Vobramitamab duocarmazine continues to show promise in mCRPC

Updated data from the phase 2 TAMARCK study (NCT05551117) continue to show safety and preliminary efficacy of the antibody-drug conjugate (ADC) vobramitamab duocarmazine (vobra duo, previously MGC018) in patients with metastatic castration-resistant prostate cancer (mCRPC), according to a news release from MacroGenics, the developer of the therapy.¹

The primary end point for the study is radiographic progression-free survival.

“The interim safety and anti-tumor activity observed to date in the TAMARACK study look very promising for patients with metastatic castration-resistant prostate cancer,” said Johann de Bono, MD, MSc, PhD, FRCP, FMedSci, the Regius Professor of Cancer Research and Professor in Experimental Cancer Medicine at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust, in the news release.¹ “With the limited treatment options currently available to these patients, this novel ADC molecule could potentially become the first therapy targeting B7-H3 in patients with prostate cancer and would represent an important new treatment for this population.”

Initial data from the study were reported in April 2024, showing that reduced dosing of vobra duo (to 2.0 mg/kg and 2.7 mg/kg) improved the safety and tolerability of the treatment in patients with mCRPC. Data cutoff for the initial report was January 4, 2024. MacroGenics has now provided updated safety and efficacy based on a data cutoff of April 12, 2024.²

Data from this analysis show that among prostate-specific antigen (PSA)-evaluable patients (n = 82 for 2.0 mg/kg cohort; n = 71 for 2.7 mg/kg cohort), a confirmed PSA reduction of at least 50% was observed in 43.9% of patients who received vobra duo at 2.0 mg/kg and 36.6% of patients who received vobra duo at 2.7 mg/kg.

Further, the disease control rate (consisting of complete responses, partial responses, and stable disease) was 91.1% in the 2.0 mg/kg cohort and 87.5% in the 2.7 mg/kg cohort. The overall response rate (consisting of confirmed complete and partial responses) was 17.8% in the 2.0 mg/kg arm and 25.0% in the 2.7 mg/kg arm. The overall response rate (consisting of complete and partial responses, including those unconfirmed) was 24.4% among those who received vobra duo at 2.0 mg/kg and 43.8% among those who received vobra duo at 2.7 mg/kg.

Regarding safety, treatment-emergent adverse events (TEAEs) of all grades occurred in 98.9% and 100% of patients in the 2.0 mg/kg and 2.7 mg/kg arms, respectively. Grade 3 or higher TEAEs occurred in 54.4% of patients in the 2.0 mg/kg arm and 51.2% of patients in the 2.7 mg/kg arm.

In total, 11.1% of patients in the 2.0 mg/kg arm and 15.1% of patients in the 2.7 mg/kg arm discontinued treatment due to a TEAE. Additionally, in the 2.0 mg/kg arm, 43.3% of patients underwent a dose reduction due to a TEAE and 42.2% underwent a dose interruption. In the 2.7 mg/kg cohort, dose reductions and dose interruptions occurred in 51.2% and 55.8% of patients, respectively.

In total, 91 patients were enrolled in the 2.0 mg/kg cohort and 90 patients were enrolled in the 2.7 mg/kg cohort. All patients received vobra duo via intravenous administration once every 4 weeks. The median number of treatment cycles was 5 (range, 1-10).

Patients were eligible for the trial if they had mCRPC, had received one prior ARAT, had received up to 1 prior docetaxel-containing regimen, and had received 3 or fewer prior lines of therapy for mCRPC.

The primary end point for the study is radiographic progression-free survival. Secondary outcome measures include AEs, objective response rate, duration of response, PSA response rate, and time to PSA progression.³

Vobra duo is an ADC that target B7-H3, an antigen expressing across multiple solid tumor types. According to the news release,¹ MacroGenics plans to expand the TAMARACK study to other patient populations, including those with non-small cell lung cancer, small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, and anal cancer. Dosing for these cohorts is expected to begin in mid-2024.

Further, the company announced that they are preparing for the potential initiation of a phase 3 study of vobra duo in patients with mCRPC in 2025. The initiation of the phase 3 study will be dependent on final safety, efficacy, and durability data from the TAMARACK study, including findings on the primary end point of rPFS, which are expected to be shared in the second half of 2024.

The company is also currently enrolled patients in a phase 1/2 dose escalation study (NCT05293496) of vobra duo in combination with lorigerlimab in patients with advanced solid tumors, including mCRPC renal cell carcinoma, melanoma, pancreatic cancer, hepatocellular carcinoma, and ovarian cancer.⁴ MacroGenics plans to initiate a dose expansion study of this combination in mCRPC and at least 1 other indication in 2024.

References

1. MacroGenics provides update on corporate progress, first quarter 2024 financial results and interim TAMARACK phase 2 study data. News release. MacroGenics. May 9, 2024. Accessed May 10, 2024. http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-provides-update-corporate-progress-first-quarter

2. MacroGenics: TAMARACK phase 2 data. MacroGenics. May 9, 2024. Accessed May 10, 2024. https://www.globenewswire.com/Tracker?data=bWBEgz4w6cMmYLvpNdSIqaMEhKprW3ogldQiAKqRViMqIgIXnzhDSzCWi87TYegguKWMx3ckYzScrd8_Z3clSxtLcGha5VC9IeHMnO2NxR0B6KytPYCx5gYLF5hyfwgtmhGEyTZynBPXGFvfrsSLXg==

3. 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 May 10, 2024. https://clinicaltrials.gov/study/NCT05551117

4. A study of MGC018 in combination with MGD019 in participants with advanced solid tumors. ClinicalTrials.gov. Last updated March 15, 2024. Accessed May 10, 2024. https://clinicaltrials.gov/study/NCT05293496