MacroGenics (MGNX) Study Update summary

Study design and patient population

• TAMARACK is a phase II study evaluating vobra duo (vobramitamab duocarmazine) in metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with one ARAT and up to one prior taxane regimen; 181 patients were enrolled, with 176 receiving at least one dose in two dosing cohorts (2.0 mg/kg and 2.7 mg/kg every four weeks).

• Patients were randomized 1:1; baseline characteristics were balanced except for a slight difference in ECOG status.

• The study aimed to improve safety and treatment duration compared to Phase 1 by reducing starting dose and increasing dosing interval.

• Primary endpoint was radiographic progression-free survival (rPFS); secondary endpoints included safety, PSA outcomes, ORR, DOR, and pharmacokinetics.

• Data cutoff for analysis was July 9, 2024.

Efficacy results

• Six-month landmark rPFS rates were 69% (2.0 mg/kg) and 70% (2.7 mg/kg); median rPFS was 8.5 months (2.0 mg/kg) and 7.5 months (2.7 mg/kg), with results still maturing.

• Confirmed objective response rates (ORR) were 20% (2.0 mg/kg) and 40.6% (2.7 mg/kg); including unconfirmed responses, ORRs were 26.7% and 46.9%, respectively.

• PSA50 response rates were 45.1% (2.0 mg/kg) and 39.4% (2.7 mg/kg) confirmed; higher when including unconfirmed responses.

• ORR was similar between taxane-naïve and taxane pre-treated patients, and tumor responses did not correlate with baseline B7-H3 expression.

• Duration of therapy improved compared to Phase 1, with median number of doses increased from 4 to 6.

Safety and tolerability

• Eight fatal treatment-related adverse events occurred: five in 2.0 mg/kg and three in 2.7 mg/kg cohorts, including pneumonitis and cardiac events.

• Most common adverse events (≥10% incidence) were asthenia, peripheral edema, nausea, decreased appetite, pleural effusion, diarrhea, and fatigue, mostly grade 1 or 2.

• Grade ≥3 treatment-related AEs were 46.7% (2.0 mg/kg) and 52.3% (2.7 mg/kg), lower than 78% in Phase 1; discontinuation rates due to TEAEs were 25.6% (2.0 mg/kg) and 38.4% (2.7 mg/kg).

• Lower rates of pleural effusion, pericardial effusion, and PPE syndrome were observed compared to Phase 1, especially in the 2.0 mg/kg arm.

• Dose reductions, increased dosing intervals, and other strategies are being considered to further improve safety.