Advanced Solid TumorsPhase 1NCT04126590
Phase I Study of KN044 in Locally Advanced/Metastatic Solid Tumors
A Phase 1 study testing KN044 in people with Advanced Solid Tumors, run by Changchun Intellicrown Pharmaceutical Co. LTD at 1 site in China.
Trial summary
This is an open-label, multicenter, dose-escalation phase I study to assess the safety, tolerability and preliminary efficacy of KN044 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 to 75 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- KN044
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 39 participants
- Where
- 1 siteChina
- Study dates
- 9 Jan 2020to 1 Aug 2024
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects can understand informed consent, voluntarily participate and sign informed consent.
- Tumor subject type Clinical diagnosis of advanced malignant tumors. Patients diagnosed by pathology and/or cytology; malignant melanoma, patients with advanced renal cell carcinoma, colorectal cancer, lung cancer, breast cancer, prostate cancer, etc. are preferred; the inclusion of melanoma is pathological and / or cytologically undiagnosed unresectable patients with stage 3b/3c or stage 4 (M1a / M1b) melanoma, in which patients with stage IV M1b have to meet the following requirements: no more than 5; the longest path of a single lesion must not exceed 20 mm; the sum of the longest diameters of the cumulative lesions must not exceed 50 mm.
- Subjects with locally advanced (non-resectable) and / or metastatic solid tumor that has progressed after standard therapies or no standard therapy exists.
- Previous anti-tumor therapy (including endocrine chemoradiotherapy/radiotherapy, targeted therapy) ended more than 4 weeks and has been restored to baseline or ≤ grade 1 from previous adverse events following [Common Criteria for Assessment of Adverse Events (CTCAE) version 5.0] (except for patients with hair loss).
- 18-75 years of age, male or female; 10)Eastern Cooperative Oncology Group score 0 or 2; Life expectancy ≥ 3 months.
- Previous major surgery ≥1 month ago.
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- Must have adequate organ function, prior to start of KN044, including the following:
- white blood cell count ≥ 3.0 × 109 / L;
- absolute neutrophil count (ANC) ≥ 1.5 ×109/L;
- platelet count ≥ 100 × 109/L;
- hemoglobin ≥ 9 g/dL
- serum albumin ≥ 2.5 g / dL;
- Hepatic: total bilirubin ≤ 1.5 times the upper limit of normal (ULN); aspartate transaminase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5× ULN (≤5 × ULN if with liver involvement)
- Renal: Serum creatinine ≤ 1.5×ULN or 24-hour Estimated clearance≥50 mL / min (Cockcroft and Gault formula);
- Coagulation tests International standardization ratio (INR) ≤ 1.5, prothrombin time (PT), activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN
- Normal left ventricular ejection fraction (LVEF) ≥50% measured by multigated radionuclide angiography or Echocardiography.
- Female patient with fertility or male patient whose partner has fertility should use one or more contraceptive methods for contraception within at least eight months from the screening period to five half-lives after the last treatment. These measures include, but are not limited to, oral or implantable injections of hormonal contraceptives; intrauterine birth control ring or placement of hormone-releasing intrauterine device); or use of barrier methods such as condoms or septum and spermicide products.
- According to ResponseEvaluationCriteriainSolid Tumors Version1.1, the subject should have an assessable lesion (target lesion or non-target lesion)
- grade ≤ 2 peripheral neuropathy can be enrolled
Who cannot join
- At the discretion of the investigator, there are both serious medical conditions that may harm the safety of the subject or affect the subject's completion of the study, including but not limited to: severe heart disease, cerebrovascular disease, uncontrolled diabetes, Insulin dependent diabetes, serious infection;Thyroid disease
- Accepted any other anti-tumor drug therapies, or other immunological anti-tumor treatments, including but not limited to PD-1/L1 inhibitors before the first KN044 dosing.
- Pregnant or nursing females
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure New York Heart Association III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, ECG QT interval（fridericia)> 450msec, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)；Hypertension (defined as sustained systolic blood pressure> 150 mm Hg and / or post-diastolic blood pressure with antihypertensive drugs> 100 mm Hg;
- suffering from mental disorders, infectious diseases, and skin diseases that are difficult to control;
- Known active hepatitis B or C or known infection with HIV .
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- History of life-threatening hypersensitivity, or known to be allergic to protein drugs or recombinant proteins or any ingredients in KN044 drug formulation
- Known severe bleeding factors that can affect venous blood sampling;
- Acute or chronic uncontrolled renal disease, pancreatitis or liver disease (per investigator assessment).
- Subjects with active autoimmune disease or a documented medical history of autoimmune disease or symptoms that require systemic use of steroid and/or immunosuppressant. Exceptions are subjects with vitiligo, resolved childhood asthma/atopy, type I diabetes mellitus or hypothyroidism which can be managed by replacement therapy.
- Use of more than 15 mg of prednisone or equivalent dose of steroids per day within 3 months of administration.
- Electrocardiogram QT interval (fridericia) > 450 msec and severe arrhythmia requiring medication (except for atrial fibrillation or paroxysmal supraventricular tachycardia);
- Uncontrolled primary central nervous system tumors or central nervous system metastasis; based on screening brain magnetic resonance imaging (MRI), patients who have one of the following may not be excluded:
- No evidence of brain metastases or has to be clinically stable for at least 4 weeks
- Untreated brain metastases not needing immediate local therapy
- Live vaccines are banned 30 days prior to enrollment and during clinical studies. Inactive vaccines are allowed during the study;
- Within 30 days prior to screening, the patient has undergone any other experimental drug therapy or has participated in another interventional clinical trial;
- The study may not be completed for other reasons or the Investigators believes that it should not be included;
- Peripheral neuropathy >Grade 2.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100000
Rui Chen
About this study
Official title: Phase I Clinical Study of Safety，Tolerability， Pharmacokinetics and Pharmacodynamics of Recombinant Humanized Cytotoxic T Lymphocyte Antigen 4 Single Domain Antibody Fc Fusion Protein Injection 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 KN044 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) , to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN044 as a single agent in adult participants with advanced solid tumors.
Read the detailed description
This study will involve patients and follow the standard "3 + 3"design. KN044 will be antimedical intravenously over 30 minutes with planned doses of 0.03, 0.1, 0.3, 1, 3, 6,10 mg/kg Once every 3 weeks for first 4 doses, then every 3, or 6, or 12 weeks for up to 1 year if no intolerable toxicities occur and per agreement with investigator antimedical monitor based on emerging data.
- Conditions
- Advanced Solid Tumors
- Being tested
- KN044
- Keywords
- Adverse Event, Anti-Drug Antibodies, Complete Response
- Medical subject headings
- Pathologic Complete Response
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KN044Biological
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 KN044: 0.03mg/kg,0.3 mg/kg,1 mg/kg,3 mg/kg,6 mg/kg,10 mg/kg.
| Study group | Role | What they receive |
|---|---|---|
| KN044 0.03 mg/kg dose group | Experimental | KN044 0.03 mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 0.1 mg/kg dose group | Experimental | KN044 0.1 mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 0.3mg/kg dose group | Experimental | KN044 0.3mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 1 mg/kg dose group | Experimental | KN044 1 mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 3 mg/kg dose group | Experimental | KN044 3 mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 6mg/kg dose group | Experimental | KN044 6mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
| KN044 10mg/kg dose group | Experimental | KN044 10mg/kg dose group,once every 3 weeks，a total of four cycles Receives: Biological: KN044 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity for The maximum tolerated dose
Dose-limiting toxicity observation period 6 weeks after the first dose
Measured: up to 6 weeks
KN044 of adverse event
the adverse events are recorded according to the actual occurrence
Measured: through study completion, an average of 210 days
KN044 of abnormalities of physical findings and laboratory tests,
The data of the clinical research center is collected and analyzed according to the time point of the test flow chart
Measured: through study completion, an average of 210 days
Secondary outcomes (8)
PK parameters: Area under curve (AUC)
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
PK parameters: Cmax
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
PK parameters: Clearance rate (CL)
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
PK parameters: t1/2
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
PK parameters: Vss
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
PK parameters: dose proportionality
According to the test schedule, the blood volume of each subject's PK was analyzed and PK analysis was performed.
Measured: an average of 126 days
Incidence of the positive anti-drug antibodies and titers of anti-drug antibodies
According to the test schedule, the blood volume of each subject's anti-drug antibodies was analyzed and anti-drug antibodies analysis was performed.
Measured: an average of 147 days
Anti-tumor activity as measured by ResponseEvaluationCriteriainSolidTumors Version1.1(RESISTv1.1)
Evaluation of tumor response according to RESISTv1.1 criteria, complete relief（CR), Partial relief(PR), Stable disease(SD), PD、ORR[CR＋PR]）、Disease control rate(DCR[CR＋PR＋SD]）、PFS、DOR
Measured: During the treatment period , the tumor was evaluated every 6 weeks, then every 9 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2019
- Study start9 Jan 2020
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Aug 2024 (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
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 39 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Changchun Intellicrown Pharmaceutical Co. LTD
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- chunmei Bai, Principal investigator, Peking Union Medical College HospitalRui Chen, Principal investigator, Peking Union Medical College Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04126590
- Sponsor's protocol ID
- KN0440101a
- Status last verified
- Aug 2023
- First submitted
- 10 Oct 2019
- Last updated
- 1 Sep 2023
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Study of Safety，Tolerability， Pharmacokinetics and Pharmacodynamics of Recombinant Humanized Cytotoxic T Lymphocyte Antigen 4 Single Domain Antibody Fc Fusion Protein Injection in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04126590
- Acronym / sponsor ID
- KN0440101a
- Conditions
- Advanced Solid Tumors
- Keywords
- Adverse Event, Anti-Drug Antibodies, Complete Response
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 39 participants (estimated)
- Lead sponsor
- Changchun Intellicrown Pharmaceutical Co. LTDIndustry (pharma, biotech, devices)
- Study start
- 9 Jan 2020 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Aug 2024 (estimated)
- First posted
- 15 Oct 2019 (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 KN044 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) , to characterise the safety, pharmacokinetics (PK), immunogenicity, pharmacodynamics (PD) and anti-tumor activity of KN044 as a single agent in adult participants with advanced solid tumors.
Detailed description
This study will involve patients and follow the standard "3 + 3"design. KN044 will be antimedical intravenously over 30 minutes with planned doses of 0.03, 0.1, 0.3, 1, 3, 6,10 mg/kg Once every 3 weeks for first 4 doses, then every 3, or 6, or 12 weeks for up to 1 year if no intolerable toxicities occur and per agreement with investigator antimedical monitor based on emerging data.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| KN044 0.03 mg/kg dose group | Experimental | Biological: KN044KN044 0.03 mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 0.1 mg/kg dose group | Experimental | Biological: KN044KN044 0.1 mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 0.3mg/kg dose group | Experimental | Biological: KN044KN044 0.3mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 1 mg/kg dose group | Experimental | Biological: KN044KN044 1 mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 3 mg/kg dose group | Experimental | Biological: KN044KN044 3 mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 6mg/kg dose group | Experimental | Biological: KN044KN044 6mg/kg dose group,once every 3 weeks，a total of four cycles |
| KN044 10mg/kg dose group | Experimental | Biological: KN044KN044 10mg/kg dose group,once every 3 weeks，a total of four cycles |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects can understand informed consent, voluntarily participate and sign informed consent.
- Tumor subject type Clinical diagnosis of advanced malignant tumors. Patients diagnosed by pathology and/or cytology; malignant melanoma, patients with advanced renal cell carcinoma, colorectal cancer, lung cancer, breast cancer, prostate cancer, etc. are preferred; the inclusion of melanoma is pathological and / or cytologically undiagnosed unresectable patients with stage 3b/3c or stage 4 (M1a / M1b) melanoma, in which patients with stage IV M1b have to meet the following requirements: no more than 5; the longest path of a single lesion must not exceed 20 mm; the sum of the longest diameters of the cumulative lesions must not exceed 50 mm.
- Subjects with locally advanced (non-resectable) and / or metastatic solid tumor that has progressed after standard therapies or no standard therapy exists.
- Previous anti-tumor therapy (including endocrine chemoradiotherapy/radiotherapy, targeted therapy) ended more than 4 weeks and has been restored to baseline or ≤ grade 1 from previous adverse events following [Common Criteria for Assessment of Adverse Events (CTCAE) version 5.0] (except for patients with hair loss).
- 18-75 years of age, male or female; 10)Eastern Cooperative Oncology Group score 0 or 2; Life expectancy ≥ 3 months.
Key exclusion criteria (19 listed)
- At the discretion of the investigator, there are both serious medical conditions that may harm the safety of the subject or affect the subject's completion of the study, including but not limited to: severe heart disease, cerebrovascular disease, uncontrolled diabetes, Insulin dependent diabetes, serious infection;Thyroid disease
- Accepted any other anti-tumor drug therapies, or other immunological anti-tumor treatments, including but not limited to PD-1/L1 inhibitors before the first KN044 dosing.
- Pregnant or nursing females
- Severe or uncontrolled cardiac disease requiring treatment, congestive heart failure New York Heart Association III or IV, unstable angina pectoris even if medically controlled, history of myocardial infarction during the last 6 months, ECG QT interval（fridericia)> 450msec, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia)；Hypertension (defined as sustained systolic blood pressure> 150 mm Hg and / or post-diastolic blood pressure with antihypertensive drugs> 100 mm Hg;
- suffering from mental disorders, infectious diseases, and skin diseases that are difficult to control;
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 |
|---|---|---|
| KN044The 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 KN044: 0.03mg/kg,0.3 mg/kg,1 mg/kg,3 mg/kg,6 mg/kg,10 mg/kg. | Biological | KN044 0.03 mg/kg dose group, KN044 0.1 mg/kg dose group, KN044 0.3mg/kg dose group, KN044 1 mg/kg dose group, KN044 10mg/kg dose group, KN044 3 mg/kg dose group, KN044 6mg/kg dose group |
Primary outcome
Dose-limiting toxicity for The maximum tolerated dose
Time frame: up to 6 weeks
Dose-limiting toxicity observation period 6 weeks after the first dose
KN044 of adverse event
Time frame: through study completion, an average of 210 days
the adverse events are recorded according to the actual occurrence
KN044 of abnormalities of physical findings and laboratory tests,
Time frame: through study completion, an average of 210 days
The data of the clinical research center is collected and analyzed according to the time point of the test flow chart
8 secondary outcomes
PK parameters: Area under curve (AUC)
Time frame: an average of 126 days
PK parameters: Cmax
Time frame: an average of 126 days
PK parameters: Clearance rate (CL)
Time frame: an average of 126 days
PK parameters: t1/2
Time frame: an average of 126 days
PK parameters: Vss
Time frame: an average of 126 days
PK parameters: dose proportionality
Time frame: an average of 126 days
Incidence of the positive anti-drug antibodies and titers of anti-drug antibodies
Time frame: an average of 147 days
Anti-tumor activity as measured by ResponseEvaluationCriteriainSolidTumors Version1.1(RESISTv1.1)
Time frame: During the treatment period , the tumor was evaluated every 6 weeks, then every 9 weeks.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2023.
- 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.
chunmei Bai principal investigator
Peking Union Medical College Hospital
Rui Chen principal investigator
Peking Union Medical College Hospital
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 KN044 in people with Advanced Solid Tumors, run by Changchun Intellicrown Pharmaceutical Co. LTD at 1 site in China.
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 19 inclusion and 19 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 1 Sep 2023. 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 China. 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 Shiqi Bai (18943642700, baishiqi@intelli-crown.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity for The maximum tolerated dose (time frame: up to 6 weeks). The study lists 3 primary outcomes in all. 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 1 Sep 2023.