Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Antitumor Activity of KN046 in Subjects With Advanced Solid Tumors

May 20, 2018 updated by: Alphamab (Australia) Co Pty Ltd.

An Open-Label, Multi-center, Dose-Escalation Phase I Study to Evaluate Safety, Tolerability, Pharmacokinetics and Immunogenicity of KN046 in Subjects With Advanced Solid Tumors

This is an open-label, multicenter, dose-escalation phase I study to assess the safety, tolerability and preliminary efficacy of KN046 in participants with all advanced solid tumors who are not able to have current standard anti-tumor therapies. The purpose of this study is to determine the maximum tolerated dose (MTD) or a biological effective dose (BED), to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN046 as a single agent in adult participants with advanced solid tumors

Study Overview

Status

Status

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

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.

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 (Anticipated)

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.
21

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 1

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Queensland
      • Southport, Queensland, Australia, 4125
        • Recruiting
        • ICON Cancer Care
        • Contact:
        • Principal Investigator:
          • Craig Underhill

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. The subject must sign the informed consent form prior to the conduct of any study related procedures that are required during the screening period and are not considered part of standard of care.
  2. Subjects must have histologic or cytologic confirmed Advanced solid tumors.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  4. Adequate organ function within 3 weeks prior to initial treatment.
  5. Ability to comply with treatment, procedures and PK sample collection and the required study follow-up procedures.
  6. Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed.
  7. Female patients must have a negative serum or urine pregnancy test
  8. Female patients must not be breastfeeding.

Exclusion Criteria:

  1. Subjects with brain metastases or leptomeningeal are excluded.
  2. Concurrent enrollment in another clinical study, unless in a follow-up period or the study is an observational or non-interventional study.
  3. Any kind of immunotherapy within 6 weeks of the first dose of study treatment.
  4. Prior systemic cytotoxic chemotherapy, other anticancer drugs or growth factor within 28 days of the first dose of study treatment, or any investigational agents within 5 half-lives of the product.
  5. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the 1st dose of study treatment, or have an anticipated need for major surgery during the study.
  6. Palliative radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the 1st dose of study treatment.
  7. Prior treatment or with sequential monotherapy with anti-CTLA-4 and anti-PD-1/PD-L agents.
  8. Patients who have received monotherapy with PD-L1 / PD-1, CTLA4 or other antibodies and had intolerable toxicity or required steroids to manage toxicity.
  9. History of autoimmune or inflammatory disorders.
  10. A current or prior use of immunosuppressive medication within 14 days of the 1st dose of study treatment.
  11. Suspected latent tuberculosis infection, confirmed by Mantoux test and a chest x-ray.
  12. Any unresolved toxicity NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria
  13. Any factors that increase the risk of QT (ECG interval measured from the onset of the QRS complex to the end of the T wave) interval corrected for heart rate (QTc) prolongation or risk of arrhythmic events (e.g., heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age) or mean QTc>470 msec.
  14. Positive blood screen for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV Ab), or human immunodeficiency virus 1/2 antibody (HIV 1/2 Ab).
  15. History of severe allergic reactions to any unknown allergens or to parenteral administered recombinant protein product.

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
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

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: KN046
Drug: KN046
The modified phase I "3 + 3" study design was used in dose escalation from low dose to high dose to determine the MTD.Sequential assignment of Patient cohorts to one of five dose levels of KN046: 0.3 mg/kg,1 mg/kg,3 mg/kg,5 mg/kg,10 mg/kg.

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
Number of participants with dose limiting toxicity (DLT)
Time Frame: During the first cycle (4 weeks) of treatment.
An DLT is defined as a ≥Grade 3 drug-related adverse event occurring within the first cycle (28 days) of dosing (excluding tumor flare causing local pain at sites of known or suspected tumor, localized rash, or a transient ≤Grade 3 infusion reaction) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE).
During the first cycle (4 weeks) of treatment.

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 participants with adverse events (AEs)
Time Frame: From the time of informed consent signed through 90 days after the last dose of KN046，up to 2 years.
An AE is defined as any untoward medical occurrence in a participant administered KN046 and/or pharmaceutical product(s) temporally associated with the use of study treatment, whether or not considered related to the study treatment.
From the time of informed consent signed through 90 days after the last dose of KN046，up to 2 years.
Objective response rate (ORR)
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Duration of response (DoR)
Time Frame: up to 2 years.
Duration of response is defined as the duration from the first documentation of objective response to the first documented disease progression or death due to any cause, whichever occurs first.
up to 2 years.
Progression-free survival (PFS)
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Progression-free survival is defined as the time from the start of treatment with KN046 until the first documentation of disease progression or death due to any cause, whichever occurs first.
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Clinical benefit rate (CBR)
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Clinical benefit rate is defined as the percentage of patients who have achieved complete response (CR), partial response (PR) and stable disease (SD) to KN046 intervention.
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Area under the curve (AUC) of KN046
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Maximum observed concentration (Cmax) of KN046
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Minimum observed plasma concentration (Ctrough) of KN046 at steady state
Time Frame: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Number of subjects who develop detectable anti-drug antibodies (ADAs)
Time Frame: Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.
The immunogenicity of KN046 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.
Number of subjects who develop detectable neutralizing ADA (NADA)
Time Frame: Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.
The neutralizing ADA will be assessed by summarizing the number of subjects who develop detectable neutralizing ADA .
Assessed before KN046 infusion in Cycle 1, 2, 3, 4, 5, 6 and at the mandatory Safety Follow-up Visit, maxium up to 2 years.

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.
Alphamab (Australia) Co Pty Ltd.

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 (Anticipated)

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.
May 21, 2018

Primary Completion (Anticipated)

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.
October 30, 2019

Study Completion (Anticipated)

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.
March 30, 2020

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 8, 2018

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 17, 2018

First Posted (Actual)

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 18, 2018

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.
May 22, 2018

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.
May 20, 2018

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.
May 1, 2018

More Information

Terms related to this study

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.
  • KN046-AUS-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings