Quantum Leap Healthcare Collaborative

Agent Information

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I-SPY Trial Manuscript
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[vic-]trastuzumab duocarmazine

Trade Name:
Agent Chaperone(s):
Treatment Protocol:
SYD985 will be administered via intravenous infusion at 1.2mg/kg q3w x 4, with paclitaxel administered at 80 mg/m2 q1w x 12. This regimen is followed by AC (q2w or q3w) for 4 weeks. Only participants with HER2-positive tumors may be enrolled to this arm.
Date Entered I-SPY:
August 31, 2020
Date Left I-SPY:
No. Participants in Arm:
Graduating Subtypes:
Agent Description:

SYD985 ([vic]-trastuzumab duocarmazine) is an antibody-drug conjugate that binds to HER2. It
consists of the recombinant humanized anti-epidermal growth factor receptor 2 (HER2) monoclonal antibody analog to trastuzumab (SYD977) attached by a cleavable linker (called SYD980), to the duocarmycin prodrug (seco-duocarmycin-hydroxybenzamide-azaindole or seco-DUBA or SYD978). Upon binding to HER2, the linker is  leaved inside the tumor cell by proteases that release the active moiety, duocarmycin, which then binds to the minor groove of DNA, inducing apoptosis; trastuzumab also induces antibody-dependent, cell-mediated cytotoxicity against tumor cells that overexpress HER2.

Preclinical studies indicate SUYD985 is very active in HER2-positive breast cancer models, even those with lower HER2-expression.

Final pCR Probabilities:
Primary Manuscript:
abstractpdfdoi link