Zymeworks Advances HER2 Bispecific Antibody-Drug Conjugate, ZW49, into Expansion Cohort Stage of Clinical Development
Zymeworks Inc. (NYSE: ZYME), a clinical-stage biopharmaceutical company developing multifunctional biotherapeutics, announced today that the Company has begun enrolling patients into the expansion cohort portion of the ongoing Phase 1 clinical trial for ZW49, its novel HER2-targeted antibody-drug conjugate (ADC). Supporting data from the Phase 1 dose escalation portion were highlighted today via a webcast and conference call and are summarized below.
Phase 1 Dose Escalation Study Design
The dose escalation portion of the study employed a standard 3 + 3 design to evaluate escalating doses within different dosing regimens including once every two week (Q2W) and once every three week (Q3W) schedules with the objective of selecting a dose and schedule to advance into the expansion cohorts.
To date patients from sites across the US and Canada with a variety of heavily pretreated HER2‑positive cancer types have been enrolled, including breast cancer, gastroesophageal adenocarcinoma, gynecologic cancers, non-small cell lung cancer, anal cancer, and colorectal cancer.
ZW49 Safety and Tolerability
In the 35 patients who have received ZW49 across all dosing regimens, there have been no dose limiting toxicities, no treatment-related hematologic toxicities including neutropenia or thrombocytopenia, no treatment-related pulmonary toxicity including interstitial lung disease or pneumonitis, and no treatment-related liver toxicity. There have been no treatment-related deaths.
Over 90% of treatment-related adverse events have been mild or moderate (Grade 1 or 2) in severity, with the most common being keratitis, fatigue, and diarrhea, which have been reversible and manageable in an outpatient setting. There have been no discontinuations due to treatment-related adverse events, and the maximum-tolerated dose has not yet been established.
ZW49 Interim Antitumor Activity
ZW49 has demonstrated antitumor activity across all regimens and dose levels evaluated to date, including at the starting dose of 1 mg/kg Q2W. Partial responses and stable disease per RECIST 1.1 have been observed in both Q2W and Q3W dosing regimens, with the Q3W regimen starting to demonstrate a dose-response relationship. Beginning at the initial dose of 2.0 mg/kg Q3W, several patients experienced stable disease including some with disease control greater than four months. At the highest doses tested in the Q3W of 2.5 or 3.0 mg/kg there were six response-evaluable patients with centrally confirmed HER2‑positive disease spanning several different tumor types. The antitumor activity in these six patients consisted of two patients with confirmed partial responses and two patients with stable disease, three of which are still active on study. This regimen is currently enrolling patients at the 3 mg/kg dose with the potential to add new escalation cohorts.