use the “clinical trials glossary” and “dictionary” for words, phrases, and treatments that you may not understand.