Date: 2014-09-30
Type of information: Publication of results in a medical journal
phase:
Announcement: publication of results in the Journal of Clinical Oncology (JCO)
Company: Celldex Therapeutics (USA - NJ)
Product: glembatumumab vedotin
Action mechanism:
Disease: metastatic melanoma
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On September 30, 2014, Celldex Therapeutics announced the publication of a paper highlighting early studies of glembatumumab vedotin in metastatic melanoma in the Journal of Clinical Oncology (JCO). The paper "A Phase 1/2 Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients with Advanced Melanoma" has been published as Early Release Articles on JCO's website and will appear in a future print edition. The article "A Phase 1/2 Study of the Antibody-Drug Conjugate Glembatumumab Vedotin in Patients with Advanced Melanoma," presents results from the first study of glembatumumab vedotin. The study initially evaluated dosing of glembatumumab vedotin on a once every 3 week (q3w) schedule. For this schedule, a Phase 1 dose escalation was followed by an open-label, single-arm, Phase 2 expansion cohort to further explore the safety and activity of the maximum tolerated dose (MTD). In addition, the study included parallel dose-escalation evaluation of alternate dosing regimens, with glembatumumab vedotin given on days 1 and 8 of a 21-day cycle (q2/3w) or weekly (qw). The primary objectives of this study were to evaluate the safety and pharmacokinetics of glembatumumab vedotin. The primary efficacy endpoint was the objective response rate (ORR) for the q3w expansion cohort. One hundred seventeen patients were treated using the q3w (n=79), q2/3w (n=15) or qw (n=23) schedules. The MTDs were 1.88, 1.5, and 1.0 mg/kg for the q3w, q2/3w and qw schedules, respectively. The most significant treatment-related toxicities were rash, fatigue, alopecia, neuropathy, and neutropenia. Three deaths were reported as potentially treatment related (resulting from pneumococcal sepsis, toxic epidermal necrolysis and renal failure) at doses exceeding the MTDs. In the q3w Phase 2 expansion cohort (n=34), five patients (15%) had a partial response (PR) and eight patients (24%) had stable disease for greater than or equal to 6 months. The overall response rate (ORR) was 2 of 6 (33%) for the q2/3w schedule MTD and 3 of 12 (25%) for the qw schedule MTD. Rash was correlated with a greater ORR and improved progression-free survival. In those patients whose gpNMB expression levels were measured, a trend toward prolonged PFS was seen for patients with tumors expressing higher levels of gpNMB. Subsequent Development in Metastatic Melanoma:
The relationship between efficacy and tumor gpNMB expression will be prospectively explored in future trials using a revised, validated assay. A Phase 2 study is planned in patients with metastatic melanoma.
