Advanced Solid TumorsPhase 1NCT05804864
A Study of KM501 in Patients With Solid Tumors
A Phase 1 study testing KM501 in people with Advanced Solid Tumors, run by Xuanzhu Biopharmaceutical Co., Ltd. at 1 site in China.
Trial summary
A single-arm, open, multicenter Phase I study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of the KM501 double-antibody ADC in subjects with advanced solid tumors that express, amplify, or mutate HER2 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?
- KM501
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- 1 siteChina
- Study dates
- Apr 2023to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Voluntarily sign informed consent;
- At least 18 years old and less than 75 years old on the date of signing the informed consent;
- Subjects with histologically or cytologically confirmed advanced solid tumors who have developed disease progression since the last antitumor therapy, have no standard therapy available, do not tolerate or refuse standard therapy;
- Stage Ia: Subjects with advanced relapsed or metastatic solid tumors with HER2 expression or amplification or mutation, stage Ia may refer to (but is not limited to) specific types of tumors at stage Ib;
- Stage Ib: HER2-positive or expressed advanced breast cancer, advanced urothelial cancer, advanced gastric cancer or gastroesophageal junction adenocarcinoma, advanced ovarian cancer, and advanced endometrial cancer; Wild-type unresectable RAS and BRAF with HER2 expression or amplification in locally advanced or metastatic colorectal cancer; Advanced non-small cell lung cancer with a HER2 mutation. Other advanced tumors that are HER2-positive or expressed, HER2 amplified or mutated may be determined after discussion with the sponsor.
- The subject shall provide a previous HER2 test report. If there is no previous HER2 test result, the archived/biopsied tumor tissue shall be provided for HER2 test in a 3A hospital or central laboratory. The HER2 status of the tumor tissue was determined by the investigator based on previous reports and test results from a 3A hospital or central laboratory. HER2 status is as follows:
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- HER2 expression: IHC(3+), IHC(2+) or IHC(+);
- HER2 positive: IHC(3+) or IHC(2+) further test positive for ISH;
- HER2 amplification: ISH positive or NGS/PCR confirmed HER2 amplification; • HER2 mutation: A HER2 mutation identified by NGS/PCR/Sanger sequencing.
- The ECOG physical status score is 0 or 1 ;
- Lesion requirements: Stage Ia subjects need to have evaluable lesions; Stage Ib subjects must have at least one measurable target lesion. For targets previously treated with radiation, a measurable lesion is considered only if there is definite progression [see Appendix 3 for the definition of measurable lesions in solid tumors].
- Expected survival ≥12 weeks; 8. Within 7 days prior to initial drug administration, subjects must meet the following laboratory test values to ensure adequate organ and hematopoietic function (no blood transfusion, erythropoietin, granulocyte colony stimulating factor and other hematopoietic growth factor treatment, hepatoprotective therapy or other medical support treatment within 2 weeks prior to initial drug administration).
- 9. A man or woman with reproductive potential must consent to the use of effective contraceptive methods starting with the signing of an informed consent form and continuing for six months from the end of the study treatment (Appendix 6). Pregnancy tests for women of reproductive age must be negative within 7 days of the first trial drug administration (fertility potential defined as premenopausal women who have not had a tubal ligation or hysterectomy, or within 1 year after menopause).
Who cannot join
- Subjects with known clinical or untreated central nervous system metastases, including meningeal metastases. Does not include: After radiation therapy, MRI/CT examination at least 4 weeks prior to initial administration of the trial drug (showing stable lesions, no uncontrollable neurological symptoms or signs (e.g., epilepsy, headache, central nausea/vomiting, progressive neurological dysfunction, papilledema), or any treatment that does not require local (e.g., radiation) and systemic (e.g., Untreated asymptomatic brain metastases of mannitol or corticosteroids;
- Subjects with other malignancies within 5 years prior to initial administration of the experimental drug, except those with basal cell carcinoma, local squamous cell carcinoma of the skin, cervical carcinoma in situ, etc., who have not relapsed and metastasized after radical treatment;
- Subjects who have received chemotherapy, targeted therapy, or other systematic antitumor therapy within 4 weeks or 5 half-lives (whichever is older) prior to the initial administration of the test drug, and who have been treated with Chinese herbal or proprietary drugs for antitumor purposes within 2 weeks prior to the initial administration;
- Subjects who required systematic treatment with a dose of a corticosteroid >10 mg/ day equivalent to prednisone (see Appendix 9 for dose conversion) or other immunosuppressant within 14 days prior to initial administration of the trial drug or during the study period. Inhaled or topical doses ≤10 mg/ day equivalent to prednisone are permitted in the absence of active autoimmune disease. Short-term use of corticosteroids in doses >10 mg/ day equivalent to prednisone is permitted for the prevention (e.g., contrast allergy) or treatment of non-autoimmune diseases (e.g., delayed hypersensitivity caused by exposure to allergens);
- Subjects who received major surgery (as determined by the investigator) or radical radiation therapy within 4 weeks prior to initial administration of the test drug; Or received palliative radiotherapy within 2 weeks prior to initial administration of the trial drug; Or received radioactive agents (strontium, samarium, etc.) for therapeutic purposes within 8 weeks prior to the first dosing of the test drug;
- Subjects who have received other investigational drugs or treatments within 4 weeks prior to initial administration of the investigational drug;
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- ILD (non-infectious) interstitial lung disease (ILD) requiring glucocorticosteroid treatment/or current clinically significant active or current ILD/ pneumonia, or suspicious ILD/ pneumonia that cannot be excluded by imaging during screening;
- Subjects with a known history of human immunodeficiency virus (HIV) infection; Laboratory test value: ANC≥ 1.5×109/L; PLT≥ 100×109/L Hb≥ 90 g/L ; CR≤1.5 times the upper limit of normal range (ULN) and creatinine clearance ≥60 mL/min (calculated according to Cockcroft-Gault formula); T-BIL ≤ 1.5 times ULN; ALT and AST Stage Ia: ≤ 2.5 times ULN;Stage Ib: ≤ 2.5 ULN, or ≤5 ULN (for subjects with liver metastases); INR and PT≤ 1.5 times ULN; APTT≤ 1.5 times ULN;
- Active hepatitis B virus (HBsAg positive and/or HBcAb positive with HBV-DNA> upper limit of quantification) or hepatitis C virus infection (HCV antibody positive and HCV RNA positive);
- Active infections requiring systematic treatment, including active tuberculosis, within 2 weeks prior to initial administration of the experimental drug;
- Pleural effusion, pericardial effusion, and abdominal effusion that could not be controlled by appropriate intervention were present within 4 weeks prior to initial administration of the test drug (note: Subjects with small amounts of effusion that could only be detected by imaging examination could be included);
- Subjects who have received previous organ transplants;
- Toxicity associated with previous antitumor therapy did not return to grade 1 or less (NCI-CTCAE v5.0) (except for alopecia, grade 2 hypoparathyroidism, or toxicity judged by the investigator to be of no safety risk);
- Subjects with active gastrointestinal bleeding, intestinal obstruction, intestinal paralysis, glaucoma, uncontrolled diabetes and other serious concomitant diseases;
- Subjects with a known history of alcohol or drug abuse;
- Subjects with significant cardiovascular disease: Subjects with severe arrhythmias, acute myocardial ischemia, unstable angina pectoris, congestive heart failure (NYHA grade ≥ 2 (Appendix 5)), left ventricular ejection fraction (LVEF) <50% within 6 months prior to initial administration of the experimental drug, Subjects with a history of long QT syndrome or a confirmed family history of long QT syndrome had heart-rate adjusted QTcF intervals of > 450 msec (male) and > 470 msec (female) using the Fridericia formula (Appendix 7);
- Uncontrolled hypertension with standard treatment (systolic blood pressure ≥140 and/or diastolic blood pressure ≥90 mmHg);
- History of cerebrovascular accidents, including transient ischemic attack or stroke, within 6 months prior to initial administration of the experimental drug;
- Subjects with stage Ib colorectal cancer: subjects with known activating mutations in exons 2, 3, and 4 of KRAS/NRAS and V600E of BRAF (except those who are assessed to benefit by the investigator);
- Subjects with a history of grade 2 or above peripheral nerve disease;
- People who are known to be allergic to recombinant humanized anti-HER-2 bispecific antibody -MMAE conjugate drug and its components (L-histidine, histidine hydrochloride, polysorbate 80, etc.);
- Previous history of hypersensitivity, angioedema or severe hypotension caused by Herceptin or pertuzumab or biosimilar drugs;
- Subjects with a known mental illness that may affect compliance with the test;
- Pregnant women (positive pregnancy test before medication) or lactating women;
- The investigator considers that the subject is ineligible to participate in the clinical study for any clinical or laboratory abnormality or other reason.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Tianjin Cancer Hospital
Tianjin, Tianjin Municipality, 300060
Yi Ba, Doctor, +86-022-23340123-6416, tjmuchxhnk@126.com
About this study
Official title: A Single-arm, Open, Multicenter Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Efficacy of the KM501 Double-antibody ADC in Subjects With Advanced Solid Tumors That Express, Amplify, or Mutate HER2
A single-arm, open, multicenter Phase I study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of the KM501 double-antibody ADC in subjects with advanced solid tumors that express, amplify, or mutate HER2
- Conditions
- Advanced Solid Tumors
- Being tested
- KM501
- Keywords
- KM501, ADC
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KM501Drug
1a: The program evaluated six dose levels, i.e., 0.1, 0.3, 0.6, 1.2, 1.8, 2.4 mg/kg, An accelerated titration was performed in the 0.1 and 0.3 mg/kg dose groups, and then a Bayesian optimal interval design was used to determine MTDS for four subsequent dose levels. Ib: The antitumor activity of KM501 monotherapy in subjects with specific types of tumors that are HER2-positive or express, amplify, or mutate will be evaluated at the RP2D dose level
| Study group | Role | What they receive |
|---|---|---|
| KM501-1001 | Experimental | Not described Receives: Drug: KM501 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) (for Part 1a)
Determine MTD of KM501
Measured: Up to 4weeks
Recommended phase 2 dose (RP2D) (if has) (Part 1a)
Determine Recommended Phase 2 dose (RP2D) of KM501
Measured: Up to 4 weeks.
Number of participants with treatment-related adverse events （Part 1a）
Incidence of AE as assessed by CTCAE 5.0
Measured: Up to 8 months.
Objective response rate (ORR) (Part 1b)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: Up to 2-3 years.
Secondary outcomes (9)
Area under the concentration versus time curve of KM501 in plasma (AUC)(Part 1a and Part1b).
To determine the area under the plasma concentration time curve (AUC) of KM501
Measured: Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.
Maximum plasma concentration (Cmax) of KM501(Part 1a and Part 1b ).
Cmax is the maximum observed plasma concentration in ng/mL
Measured: Up to 63days for Part 1a; Up to 63 days for Part1b.
Serum Half-life (T-HALF) of KM501. (Part1a and Part1b)
To determine the t1/2 of KM501.
Measured: Up to 63days.
Anti-drug antibody(ADA )OF KM501 . (Part1a and Part1b)
To determine the immunogenicity of KM501.
Measured: up to 8months for Part1a and up to 2-3 years for Part1b.
Objective response rate (ORR) (Part 1a)
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Measured: Up to 8months.
Progression free survival (PFS) (Part 1a and Part 1b)
To determine the PFS by investigator.
Measured: up to 2-3 years.
Disease control rate (DCR) (Part 1a and Part 1b)
To determine the DCR by investigator.
Measured: up to 2-3 years.
Overall survival (OS) (Part1a and Part1b )
To determine the OS by investigator.
Measured: up to 2-3 years
Number of patients with adverse events (Part 1b)
Incidence of AE as assessed by CTCAE 5.0
Measured: up to 2-3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2023
- Study startApr 2023 (estimated)
- Primary completionDec 2026 (estimated)
- Study completionDec 2027 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xuanzhu Biopharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Yi Ba, Principal investigator, Tianjin Cancer Hospital Airport Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05804864
- Sponsor's protocol ID
- KM501-1001
- Status last verified
- Apr 2023
- First submitted
- 12 Mar 2023
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open, Multicenter Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetic Profile, and Efficacy of the KM501 Double-antibody ADC in Subjects With Advanced Solid Tumors That Express, Amplify, or Mutate HER2
- ClinicalTrials.gov ID
- NCT05804864
- Acronym / sponsor ID
- KM501-1001
- Conditions
- Advanced Solid Tumors
- Keywords
- KM501, ADC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- Xuanzhu Biopharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- Apr 2023 (estimated)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 7 Apr 2023 (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.
A single-arm, open, multicenter Phase I study to evaluate the safety, tolerability, pharmacokinetic profile, and efficacy of the KM501 double-antibody ADC in subjects with advanced solid tumors that express, amplify, or mutate HER2
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KM501-1001 | Experimental | Drug: KM501 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Voluntarily sign informed consent;
- At least 18 years old and less than 75 years old on the date of signing the informed consent;
- Subjects with histologically or cytologically confirmed advanced solid tumors who have developed disease progression since the last antitumor therapy, have no standard therapy available, do not tolerate or refuse standard therapy;
- The subject shall provide a previous HER2 test report. If there is no previous HER2 test result, the archived/biopsied tumor tissue shall be provided for HER2 test in a 3A hospital or central laboratory. The HER2 status of the tumor tissue was determined by the investigator based on previous reports and test results from a 3A hospital or central laboratory. HER2 status is as follows:
- The ECOG physical status score is 0 or 1 ;
Key exclusion criteria (25 listed)
- Subjects with known clinical or untreated central nervous system metastases, including meningeal metastases. Does not include: After radiation therapy, MRI/CT examination at least 4 weeks prior to initial administration of the trial drug (showing stable lesions, no uncontrollable neurological symptoms or signs (e.g., epilepsy, headache, central nausea/vomiting, progressive neurological dysfunction, papilledema), or any treatment that does not require local (e.g., radiation) and systemic (e.g., Untreated asymptomatic brain metastases of mannitol or corticosteroids;
- Subjects with other malignancies within 5 years prior to initial administration of the experimental drug, except those with basal cell carcinoma, local squamous cell carcinoma of the skin, cervical carcinoma in situ, etc., who have not relapsed and metastasized after radical treatment;
- Subjects who have received chemotherapy, targeted therapy, or other systematic antitumor therapy within 4 weeks or 5 half-lives (whichever is older) prior to the initial administration of the test drug, and who have been treated with Chinese herbal or proprietary drugs for antitumor purposes within 2 weeks prior to the initial administration;
- Subjects who required systematic treatment with a dose of a corticosteroid >10 mg/ day equivalent to prednisone (see Appendix 9 for dose conversion) or other immunosuppressant within 14 days prior to initial administration of the trial drug or during the study period. Inhaled or topical doses ≤10 mg/ day equivalent to prednisone are permitted in the absence of active autoimmune disease. Short-term use of corticosteroids in doses >10 mg/ day equivalent to prednisone is permitted for the prevention (e.g., contrast allergy) or treatment of non-autoimmune diseases (e.g., delayed hypersensitivity caused by exposure to allergens);
- Subjects who received major surgery (as determined by the investigator) or radical radiation therapy within 4 weeks prior to initial administration of the test drug; Or received palliative radiotherapy within 2 weeks prior to initial administration of the trial drug; Or received radioactive agents (strontium, samarium, etc.) for therapeutic purposes within 8 weeks prior to the first dosing of the test drug;
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 |
|---|---|---|
| KM5011a: The program evaluated six dose levels, i.e., 0.1, 0.3, 0.6, 1.2, 1.8, 2.4 mg/kg, An accelerated titration was performed in the 0.1 and 0.3 mg/kg dose groups, and then a Bayesian optimal interval design was used to determine MTDS for four subsequent dose levels. Ib: The antitumor activity of KM501 monotherapy in subjects with specific types of tumors that are HER2-positive or express, amplify, or mutate will be evaluated at the RP2D dose level | Drug | KM501-1001 |
Primary outcome
Maximum tolerated dose (MTD) (for Part 1a)
Time frame: Up to 4weeks
Determine MTD of KM501
Recommended phase 2 dose (RP2D) (if has) (Part 1a)
Time frame: Up to 4 weeks.
Determine Recommended Phase 2 dose (RP2D) of KM501
Number of participants with treatment-related adverse events （Part 1a）
Time frame: Up to 8 months.
Incidence of AE as assessed by CTCAE 5.0
Objective response rate (ORR) (Part 1b)
Time frame: Up to 2-3 years.
Number of participants who achieved a best response of either complete response (CR) or partial response (PR) during treatment evaluated by investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
9 secondary outcomes
Area under the concentration versus time curve of KM501 in plasma (AUC)(Part 1a and Part1b).
Time frame: Up to 8 months for Part 1a; Up to 2 to 3 years for Part1b.
Maximum plasma concentration (Cmax) of KM501(Part 1a and Part 1b ).
Time frame: Up to 63days for Part 1a; Up to 63 days for Part1b.
Serum Half-life (T-HALF) of KM501. (Part1a and Part1b)
Time frame: Up to 63days.
Anti-drug antibody(ADA )OF KM501 . (Part1a and Part1b)
Time frame: up to 8months for Part1a and up to 2-3 years for Part1b.
Objective response rate (ORR) (Part 1a)
Time frame: Up to 8months.
Progression free survival (PFS) (Part 1a and Part 1b)
Time frame: up to 2-3 years.
Disease control rate (DCR) (Part 1a and Part 1b)
Time frame: up to 2-3 years.
Overall survival (OS) (Part1a and Part1b )
Time frame: up to 2-3 years
Number of patients with adverse events (Part 1b)
Time frame: up to 2-3 years.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
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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.
Yi Ba principal investigator
Tianjin Cancer Hospital Airport 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 KM501 in people with Advanced Solid Tumors, run by Xuanzhu Biopharmaceutical 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 13 inclusion and 25 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: opening soon, as of the sponsor's last update on 7 Apr 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cuilan Xiao (+86-13699167610, xiaocuilan@xuanzhubio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (for Part 1a) (time frame: Up to 4weeks). The study lists 4 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 7 Apr 2023.