MacroGenics cuts down its Tamarack
Vobra-duo is discontinued at long last.
Vobra-duo is discontinued at long last.
After Sutro and Elevation Oncology, MacroGenics on Thursday became the latest biotech to throw in the towel with its lead asset, and switch focus to earlier-stage pipeline projects.
For MacroGenics the decision to terminate vobramitamab duocarmazine has been a long time coming, and follows treatment-related deaths that caused its Tamarack study to be stopped, and the announced departure of its chief executive, Scott Koenig. Despite this the company continued to talk up the prospects of a phase 3 study, but now sense has prevailed, and Tamarack is being buried.
An update to Tamarack, in metastatic castration-resistant prostate cancer, had been awaited since the last cut of the results, at September's ESMO conference, showed landmark six-month radiographic PFS of 69% and 70% for the 2.0mg/kg and 2.7mg/kg vobra-duo doses respectively, and patient deaths rising from five to eight.
Mature rPFS
MacroGenics promised a first-quarter analysis of mature rPFS, and this has now been provided: at a 21 February data cutoff the median numbers for the respective two vobra-duo doses are 9.5 months and 10.0 months.
These are more impressive than immature curves had earlier suggested, and numerically above docetaxel's 8 months or so. As such, this would be a positive result were it not for vobra-duo's toxicity, and while MacroGenics hasn't reported any additional deaths it states that "safety data remained consistent with prior disclosures".
Though MacroGenics insists that it is exploring the possibility of licensing out vobra-duo this seems a long shot given the anti-B7-H3 ADC's profile. It says no further work will be carried out, though it continues to believe in the target, and is advancing its follow-on B7-H3-directed ADC, MGC026, which employs a topoisomerase 1 inhibitor rather than DNA alkylating agent payload.
What remains of MacroGenics’ pipeline
| Project | Mechanism | Note | Competition |
|---|---|---|---|
| Lorigerlimab | PD-1 x CTLA-4 bispecific MAb | Ph2 Lorikeet data in mCRPC delayed from H1 to H2 2025; ph2 Linnet trial in ovarian cancer starts mid-2025 | Marketed combinations of PD-1 and CTLA-4 MAbs; bispecifics from AstraZeneca (volrustomig) & Akeso (cadonilimab) |
| MGC026 | B7-H3 ADC | Ph1 started Mar 2024 | Includes clinical-stage ADCs from Merck/Daiichi (ifinatamab deruxtecan), GSK (GSK5764227) & BioNTech/DualityBio (BNT324/DB-1311) |
| MGC028 | Adam9 ADC | Ph1 starts Mar 2025 | None |
| MGD024 | CD123 T-cell engager | Gilead has opt-in rights during ph1 | Numerous, but anti-CD123 approaches have disappointed |
| MGC030 | Undisclosed ADC | IND filing planned in 2026 | NA |
| Enoblituzumab | B7-H3 MAb | Only remaining work is investigator-sponsored ph2 study | NA |
| Vobramitamab duocarmazine | B7-H3 ADC | Discontinued after ph2 Tamarack trial in mCRPC | NA |
Source: OncologyPipeline.
Perhaps more controversial will be MacroGenics' decision to start the phase 2 Linnet trial of the anti-PD-1 x CTLA-4 bispecific MAb lorigerlimab in ovarian cancer. This will test a 6mg/kg thrice-weekly dose, investigate response rates as primary endpoint, and start by mid-2025.
This mechanism features multiple competitors, with AstraZeneca's volrustomig already in phase 3, for instance, and CTLA-4 blockade in general is associated with notable toxicities. Meanwhile, results from lorigerlimab's prostate cancer trial, Lorikeet, expected in the first half, have now slipped into the second, MacroGenics said.
The group might fare better with MGC028, an anti-Adam9 ADC that has no other active industry competition, according to OncologyPipeline, but this asset is only just starting phase 1. Also newly disclosed is the entry into MacroGenics' pipeline of MGC030, an ADC against an undisclosed target.
The company says it had $202m in the bank at the end of last year, and like at Sutro and Elevation remaining cash is being redirected to the early pipeline. All three companies are now under pressure to show that it wouldn't be better to follow Cargo Therapeutics and seek a way to hand the money back to investors.
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