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

NCT00679289 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: LUD2007-001UPCI07-023UCH15689B
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief 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 \[PBMCs\]).

Conditions

Metastatic Melanoma; Cutaneous Melanoma

Keywords

KW2871; Ecromeximab; Anti-ganglioside; Antibody; Interferon alpha; Metastatic melanoma

Outcome Measures

Primary Outcomes (2)

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

  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.

  From baseline through up to 17 months post-baseline

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

  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.

  From baseline through up to 17 months post-baseline

Secondary Outcomes (3)

• Number of Patients With Best Overall Tumor Response

  From baseline through up to 17 months post-baseline

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

  From baseline through up to 17 months post-baseline

• Maximum KW2871 Antibody Levels in Plasma Following the First Infusion

  At Baseline and Study Day 3

Study Arms (3)

Cohort 1

EXPERIMENTAL

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

Drug: HDI; Drug: KW2871

Cohort 2

EXPERIMENTAL

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

Drug: HDI; Drug: KW2871

Cohort 3

EXPERIMENTAL

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

Drug: HDI; Drug: KW2871

Interventions

HDI DRUG

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

Also known as: Interferon-α2b, Intron A

Cohort 1; Cohort 2; Cohort 3

KW2871 DRUG

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

Also known as: Ecromeximab

Cohort 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years of age.
• Histologically proven metastatic cutaneous, mucosal, or unknown primary melanoma.
• Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST).
• Ambulatory (Eastern Cooperative Oncology Group \[ECOG\] performance status 0 or 1) or expected survival ≥ 4 months.
• Within the last 2 weeks prior to study day 1, the following laboratory parameters within the ranges specified:
• Hemoglobin: ≥ 9 g/dL
• Platelets: ≥ 100 x 10\^9/L
• Neutrophils: ≥ 1.5 x 10\^9/L
• International normalized ratio: ≤ 2.0 (≤ 3.0 if on warfarin therapy)
• Serum creatinine: ≤ 1.5 x upper limit of normal (ULN)
• Serum total bilirubin: ≤ 1.5 x ULN
• Aspartate aminotransferase/alanine aminotransferase: ≤ 2.5 x ULN
• Able and willing to give valid written informed consent.

You may not qualify if:

• Other malignancy within 3 years prior to study entry for which the patient received active treatment, except for treated melanoma or non-melanoma skin cancer, cervical cancer, and breast carcinoma in situ.
• Mental impairment that may have compromised the ability to give informed consent and comply with the study requirements.
• Participation in any other clinical trial involving chemotherapy, radiotherapy, or other immunotherapy within 4 weeks prior to study enrollment.
• Prior exposure to anti-GD3 antibodies.
• Pregnancy or breastfeeding.
• Women of childbearing potential who refused or were unable to use effective means of contraception.
• Active autoimmune or other disorders that required systemic treatment with immunomodulatory or immunosuppressant medications (i.e., corticosteroids, cyclophosphamide, methotrexate, other biologics). Corticosteroids at substitution doses were allowed.
• Metastatic brain disease was allowed provided that appropriate treatment had been administered (surgery or irradiation) and 2-month follow-up by brain magnetic resonance imaging (MRI) showed disease control (stability or regression).
• Autoimmune-related hypothyroidism and vitiligo-like depigmentation were allowed provided the patient was medically stable with treatment (thyroid-hormone replacement or observation).
• Serious medical illness, such as cardiovascular disease (uncontrolled congestive heart failure or hypertension, active ischemic disease of the heart \[angina\], recent \[\<3 months\] myocardial infarction, severe cardiac arrhythmia), bleeding disorders, obstructive or restrictive pulmonary diseases, active systemic infections requiring antibiotics, serious intercurrent illness requiring hospitalization, inflammatory bowel disorders, or significant psychiatric disease, which in the opinion of the principal investigator would have prevented adequate informed consent or rendered study treatment unsafe or contraindicated.
• Patients with clinical suspicion of human immunodeficiency virus (HIV) or hepatitis underwent the following viral tests: patients with HIV must have had negative antibodies; patients with hepatitis B virus must have had negative antigens; patients with hepatitis C virus must have had a negative test for serum antibodies. If any of the tests were positive, patients were excluded from the study.

Sponsors & Collaborators

• Ludwig Institute for Cancer Research: lead
• University of Pittsburgh: collaborator
• University of Chicago: collaborator
• Life Science Pharmaceuticals: collaborator

Study Sites (2)

University of Chicago Hospital

Chicago, Illinois, 60637, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Tarhini AA, Moschos SJ, Lin Y, Lin HM, Sander C, Yin Y, Venhaus R, Gajewski TF, Kirkwood JM. Safety and efficacy of the antiganglioside GD3 antibody ecromeximab (KW2871) combined with high-dose interferon-alpha2b in patients with metastatic melanoma. Melanoma Res. 2017 Aug;27(4):342-350. doi: 10.1097/CMR.0000000000000353.

  PMID: 28489678 RESULT

Related Links

• Abstract with option to purchase full text

MeSH Terms

Conditions

Melanoma

Interventions

Introns; ecromeximab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes

Results Point of Contact

• Title: Jonathan Skipper PhD
• Organization: Ludwig Institute for Cancer Research

jskipper@lcr.org

12124501539

Study Officials

• John M. Kirkwood, MD

  University of Pittsburgh

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Dose-escalation cohorts

Study Record Dates

• First Submitted: May 14, 2008
• First Posted: May 16, 2008
• Study Start: March 28, 2008
• Primary Completion: February 3, 2014
• Study Completion: February 3, 2014
• Last Updated: October 12, 2022
• Results First Posted: February 9, 2018

Record last verified: 2022-10

Locations

US (2)