MacroGenics pays for its ASCO exuberance
The company looks rash for promising Tamarack data at the conference, although at least vobra duo’s safety has improved.
The company looks rash for promising Tamarack data at the conference, although at least vobra duo’s safety has improved.
Only last month MacroGenics was promising that phase 2 data with its lead project, vobramitamab duocarmazine, would feature at this year’s ASCO meeting. Yesterday the group was in the embarrassing position of having to admit that its abstract had been rejected.
This unusual scenario would have been avoided if MacroGenics had kept its ASCO hopes to itself. However, a silver lining is that early safety data, released by the company, suggest that reducing vobra duo’s dose has improved its tolerability.
MacroGenics' stock opened up 30% this morning.
It's worth noting that MacroGenics has a track record of testing ASCO's disclosure guidelines: in 2020, a week before the abstracts were released, it gave investors a sneak peek of early data that were later presented at the conference. This included a look at results with vobra duo, then known as MCG018.
The company didn't give a reason for yesterday's ASCO knockback.
Tamarack rollback
The latest results come from Tamarack, a phase 2 trial of the B7-H3-targeting ADC in post-Xtandi/Zytiga metastatic castration-resistant prostate cancer patients.
The study tests vobra duo at 2.0mg/kg and 2.7mg/kg every four weeks. These are doses to which MacroGenics shifted after the phase 1 regimen of 3.0mg/kg every three weeks was linked with high rates of adverse events and discontinuations.
MacroGenics submitted an abstract to ASCO based on interim safety data, and had hoped to present updated safety and preliminary efficacy data at the meeting.
Now the group has had to put out those early safety data itself, and is promising its own update by the end of May. As before, MacroGenics expects to report on radiographic progression-free survival, Tamarack’s primary endpoint, in the second half. The company said during its fourth-quarter earnings call in March that a 40-60% PSA50 response rate, ORR of at least 25% and median rPFS of at least six months would be meaningful.
For now, though, only safety data are available, but they do seem to suggest that the company’s dose-lowering plan has worked, at least in terms of reducing adverse events.
However, MacroGenics has yet to show convincing efficacy with the new vobra duo regimens, and it won’t now be doing that at ASCO. After spooking investors last month by unveiling a new B7-H3 ADC, MGC026, the last thing the company needed was more confusion – but that’s exactly what it’s provided this week.
Adverse events with vobra duo: cross-trial comparison
| Tamarack | Phase 1* | ||
|---|---|---|---|
| 2.0mg/kg Q4W | 2.7mg/kg Q4W | 3.0mg/kg Q3W | |
| N | 91 | 86 | 86 |
| Any TEAE | 93% | 95% | 97% |
| TEAE gr≥3 | 25% | 31% | 56% |
| Serious AE | 12% | 20% | 34% |
| Drug interruption due to AE | 11% | 19% | 48% |
| Drug discontinuation due to AE | 4% | 2% | 8% |
| Fatal AE | 0% | 0% | 2% |
Note: *included mCRPC, NSCLC, TNBC & melanoma patients. Source: company release & ESMO 2021 poster.
At the time of publishing neither MacroGenics nor ASCO had responded to ApexOnco's query asking for the reason for the abstract's rejection. This story has been updated to include MacroGenics' opening share price.
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