Lower dose of vobramitamab duocarmazine in mCRPC improves tolerability

Initial data from the phase 2 TAMARACK study (NCT05551117) suggest that reduced dosing of vobramitamab duocarmazine (vobra duo, previously MGC018) improves the safety and tolerability of the therapy in patients with metastatic castration-resistant prostate cancer (mCRPC), according to a news release from MacroGenics, the developer of the treatment.¹

Based on the interim data, the Independent Data Monitoring Committee has recommended that the study continue as planned without modification.

Data from the study were submitted for presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, but were not accepted.

“While the TAMARACK data will not be presented at the ASCO 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, MD, PhD, president and CEO of MacroGenics, in the news release.¹ “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 end point—in the fall of 2024.”

In a phase 1 study (NCT03729596) of vobra duo administered at 3.0 mg/kg once every 3 weeks, investigators noted preliminary anti-tumor activity in mCRPC, although adverse events led to high rates of dose modifications and early treatment discontinuation. In the current phase 2 study, patients received vobra duo at the lowered dose levels of 2.0 mg/kg and 2.7 mg/kg via intravenous administration once every 4 weeks.

Overall, interim safety data showed that 93.4% of patients (n = 85) who received vobra duo at 2.0 mg/kg (n = 91) and 95.3% of patients (n = 82) who received vobra duo at 2.7 mg/kg (n=86) experienced any treatment-emergent adverse events (TEAEs). The most common TEAEs 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%).

Further, TEAEs of grade 3 or higher occurred in 25.3% of patients (n = 23) who received vobra duo at 2.0 mg/kg and 31.4% of patients (n = 27) who received vobra duo at 2.7 mg/kg.

Among the patients who were on treatment for 12 weeks or less (n = 95), treatment interruptions due to TEAEs occurred in 12.6% of patients (n = 12), and discontinuations due to TEAEs occurred in 5.3% patients (n = 5). Comparatively, in the phase 1 study of vobra duo at 3.0 mg/kg once every 3 weeks, TEAEs led to treatment interruptions in 58.5% of patients and discontinuation of treatment in 14.6% of patients at 12 weeks.

No treatment-related mortality occurred in either cohort of the phase 2 study.

In total, the phase 2 TAMARACK study enrolled 182 patients with mCRPC, of which 177 received treatment with vobra duo. The median age of patients was 70.5 (range, 46-89). All patients had an ECOG performance status of 2 or lower. Among all participants, 16.5% (n = 30) had visceral disease at baseline, 59.9% (n = 109) had RECIST-evaluable disease, and 53.8% (n = 98) had received prior treatment with docetaxel.

At the time of data cutoff (January 4, 2024), patients on the study had received a median of 3 (range, 1-7) cycles of vobra duo. Treatment remains ongoing in 156 patients (85.7%).

The primary end point for the study is rPFS. Secondary outcome measures include objective response rate, duration of response, prostate-specific antigen (PSA) response rate, and time to PSA progression.²

Based on the interim data, the Independent Data Monitoring Committee has recommended that the study continue as planned without modification. According to the news release, MacroGenics plans to provide updated data on the safety and preliminary efficacy of vobra duo by May 31, 2024, and additional clinical data in the fall of 2024.

References

1. MacroGenics provides phase 2 TAMARACK study early interim safety data and plans for future disclosures. News release. MacroGenics, Inc. April 3, 2024. Accessed April 4, 2024. https://www.globenewswire.com/news-release/2024/04/03/2857385/0/en/MacroGenics-Provides-Phase-2-TAMARACK-Study-Early-Interim-Safety-Data-and-Plans-for-Future-Disclosures.html

2. A study of two dose levels of vobramitamab duocarmazine in participants with metastatic castration resistant prostate cancer (Tamarack). ClinicalTrials.gov. Last updated November 13, 2023. Accessed April 4, 2024. https://clinicaltrials.gov/study/NCT05551117