The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03529526




Registration number
NCT03529526
Ethics application status
Date submitted
8/05/2018
Date registered
18/05/2018
Date last updated
22/05/2018

Titles & IDs
Public title
Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Antitumor Activity of KN046 in Subjects With Advanced Solid Tumors
Scientific title
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
Secondary ID [1] 0 0
KN046-AUS-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - KN046

Experimental: KN046 -


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with dose limiting toxicity (DLT) - 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).
Timepoint [1] 0 0
During the first cycle (4 weeks) of treatment.
Secondary outcome [1] 0 0
Number of participants with adverse events (AEs) - 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.
Timepoint [1] 0 0
From the time of informed consent signed through 90 days after the last dose of KN046,up to 2 years.
Secondary outcome [2] 0 0
Objective response rate (ORR) - The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.
Timepoint [2] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Secondary outcome [3] 0 0
Duration of response (DoR) - 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.
Timepoint [3] 0 0
up to 2 years.
Secondary outcome [4] 0 0
Progression-free survival (PFS) - 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.
Timepoint [4] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Secondary outcome [5] 0 0
Clinical benefit rate (CBR) - 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.
Timepoint [5] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
Secondary outcome [6] 0 0
Area under the curve (AUC) of KN046 - The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Timepoint [6] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Secondary outcome [7] 0 0
Maximum observed concentration (Cmax) of KN046 - The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Timepoint [7] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Secondary outcome [8] 0 0
Minimum observed plasma concentration (Ctrough) of KN046 at steady state - The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Timepoint [8] 0 0
From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
Secondary outcome [9] 0 0
Number of subjects who develop detectable anti-drug antibodies (ADAs) - The immunogenicity of KN046 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Timepoint [9] 0 0
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.
Secondary outcome [10] 0 0
Number of subjects who develop detectable neutralizing ADA (NADA) - The neutralizing ADA will be assessed by summarizing the number of subjects who develop detectable neutralizing ADA .
Timepoint [10] 0 0
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.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Unknown status
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
ICON Cancer Care - Southport
Recruitment postcode(s) [1] 0 0
4125 - Southport

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Alphamab (Australia) Co Pty Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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
Trial website
https://clinicaltrials.gov/show/NCT03529526
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Jermaine Coward, A/Prof
Address 0 0
Country 0 0
Phone 0 0
+61-07-3737-4500
Fax 0 0
Email 0 0
jim.coward@gmail.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03529526