MacroGenics is axing the development of one of its antibody-drug conjugates (ADC) after it flopped in a Phase II study in prostate cancer.
The Rockville, Maryland-based biotech said trials of vobramitamab duocarmazine (vobra duo) would be culled after the safety and efficacy data from the TAMARACK Phase II study (NCT05551117) did not support additional financial investment.
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Based on a 21 February cut-off, the study reported a radiographic progression-free survival (rPFS) of 9.5 months for the 2.0mg/kg cohort and of 10 months for the 2.7mg/kg cohort in patients with metastatic castration-resistant prostate cancer (mCRPC).
Following the announcement, the Nasdaq-listed company’s stock price dropped by 10% from a 20 March close of $2.10 to a 21 March low of $1.89 (correct as of 12pm ET).
President of MacroGenics, Dr. Scott Koenig said: “The results of the TAMARACK Phase II study of vobra duo in mCRPC do not support additional financial investment by MacroGenics. We believe the B7-H3 target continues to have potential and are pleased with the progress being made with our alternate anti-B7-H3 ADC, MGC026.”
Investment into vobra duo in other oncology indications had already been paused by the biotech back in November while it awaited a readout from the TAMARACK study. MacroGenics has now said it will seek potential alternatives for partnering on the programme.
Vobra duo is an ADC comprised of a humanised B7-H3 monoclonal antibody (mAb). It is conjugated by a cleavable peptide linker designed to deliver a DNA-alkylating duocarmycin payload to solid tumours that express B7-H3.
The TAMARACK study enrolled 192 patients with mCRPC who had previously received one prior androgen receptor axis-targeted therapy (ARAT). Patients were randomised to receive either 2.0mg/kg or 2.7mg/kg doses of the ADC and were dosed intravenously every four weeks.
Other candidates in MacroGenics’ pipeline
MGC026 is a TOP1i-based ADC that also targets B7-H3. B7-H3 is an antigen with broad expression across multiple solid tumours and a member of the B7 family of molecules involved in immune regulation. MacroGenics said that MGC026 shares the same variable domain as vobra duo.
MGC026 is currently in a Phase I dose escalation study (NCT06242470) in patients with advanced solid tumours, with dose expansion in selected indications expected to initiate in 2025.
MacroGenics is also investigating different mechanisms of action for mCRPC. The company is running a Phase II trial (NCT05848011) of lorigerlimab, a bispecific, tetravalent PD-1 × CTLA-4 DART, in combination with docetaxel.
According to GlobalData analysis, diagnosed prevalent cases of prostate cancer across eight major markets (8MM: The US, France, Germany, Italy, Spain, the UK, Japan, and China) are set to grow by 3.1% from around 3.23 million in 2023 to 4.24 million in 2033. This increase is in part due to the increased survival rate of prostate cancer patients due to modern medicine, combined with underlying demographic changes in the respective markets.
GlobalData is the parent company of Clinical Trials Arena.
