NCT00679289

Phase II Study of KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma

Phase II Study of the Anti-Ganglioside GD3 Mouse/Human Chimeric Antibody KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Ludwig Institute for Cancer Research · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This was a Phase 2, open-label study of KW2871 (ecromeximab) in combination with high-dose interferon-α2b (HDI) in patients with metastatic melanoma. The primary objectives of this study were to assess progression-free survival (PFS) and safety. The secondary objectives were to assess the objective response rate, KW2871 pharmacokinetics (PK), and other exploratory immunology as indicated (e.g., development of human anti-chimeric antibodies \[HACA\], activity of antibody-dependent cell-mediated cytotoxicity \[ADCC\] and complement-dependent cytotoxicity \[CDC\] in peripheral blood, number and functional state of tumor-infiltrating immune cells and expression of GD3 in immune and tumor cells of tumor biopsies, and markers of interferon \[IFN\] response/resistance and markers of resistance to ADCC/CDC in peripheral blood mononuclear cells \[PBMCs\]).

Detailed description

Eligible patients were sequentially enrolled into dose-escalating cohorts to receive KW2871 intravenously (IV) once every 2 weeks starting on Day 3 of Week 1 at the following doses: 5 mg/m\^2 in Cohort 1, 10 mg/m\^2 in Cohort 2, and 20 mg/m\^2 in Cohort 3. HDI was administered concurrently at a dose of 20 million units (MU)/m\^2 IV once daily (QD) for 5 consecutive days per week for 4 weeks (induction phase), followed by 10 MU/m\^2 administered subcutaneously (SC) 3 times per week (maintenance phase). Patients received KW2871 and HDI combination therapy until disease progression requiring treatment intervention that would have interfered with the interpretation of the study results. Initially, 3 patients were enrolled within a cohort and evaluated for dose-limiting toxicity (DLT) and regimen-limiting toxicity (RLT) for the first 8 weeks of study treatment. If 1 of 3 patients experienced an RLT, the cohort was expanded to 6 patients. Escalation to the next higher dose cohort proceeded if the RLT rate was \<33% (0/3 or 1/6 patients) in a given cohort. The combination treatment was considered safe if ≤ 20% patients experienced RLT. DLT was defined as any adverse event (AE) that required reduction of the HDI dose or discontinuation of KW2871. RLT was defined as an HDI-related DLT that required more than 2 dose reductions of HDI during the induction phase or the first 4 weeks of the maintenance phase, or any KW2871- or regimen-related DLT.

Conditions

• Metastatic Melanoma
• Cutaneous Melanoma

Interventions

Type	Name	Description
DRUG	HDI	20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week until disease progression
DRUG	KW2871	5 mg/m\^2 IV every 2 weeks until disease progression
DRUG	KW2871	10 mg/m\^2 IV every 2 weeks until disease progression
DRUG	KW2871	20 mg/m\^2 IV every 2 weeks until disease progression

Timeline

• Start date: 2008-03-28
• Primary completion: 2014-02-03
• Completion: 2014-02-03
• First posted: 2008-05-16
• Last updated: 2022-10-12
• Results posted: 2018-02-09

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study