MacroGenics' Vobra Duo Shows Promise in Metastatic Castration-Resistant Prostate Cancer
Key Insights
MacroGenics announced updated Phase 2 TAMARACK study data, showcasing vobramitamab duocarmazine's (vobra duo) encouraging antitumor activity in metastatic castration-resistant prostate cancer (search) (mCRPC (search)).
The study demonstrated a 6-month landmark radiographic progression-free survival (rPFS) rate of approximately 69-70% across both tested doses of vobra duo.
Vobra duo treatment was extended through a median of 6 doses, improving safety and tolerability compared to the Phase 1 mCRPC (search) dose expansion cohort.
MacroGenics, Inc. presented updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine (vobra duo) at the European Society for Medical Oncology (ESMO) Congress. The antibody-drug conjugate (ADC) targeting B7-H3 (search) is being evaluated in patients with metastatic castration-resistant prostate cancer (search) (mCRPC (search)). The data, with a cut-off date of July 9, 2024, demonstrated encouraging antitumor activity and improved tolerability compared to earlier studies.
The TAMARACK trial enrolled 181 participants, with 176 receiving at least one dose of vobra duo at either 2.0 mg/kg q4W (n=90) or 2.7 mg/kg q4W (n=86). As of the data cut-off, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. The primary endpoint was the landmark 6-month radiographic progression-free survival (rPFS) rate.
Efficacy Outcomes
The intent-to-treat (ITT) population showed a 6-month rPFS rate of 69% (95% CI, 57-79) for the 2.0 mg/kg arm and 70% (95% CI, 58-79) for the 2.7 mg/kg arm. These rates were consistent across both taxane-naïve (66-82%) and taxane pre-treated (60-73%) subgroups. Although the median rPFS data was immature, with only 65 PFS events (35.9%), it was approximately 8.5 months (95% CI, 7.2-11.2) for the 2.0 mg/kg cohort and 7.5 months (95% CI, 7.2-10.6) for the 2.7 mg/kg cohort.
Tumor response rates were also evaluated. In the 2.0 mg/kg arm, the confirmed objective response rate (ORR) was 20.0% (n=9/45), while the unconfirmed ORR was 26.7% (n=12/45). The 2.7 mg/kg arm showed a confirmed ORR of 40.6% (n=13/32) and an unconfirmed ORR of 46.9% (n=15/32). Confirmed ORR was comparable between taxane-naïve (26.7%) and taxane pre-treated (17.5%) participants.
Safety and Tolerability
The safety profile of vobra duo was also assessed. In the 2.0 mg/kg cohort, 65.6% of participants (n=59) experienced a Grade ≥3 treatment-emergent adverse event (TEAE), with a discontinuation rate of 25.6% (n=23) and a dose reduction rate of 50.0% (n=45) due to TEAEs. The 2.7 mg/kg cohort had 62.8% of participants (n=54) experiencing a Grade ≥3 TEAE, a discontinuation rate of 38.4% (n=33), and a dose reduction rate of 54.7% (n=47).
Common all-grade TEAEs (≥20% incidence) included asthenia, peripheral edema, decreased appetite, nausea, pleural effusion, diarrhea, fatigue, constipation, anemia, palmar-plantar erythrodysesthesia (PPE), neutropenia, and stomatitis. Notably, rates of pleural effusion, pericardial effusion, and PPE decreased compared to the Phase 1 mCRPC (search) dose expansion cohort, despite an increased median number of doses administered.
Eight fatal treatment-related AEs were reported, including pneumonitis, cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage.
Future Directions
Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics, stated, “We believe that these latest results from TAMARACK continue to demonstrate that vobra duo is an active drug in prostate cancer (search). Ultimately, our path forward for the molecule will depend on the final safety and efficacy data, including mature median rPFS, which we expect to have in hand no later than early 2025.” The company plans to assess the competitive treatment landscape, resource allocation, and potential partnering opportunities before making decisions about future development.