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Antibody-drug Conjugates & Bioconjugates


TRPH-222, a SMARTag anti-CD22 ADC, is in a Phase 1 trial for relapsed/refractory B-cell non-Hodgkin’s lymphoma. In a heavily-pretreated population, the drug induced 6 complete responses and 2 partial responses in the first 22 patients dosed (overall response rate, 36.8%).

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PATIENTReporting on 22 heavily pre-treated patients with relapsed/refractory B-cell lymphoma in dose escalation phase. Dose expansion phase will proceed at 7.5 mg/kg.

Two dose limited-toxicities (transient elevation of liver enzymes at 4.2 and 10mg/kg); no DLTs observed at 7.5mg/kg. One other patient discontinued treatment due to grade 3 ocular adverse event (dry eye, blurred vision).

Other adverse events were those commonly associated with ADCs, including neutropenia and thrombocytopenia. These were infrequent and resolved without intervention.

Peripheral neuropathy, a common side-effect observed with maytansine/MMAE conjugates and one that is commonly associated with treatment discontinuation, was infrequent and only observed in patients with prior history of neuropathy.

EFFICACY6 complete responses and 2 partial responses observed in patients with both indolent and aggressive disease (including DLBCL and mantle cell lymphoma).
PHARMACOKINETICSTRPH-222 has high stability in humans; no evidence of released payload in circulation, even at 10 mg/kg dose.