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

Alphamab (Australia) Co Pty Ltd.1 site in 1 country21 target enrollmentMay 21, 2018

ConditionsAdvanced Solid Tumors

InterventionsKN046

DrugsKN046

Overview

Phase: Phase 1
Intervention: KN046
Conditions: Advanced Solid Tumors
Sponsor: Alphamab (Australia) Co Pty Ltd.
Enrollment: 21
Locations: 1
Primary Endpoint: Number of participants with dose limiting toxicity (DLT)
Last Updated: 7 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

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

Registry

clinicaltrials.gov

Start Date

May 21, 2018

End Date

March 30, 2020

Last Updated

7 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Alphamab (Australia) Co Pty Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.
•Subjects must have histologic or cytologic confirmed Advanced solid tumors.
•Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
•Adequate organ function within 3 weeks prior to initial treatment.
•Ability to comply with treatment, procedures and PK sample collection and the required study follow-up procedures.
•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.
•Female patients must have a negative serum or urine pregnancy test
•Female patients must not be breastfeeding.

Exclusion Criteria

•Subjects with brain metastases or leptomeningeal are excluded.
•Concurrent enrollment in another clinical study, unless in a follow-up period or the study is an observational or non-interventional study.
•Any kind of immunotherapy within 6 weeks of the first dose of study treatment.
•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.
•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.
•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.
•Prior treatment or with sequential monotherapy with anti-CTLA-4 and anti-PD-1/PD-L agents.
•Patients who have received monotherapy with PD-L1 / PD-1, CTLA4 or other antibodies and had intolerable toxicity or required steroids to manage toxicity.
•History of autoimmune or inflammatory disorders.
•A current or prior use of immunosuppressive medication within 14 days of the 1st dose of study treatment.

Arms & Interventions

KN046

Intervention: KN046

Outcomes

Primary Outcomes

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).

Secondary Outcomes

Number of participants with adverse events (AEs)(From the time of informed consent signed through 90 days after the last dose of KN046，up to 2 years.)
Objective response rate (ORR)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
Duration of response (DoR)(up to 2 years.)
Progression-free survival (PFS)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
Clinical benefit rate (CBR)(From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.)
Area under the curve (AUC) of KN046(From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.)
Maximum observed concentration (Cmax) of KN046(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(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)(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)(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.)