MacroGenics (MGNX) Study Update summary

Study design and patient population

• TAMARACK is a phase II study evaluating vobra duo (vobramitamab duocarmazine) in mCRPC patients previously treated with ARAT, with or without prior taxane therapy; 181 patients enrolled, 176 received at least one dose, randomized to 2.0 mg/kg or 2.7 mg/kg every four weeks.

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

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

• Both arms were well-balanced in baseline characteristics, except for a slight difference in ECOG status.

• Data cutoff for analysis was July 9, 2024.

Efficacy results

• Six-month landmark rPFS rate was 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 ORR was 20% (2.0 mg/kg) and 40.6% (2.7 mg/kg); including unconfirmed responses, ORR was higher.

• 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; tumor responses did not correlate with baseline B7-H3 expression.

• Efficacy results are consistent with prior interim data, and mature rPFS data are expected by early 2025.

Safety and tolerability

• Overall safety improved versus Phase 1; 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.

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

• Eight fatal treatment-related AEs occurred: pneumonitis (3), cardiac events, pleural effusion, GI hemorrhage, and others.

• Discontinuation rates due to TEAEs: 25.6% (2.0 mg/kg) and 38.4% (2.7 mg/kg); dose reductions and interruptions were common but less than in Phase 1.

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