Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Gaucher Disease Type 3

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Anti-Infective Agents

Antineoplastic Agents

Antibodies

Immunoglobulins

Interferons

Interferon-alpha

Ecromeximab

Antiviral Agents

Antineoplastic Agents, Immunological

KW2871: 5 mg/m\^2 IV every 2 weeks until disease progression

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

KW2871: 10 mg/m\^2 IV every 2 weeks until disease progression

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

KW2871: 20 mg/m\^2 IV every 2 weeks until disease progression

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

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

5 mg/m\^2 IV every 2 weeks until disease progression

KW2871

10 mg/m\^2 IV every 2 weeks until disease progression

20 mg/m\^2 IV every 2 weeks until disease progression

John M. Kirkwood, MD

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 \[PBMCs\]).

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.

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

PFS was calculated from the date of the first infusion to the date of documented progression or death, whichever occurred first. PFS analyses were performed using Kaplan-Meier methods for all patients combined and for patients in Cohort 3. Based on published results from Phase 3 randomized clinical trials in patients with metastatic melanoma at the time of study initiation, 2.5 months was estimated as a conservative (i.e., somewhat high) external standard of median PFS. The intent of this study was to improve this standard by ≥ 70% to a median PFS of ≥ 4.3 months for patients treated with KW2871 combined with HDI. If the therapeutic target of 4.3 months for median PFS represented the true underlying treatment effect of KW2871 plus HDI, then 23 patients would provide 80% power to detect a statistically significant improvement (α = 0.05; 1-sided test) over the 2.5-month external standard.

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life-threatening), or Grade 5 (fatal). TEAEs were reported based on clinical laboratory tests, physical examinations, and vital signs from pre-treatment through the study period. Causal relationship of each TEAE to study treatment was evaluated by the investigator separately for HDI and KW2871. Regimen-limiting toxicity was defined as an HDI-related dose-limiting toxicity (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.

Tumor responses were evaluated using whole body computed tomography and categorized according to the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0) at Screening, on Days 29, 57, 85, 115, 143, 171, 227, 283, 339, and at the End of Study Visit. Patients who were treated beyond 49 weeks were to undergo clinical and radiologic assessments per the standard of care. Per RECIST, target lesions are categorized as follows: Complete Response (CR): Disappearance of all target lesions \[no evidence of disease\]; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria.

Blood samples were collected for the analysis of HACA at baseline, on Days 29, 115, 143, 171, 199, 227, 255, 283, 311, 339, and at the End of Study visit. Measurement of HACA development in plasma was performed with a BIAcore 2000 biosensor (Biacore AB, Uppsala, Sweden), using the BDF TM015 method. HACA positivity was defined as an increase in binding evident in the test channel but not in the control channel, with positivity assigned for values exceeding a uniform test threshold.

Blood samples for pharmacokinetic (PK) measurements were collected at baseline and before and 30 minutes after the initial KW2871 infusion on Day 3. The KW2871 antibody protein in patient serum was measured using an enzyme-linked immunosorbent assay (ELISA). The lower limit of quantitation was determined to be 100 ng/mL.

University of Pittsburgh

University of Chicago

Life Science Pharmaceuticals

Ludwig Institute for Cancer Research

AE documentation included onset/resolution dates, severity using the NCI CTCAE (version 3.0), seriousness, study drug action taken, treatment, and outcome. Relationship to study drug was evaluated for both KW2871 and HDI. Treatment-related AEs included those with a "possible", "probable", or "definite" relationship to study drug; preferred terms were counted only once per patient at the maximum reported grade.

KW2871: 5 mg/m\^2 IV every 2 weeks

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week

Cohort 1

KW2871: 10 mg/m\^2 IV every 2 weeks

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week

Cohort 2

KW2871: 20 mg/m\^2 IV every 2 weeks

HDI: 20 MU/m\^2 IV QD for 5 days/week for 4 weeks, then 10 MU/m\^2 SC 3 days/week

Cohort 3

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Body Mass Index

Safety Analysis Set (includes all patients who received at least 1 dose of KW2871 and initial treatment with HDI)

Jonathan Skipper PhD

All evaluable patients in Cohorts 1, 2, and 3 combined

Patients who received initial treatment with HDI and at least 1 infusion of KW2871 and experienced a PFS event (progression or death).

Median Progression-free Survival (PFS) With 95% Confidence Intervals

Any TEAE

Maximum TEAE Severity Grade 1/2

Maximum TEAE Severity Grade 3

Maximum TEAE Severity Grade 4

Maximum TEAE Severity Grade 5

Any HDI-related TEAE

Any KW2871-related TEAE

Any SAE

Any TEAE leading to withdrawal of HDI+KW2871

Any TEAE leading to withdrawal of HDI only

Any TEAE leading to withdrawal of KW2871 only

Regimen-limiting toxicity

Patients who received initial treatment with HDI and at least 1 infusion of KW2871.

Number of Patients With Treatment-emergent Adverse Events (TEAEs)

Number of Patients With Best Overall Tumor Response

Patients who received initial treatment with HDI and at least 1 infusion of KW2871 and had at least 1 post-baseline plasma sample evaluated for HACA.

Number of Patients With Human Antichimeric Antibody (HACA) Reactivity To KW2871

Patients who received initial treatment with HDI and at least 1 infusion of KW2871 and had at least 1 plasma sample evaluated for KW2871 antibody levels.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase II Study of KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma	NCT00679289	Metastatic Mela... Cutaneous Melan...	HDI KW2871 KW2871 KW2871	18 Years -	Ludwig Institute for Cancer Research
Phase II Study of KW2871 Combined With High Dose Interferon-α2b in Patients With Metastatic Melanoma	NCT00679289	Metastatic Mela... Cutaneous Melan...	HDI KW2871 KW2871 KW2871	18 Years -	Ludwig Institute for Cancer Research

Spots Global Cancer Trial Database for hdi

Every month we try and update this database with for hdi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hdi

Every month we try and update this database with for hdi cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hdi cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.