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Trial details imported from ClinicalTrials.gov

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




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

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)
Timepoint [1] 0 0
During the first cycle (4 weeks) of treatment.
Secondary outcome [1] 0 0
Number of participants with adverse events (AEs)
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)
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)
Timepoint [3] 0 0
up to 2 years.
Secondary outcome [4] 0 0
Progression-free survival (PFS)
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)
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
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
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
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)
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)
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
Sex
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
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
Trial website
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
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.