MacroGenics announces updated efficacy, safety data from TAMARACK Phase 2 study

MacroGenics presented updated efficacy and safety results from the TAMARACK Phase 2 study of vobramitamab duocarmazine, an antibody-drug conjugate that targets B7-H3, for patients with metastatic castration-resistant prostate cancer. The data were featured in a poster presentation at the European Society for Medical Oncology Congress, taking place in Barcelona, Spain from September 13-17, 2024. The abstract submitted to ESMO was based on a data cut-off as of April 12, 2024; updated data based on a cut-off date of July 9, 2024. The TAMARACK trial enrolled a total of 181 participants, with 176 participants receiving at least one dose of vobra duo at either 2.0 mg/kg q4W or 2.7 mg/kg q4W. As of the data cut-off date, 23 and 16 participants remained on treatment in the 2.0 mg/kg and 2.7 mg/kg cohorts, respectively. While mCRPC study participants are no longer being dosed in the study, participants continue to be monitored for adverse events, disease progression, and survival. Overall, the company believes that the results to date from the TAMARACK study indicate antitumor activity associated with vobra duo in mCRPC as demonstrated by the protocol-specified primary endpoint of landmark 6-month radiographic progression-free survival rate, as well as other measures of tumor response. In the intent-to-treat population, 6-month rPFS rate was 69% for the 2.0 mg/kg arm and 70% for the 2.7 mg/kg arm. Landmark 6-month rPFS rates were consistent across taxane-naive study participants and taxane pre-treated study participants, regardless of treatment arm. Although immature, with only 65 PFS events as of the data cut-off, median rPFS was approximately 8.5 months for the 2.0 mg/kg cohort and 7.5 months for the 2.7 mg/kg cohort. Because these results were immature as of the cutoff date, they are likely to change as additional events accrue. Out of 45 RECIST-response evaluable patients in the 2.0 mg/kg arm, the confirmed objective response rate was 20.0% and the unconfirmed ORR was 26.7%. Out of 32 RECIST-response evaluable patients in the 2.7 mg/kg arm, the confirmed ORR was 40.6% and the unconfirmed ORR was 46.9%. Confirmed ORR was comparable between taxane-naive study participants and taxane pre-treated study participants, regardless of treatment arm. Tumor responses did not appear to correlate with baseline B7-H3 expression based on archival tissue samples of mixed age. In the 2.0 mg/kg cohort, 65.6% of study participants experienced a Grade greater than or equal to 3 treatment-emergent AE; this cohort had a discontinuation rate of 25.6% and a dose reduction rate of 50.0% due to TEAEs. In the 2.7 mg/kg cohort, 62.8% of study participants experienced a Grade greater than or equal to 3 TEAE; this cohort had a discontinuation rate of 38.4% and a dose reduction rate of 54.7% due to TEAEs. The majority of TEAEs with a greater than or equal to 10% incidence rate in either treatment arm was limited to Grade 1/2 events. Eight fatal treatment-related AEs as assessed by the treating physician: five in the 2.0 mg/kg cohort and three in the 2.7mg/kg cohort. These include three events of pneumonitis, and one event each of cardiac failure, stress cardiomyopathy, ventricular fibrillation, pleural effusion, and gastrointestinal hemorrhage. Rates of treatment-related AEs and treatment-related severe AEs were similar between taxane-naive and taxane pre-treated study participants. In the 2.0 mg/kg cohort, 25.6% of study participants remained on study drug as of July 9, 2024. Study participants received a median number of 6 doses, with a median dose intensity of 92.6%. In the 2.7 mg/kg cohort, 18.6% of study participants remained on study drug as of the data cut-off date. Study participants received a median number of 6 doses, with a median dose intensity of 81.7%. Taxane-naive study participants experienced higher rates of dose reductions due to TEAEs and dose interruptions due to TEAEs compared to taxane pre-treated study participants.