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

Xuanzhu Biopharmaceutical Co., Ltd.1 site in 1 country96 target enrollmentApril 2023

ConditionsAdvanced Solid Tumors

InterventionsKM501

DrugsKM501

Overview

Phase: Phase 1
Intervention: KM501
Conditions: Advanced Solid Tumors
Sponsor: Xuanzhu Biopharmaceutical Co., Ltd.
Enrollment: 96
Locations: 1
Primary Endpoint: Recommended phase 2 dose (RP2D) (if has) (Part 1a)
Status: Not yet recruiting
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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

Registry

clinicaltrials.gov

Start Date

April 2023

End Date

December 2027

Last Updated

3 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Xuanzhu Biopharmaceutical Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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:
•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 ;

Exclusion Criteria

•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;
•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;

Arms & Interventions

KM501-1001

Intervention: KM501

Outcomes

Primary Outcomes

Recommended phase 2 dose (RP2D) (if has) (Part 1a)

Time Frame: Up to 4 weeks.

Determine Recommended Phase 2 dose (RP2D) of KM501

Maximum tolerated dose (MTD) (for Part 1a)

Time Frame: Up to 4weeks

Determine MTD of KM501

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

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

Secondary Outcomes

Disease control rate (DCR) (Part 1a and Part 1b)(up to 2-3 years.)
Progression free survival (PFS) (Part 1a and Part 1b)(up to 2-3 years.)
Anti-drug antibody(ADA )OF KM501 . (Part1a and Part1b)(up to 8months for Part1a and up to 2-3 years for Part1b.)
Objective response rate (ORR) (Part 1a)(Up to 8months.)
Serum Half-life (T-HALF) of KM501. (Part1a and Part1b)(Up to 63days.)
Area under the concentration versus time curve of KM501 in plasma (AUC)(Part 1a and Part1b).(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 ).(Up to 63days for Part 1a; Up to 63 days for Part1b.)
Overall survival (OS) (Part1a and Part1b )(up to 2-3 years)
Number of patients with adverse events (Part 1b)(up to 2-3 years.)