Advanced Solid TumorsPhase 1NCT03529526
Study of the Safety, Tolerability, Pharmacokinetics, Immunogenicity and Antitumor Activity of KN046 in Subjects With Advanced Solid Tumors
A Phase 1 study testing KN046 in people with Advanced Solid Tumors, run by Alphamab (Australia) Co Pty Ltd. at 1 site in Australia.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- KN046
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteAustralia
- Study dates
- 21 May 2018to 30 Mar 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 1.
- 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.
Who cannot join
- 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.
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- 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.
- Suspected latent tuberculosis infection, confirmed by Mantoux test and a chest x-ray.
- 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
- 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.
- 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).
- History of severe allergic reactions to any unknown allergens or to parenteral administered recombinant protein product.
Trial locations and contacts
1 site in 1 country.
Australia1 site, 1 recruiting
- Recruiting
ICON Cancer Care
Southport, Queensland, 4125
Jermaine Coward, A/Prof, +61-07-3737-4500, jim.coward@gmail.com
Vinod Ganju
About this study
Official 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
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
- Conditions
- Advanced Solid Tumors
- Being tested
- KN046
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN046Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| KN046 | Experimental | Not described Receives: Drug: KN046 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: During the first cycle (4 weeks) of treatment.
Secondary outcomes (10)
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.
Measured: From the time of informed consent signed through 90 days after the last dose of KN046，up to 2 years.
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.
Measured: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
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.
Measured: up to 2 years.
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.
Measured: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
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.
Measured: From first dose of KN046 through 90 days after last dose of KN046, up to 2 years.
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.
Measured: From first dose of KN046 through 90 days after last dose of KN046, up to 9 months.
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.
Measured: 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
The endpoints for assessment of PK of KN046 include serum concentrations of KN046 at different timepoints after KN046 administration.
Measured: 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)
The immunogenicity of KN046 will be assessed by summarizing the number of subjects who develop detectable anti-drug antibodies (ADAs).
Measured: 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)
The neutralizing ADA will be assessed by summarizing the number of subjects who develop detectable neutralizing ADA .
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2018
- Study start21 May 2018 (estimated)
- Primary completion30 Oct 2019 (estimated)
- Study completion30 Mar 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Model description
- This is a dose-escalation trial, all participants will receive treatment with KN046. Participants enrolled in this trial may receive one of the following doses dependent upon time of enrolment into the study. Cohort 1: 0.3 mg/kg Cohort 2: 1 mg/kg Cohort 3: 3 mg/kg Cohort 4: 5 mg/kg Cohort 5: 10 mg/kg
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Alphamab (Australia) Co Pty Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03529526
- Sponsor's protocol ID
- KN046-AUS-001
- Status last verified
- May 2018
- First submitted
- 8 May 2018
- Last updated
- 22 May 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT03529526
- Acronym / sponsor ID
- KN046-AUS-001
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Alphamab (Australia) Co Pty Ltd.Industry (pharma, biotech, devices)
- Study start
- 21 May 2018 (estimated)
- Primary completion
- 30 Oct 2019 (estimated)
- Study completion
- 30 Mar 2020 (estimated)
- First posted
- 18 May 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a dose-escalation trial, all participants will receive treatment with KN046. Participants enrolled in this trial may receive one of the following doses dependent upon time of enrolment into the study. Cohort 1: 0.3 mg/kg Cohort 2: 1 mg/kg Cohort 3: 3 mg/kg Cohort 4: 5 mg/kg Cohort 5: 10 mg/kg
| Arm | Type | Receives |
|---|---|---|
| KN046 | Experimental | Drug: KN046 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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 1.
- 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.
Key exclusion criteria (15 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KN046The 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. | Drug | KN046 |
Primary outcome
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).
10 secondary outcomes
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.
Objective response rate (ORR)
Time frame: 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.
Progression-free survival (PFS)
Time frame: 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.
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.
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.
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.
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.
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2018.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing KN046 in people with Advanced Solid Tumors, run by Alphamab (Australia) Co Pty Ltd. at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jermaine Coward, A/Prof (+61-07-3737-4500, jim.coward@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose limiting toxicity (DLT) (time frame: During the first cycle (4 weeks) of treatment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2018.