On April 3, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on the Phase 2 TAMARACK study of vobramitamab duocarmazine (vobra duo, previously known as MGC018) in patients with metastatic castration-resistant prostate cancer (mCRPC) (Press release, MacroGenics, APR 3, 2024, View Source [SID1234641742]).

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As previously disclosed, safety data from the Company’s ongoing TAMARACK Phase 2 study was submitted in early February to the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) for presentation at the upcoming Annual Meeting that begins May 31. The abstract containing this early interim data, based on a January 4, 2024 data cut-off, was not accepted. The submitted abstract is provided below.

"While the TAMARACK data will not be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting, we intend to maintain our previously disclosed plan to share further TAMARACK interim data, including updated safety and preliminary efficacy, by the end of May," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer. "This updated information will be based upon a future data cut-off. In addition, we still anticipate presenting updated clinical data – including radiographic progression-free survival, or rPFS, the study’s primary endpoint – in the Fall of 2024."

Abstract as submitted on February 6, 2024:

"Title
Vobramitamab duocarmazine (vobra duo), a B7-H3 directed antibody drug conjugate (ADC) in metastatic castration resistant prostate cancer (mCRPC): Early data from the Phase 2 TAMARACK study.

Background
Vobra duo (MGC018) is an ADC with a duocarmycin-based DNA-alkylating payload. Vobra duo targets B7-H3, which is highly expressed in multiple tumor types including prostate cancer and has limited expression in normal tissue. Phase 1 testing (NCT03729596) of vobra duo at 3.0 mg/kg Q3W demonstrated anti-tumor activity in mCRPC, although adverse events resulted in high rates of dose modifications and early treatment discontinuation. Lowering the starting dose may improve tolerability, extend treatment duration, and enhance effectiveness.

Methods
TAMARACK is an ongoing randomized, open-label, Phase 2 dose selection study assessing the efficacy, safety, and tolerability of two dose levels of vobra duo (2.0 mg/kg and 2.7 mg/kg IV Q4W). The study enrolled patients (pts) with mCRPC previously treated with abiraterone, enzalutamide, or apalutamide; prior docetaxel was allowed. The primary endpoint is investigator-assessed PFS at 6 months.

Results
At data cutoff (Jan 4, 2024), 182 pts with mCRPC enrolled on TAMARACK, of which 177 received vobra duo. Enrolled pts were 46 to 89 years of age (median 70.5) with ECOG performance status ≤ 2. Thirty (16.5%) had visceral disease at baseline, 109 (59.9%) had RECIST-evaluable disease, and 98 (53.8%) received prior docetaxel. At this early data cut, pts have received a median of 3 (range 1 to 7) cycles of vobra duo; treatment is ongoing in 156 (85.7%). A summary of treatment-emergent adverse events (TEAEs) is presented below.

Vobra duo
2.0 mg/kg (n=91) Vobra duo
2.7 mg/kg (n=86)
Any TEAE 85 (93.4%) 82 (95.3%)
TEAE Grade ≥ 3 23 (25.3%) 27 (31.4%)
Serious AE 11 (12.1%) 17 (19.8%)
Drug Interruption due to AE 10 (11.0%) 16 (18.6%)
Drug Discontinuation due to AE 4 (4.4%) 2 (2.3%)
Fatal AE 0 0
The most common (≥10%) TEAEs regardless of dose were asthenia (40.7%), nausea (27.7%), fatigue (20.3%), decreased appetite (19.2%), anemia (17.5%), constipation (16.4%), diarrhea (14.7%), headache (13.0%), neutropenia (12.4%), and peripheral edema (10.7%). In the subset (n = 95) of TAMARACK pts on treatment for ≥ 12 weeks or who discontinued study treatment within 12 weeks, TEAEs led to drug interruption in 12 (12.6%) and discontinuation in 5 (5.3%) pts. This compares favorably to the rate of drug interruption (58.5%) and discontinuation (14.6%) observed at 12 weeks in pts with mCRPC who received vobra duo at 3.0 mg/kg Q3W on the Phase 1 study. Following the pre-specified interim analysis for futility on both arms, the IDMC recommended continuing the study as planned without modification.

Conclusions
Preliminary safety data from TAMARACK suggest that reducing the dose and frequency of vobra duo improves its safety and tolerability in men with mCRPC. The authors anticipate sharing preliminary efficacy data and updated safety data at the conference. Clinical trial information: NCT05551117."

MacroGenics would like to thank the abstract authors, including: Johann S. De Bono, Carole Helissey, Karim Fizazi, Eric Voog, Pablo Maroto-Rey, Guilhem Roubaud, Emmanuel S. Antonarakis, Shahneen Sandhu, Neal D. Shore, Raffaele Ratta, Begoña Pérez Valderrama, Christof Vulsteke, Galina Marr, Ashley Ward, Enxu Zhao, Josep M. Piulats, on behalf of the TAMARACK Investigators.