MacroGenics said it will no longer dose the remaining patients who could have received more in a Phase 2 trial studying its antibody-drug conjugate in prostate cancer, after a recommendation by an independent data monitoring committee.
Scott Koenig“Patient safety is our top priority, and having reached the study’s primary endpoint, we decided to discontinue additional dosing for the remaining TAMARACK participants who had not yet completed treatment,” MacroGenics CEO Scott Koenig said in a late Tuesday release.
The company’s stock $MGNX dropped nearly 30% on Wednesday.
The study is investigating the ADC named vobramitamab duocarmazine, or vobra duo, in metastatic castration-resistant prostate cancer (mCRPC). Most of the remaining participants in the 382-patient trial that won’t receive any more treatment had already received eight to 12 cycles of the drug every four weeks.
“We expect to have the data necessary to determine next steps for the vobra duo program later this year,” Koenig said, adding that they will present more results at ESMO in Barcelona in September. The poster will include safety, efficacy and radiographic progression-free survival data collected from a July 9 data cutoff, the company said.
In May, MacroGenics said it was investigating three patient deaths, two of whom died due to pneumonitis and another from a pleural effusion.
B Riley Securities analysts wrote in a Tuesday note that stopping TAMARACK “may indicate a cohort of patients benefiting from promising durability” because median dosing cycles have increased since the previous data cutoff in April. But, they said, efficacy “appears to come at the cost of accumulating toxicity, which has been viewed as the critical risk with longer-term [vobra duo] exposure.”
The analysts added that they no longer see a favorable risk-benefit profile for the two vobra duo dose levels tested in the trial, “implying the likely failure of original hypothesis set out for TAMARACK,” which is to pinpoint the best dosing schedule. TAMARACK studied 2.7 mg and 2 mg doses. In an earlier Phase 1/2 study, a 3 mg dose was deemed nonviable due to safety and tolerability concerns.
The analysts’ concerns now “relate to any future regulatory action, e.g., patient safety-related FDA hold, that could serve as an additional negative catalyst.”
In interim TAMARACK data released in May, 25% of patients given the higher 2.7 mg dose had an objective response, compared with 17.8% of patients in the 2 mg group. The median number of cycles of vobra duo administered was five.
Meanwhile, MacroGenics also said on Tuesday that its cash runway has been extended into 2026, due in part to a $100 million milestone payment from Incyte. The milestone payment comes from development progress of Zynyz, an intravenous PD-1 inhibitor approved for metastatic or recurrent locally advanced Merkel cell carcinoma.
Incyte originally licensed it from MacroGenics under a 2017 exclusive global collaboration and license agreement, and Incyte is continuing to investigate the drug in other indications. MacroGenics potentially has another $210 million in development and regulatory milestones and up to $330 million in commercial milestones coming from the same deal.