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

October 3, 2022 updated by: Ludwig Institute for Cancer Research

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

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]).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago Hospital
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Cancer Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age ≥ 18 years of age.
  2. Histologically proven metastatic cutaneous, mucosal, or unknown primary melanoma.
  3. Measurable disease using Response Evaluation Criteria in Solid Tumors (RECIST).
  4. Ambulatory (Eastern Cooperative Oncology Group [ECOG] performance status 0 or 1) or expected survival ≥ 4 months.

  5. 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
  6. Able and willing to give valid written informed consent.

Exclusion Criteria:

  1. 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.
  2. Mental impairment that may have compromised the ability to give informed consent and comply with the study requirements.
  3. Participation in any other clinical trial involving chemotherapy, radiotherapy, or other immunotherapy within 4 weeks prior to study enrollment.
  4. Prior exposure to anti-GD3 antibodies.
  5. Pregnancy or breastfeeding.
  6. Women of childbearing potential who refused or were unable to use effective means of contraception.
  7. 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.
  8. 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).
  9. Autoimmune-related hypothyroidism and vitiligo-like depigmentation were allowed provided the patient was medically stable with treatment (thyroid-hormone replacement or observation).
  10. 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.
  11. 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Cohort 1

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
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
Other Names:
  • Intron A
  • Interferon-α2b
Drug: KW2871
5 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
10 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
20 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
EXPERIMENTAL: Cohort 2

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
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
Other Names:
  • Intron A
  • Interferon-α2b
Drug: KW2871
5 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
10 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
20 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
EXPERIMENTAL: Cohort 3

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
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
Other Names:
  • Intron A
  • Interferon-α2b
Drug: KW2871
5 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
10 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab
Drug: KW2871
20 mg/m^2 IV every 2 weeks until disease progression
Other Names:
  • Ecromeximab

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Median Progression-free Survival (PFS) With 95% Confidence Intervals
Time Frame: From baseline through up to 17 months post-baseline
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)
Time Frame: From baseline through up to 17 months post-baseline
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of Patients With Best Overall Tumor Response
Time Frame: From baseline through up to 17 months post-baseline
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.
From baseline through up to 17 months post-baseline
Number of Patients With Human Antichimeric Antibody (HACA) Reactivity To KW2871
Time Frame: From baseline through up to 17 months post-baseline
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.
From baseline through up to 17 months post-baseline
Maximum KW2871 Antibody Levels in Plasma Following the First Infusion
Time Frame: At Baseline and Study Day 3
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.
At Baseline and Study Day 3

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ludwig Institute for Cancer Research

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Chicago
University of Pittsburgh
Life Science Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 28, 2008

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 3, 2014

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 3, 2014

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 14, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2008

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 16, 2008

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 12, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 3, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • LUD2007-001
  • UPCI07-023
  • UCH15689B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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