Phase 1 Trial of KH801

A Phase I Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetic Characteristics, and Preliminary Anti-tumor Activity of KH801 Injection in Patients With Advanced Solid Tumors

KH801 is a injection used for advanced solid tumors which must be diluted with 5% Dextrose Or 0.9% sodium chloride Injection.

This study is expected to include a total of approximately 17-42 participants.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: KH801

• Study Type: Interventional
• Enrollment (Estimated): 17
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: ErWei Song; Phone Number: 18982182468; Email: 022516@cnkh.com
• Study Contact Backup: Name: Ling Song; Phone Number: 028-87516210; Email: songlin@cnkh.com

Study Locations

• China
  • Beijing
    • Peking, Beijing, China
      • Peking university cancer hospital
      • Principal Investigator: Lin Shen
      • Contact: Lin Shen
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital,Sun Yat-sen University
      • Principal Investigator: Herui Yao
      • Principal Investigator: ErWei Song
      • Contact: ErWei Song; Phone Number: 18982182468; Email: 022516@cnkh.com
      • Principal Investigator: Junyan Wu
  • Shandong
    • Jinan, Shandong, China
      • Central Hospital Affiliated To Shandong First Medical University
      • Contact: Meili Sun
      • Principal Investigator: Meili Sun
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • West China Second University Hospital,Sichuan University/West China Women's and Children's Hospital
      • Contact: Rutie Yin
      • Principal Investigator: Rutie Yin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent voluntarily.
2. Age ≥ 18 years old (subject to the date of signing the informed consent form), both genders.
3. With an expected life expectancy of ≥ 3 months.
4. With an ECOG（Eastern Cooperative Oncology Group Performance Status） performance status score of 0-1.
5. Patients with locally advanced unresectable or metastatic malignant solid tumors confirmed by histology, (including but not limited to breast cancer, lung cancer, ovarian cancer, colorectal cancer and other solid tumors) who failed or unable to tolerate previous standard treatments.
6. With at least one measurable target lesion was evaluated according to RECIST v1.1 criteria. Measurable target lesions were defined as non-lymph node lesions with the longest single diameter ≥ 10mm, or lymph node lesions with a short diameter ≥ 15mm.

7. The organ function reserve of patients before enrollment should meet the following laboratory test values:

   7.1 Hematology: Neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 90g/L, platelets ≥ 100 × 109/L ( Use of hematopoietic growth factor drugs within the first two weeks of screening is not allowed to improve the detection value and meet inclusion criteria); 7.2 Liver function: Total bilirubin ≤ 1.5 x ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN (if there is liver metastasis or hepatocellular carcinoma(HCC), ALT and AST ≤ 5 x ULN); 7.3 Renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance rate ≥ 50 milliliter（mL)/min (calculated using Cockcroft Gault formula, see Appendix 5 for details); Urinary protein<2+, or urinary protein ≥ 2+and 24-hour urine protein quantification<1g; 7.4 Coagulation function: prothrombin time (PT), international normalized ratio (INR), and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN (except for patients receiving anticoagulant therapy).

8. Female patients with fertility or male patients with partners with fertility must start using efficient contraceptive measures 7 days before the first dose and continue until 6 months after the last dose (excluding those who have undergone sterilization surgery (such as bilateral tubal ligation, oophorectomy, or hysterectomy). Female patients with fertility must have a negative blood pregnancy test within 7 days before the first administration.
9. Patients must recover from acute toxic reactions caused by previous anti-tumor treatments (CTCAE ≤ level 1), except for the following situations: a. hair loss; b. Skin pigmentation; c. Grade 2 ande below neurotoxicity; d. The long-term toxicity caused by radiotherapy cannot be restored according to the judgment of the researchers.

Exclusion Criteria:

1. Patients with primary central nervous system tumors and central nervous system (CNS) metastases (except for patients who have been clinically stable for ≥ 4 weeks after previous surgery or radiotherapy and have discontinued corticosteroid treatment).
2. Patients with interstitial lung disease (ILD) (excluding local interstitial pneumonia caused by radiotherapy), severe chronic obstructive pulmonary disease, and severe pulmonary insufficiency.
3. Positive for human immunodeficiency virus antibody (HIVAb), active hepatitis B virus infection (HBV-DNA copy number ≥ ULN) or active hepatitis C virus infection (HCV-RNA ≥ ULN), as well as other severe active infections that have not been controlled or require treatment.
4. Individuals who have previously received cluster of differentiation 24(CD24) targeted therapy.
5. Previous history of receiving allogeneic hematopoietic stem cell transplantation or other organ transplantation;
6. Patients who have received any anti-tumor treatment (including chemotherapy, hormone therapy, radiotherapy, immunotherapy, or biological therapy) within 4 weeks or 5 half lives of drugs previously used (whichever is longer) before the first dose.
7. Participated in other clinical trials within 4 weeks prior to the first administration.
8. Female subjects in lactation or pregnancy.
9. Previous or current mental/neurological disorders are not limited to schizophrenia, delusions, phobias, obsessive-compulsive disorder, Alzheimer's disease, behavioral and volitional disorders, postpartum mental disorders, paranoid mental disorders, and various organic disorders accompanied by mental disorders.
10. Active autoimmune diseases within the past 2 years (excluding vitiligo, Graves disease, Hashimoto's thyroiditis, or psoriasis that do not require systemic treatment).

11. Have suffered from other malignant tumors within the past 5 years, except for the following situations:

    11.1 Cured non melanoma skin malignant tumors; 11.2 Cervical carcinoma in situ; 11.3 Cured stage I endometrial cancer; 11.4 Curative breast ductal carcinoma in situ or lobular carcinoma in situ, and currently not receiving any systemic treatment; 11.5 Localized prostate cancer, papillary thyroid cancer, or follicular thyroid cancer that has undergone radical surgery and is currently considered cured/long-term stable.

12. Accompanied by active cardiovascular and cerebrovascular diseases:

    12.1 Has experienced myocardial infarction, stroke, bypass surgery, or stent placement within 6 months prior to the first administration; 12.2 Congestive heart failure New York Heart Association(NYHA) III-IV; 12.3 Left ventricular ejection fraction (LVEF)<50%; 12.4 Corrected QT interval(QTC) was prolonged (female>470ms, male>450ms); 12.5 Unstable angina that cannot be controlled by medication, severe arrhythmias that require medication treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia); 12.6 Hypertension (systolic blood pressure ≥ 160 millimeters of mercury (mmHg) or diastolic blood pressure ≥ 100mmHg) that cannot be controlled after standardized drug treatment, as well as a history of hypertensive crisis or hypertensive encephalopathy; 12.7 Suffering from major vascular diseases (such as aortic aneurysm, aortic dissection).

13. Patients with deep vein thrombosis (except for those with stable intermuscular vein thrombosis or infusion port thrombosis assessed by the investigators), pulmonary embolism or other serious thromboembolism, or patients with deep vein thrombosis, pulmonary embolism or other serious thromboembolism within 6 months before enrollment, and who are assessed by the investigator to be at risk of recurrence.
14. Patients allergic to immunoglobulin or any component of KH801 injection.
15. Patients who have received live attenuated vaccine within 4 weeks before enrollment or plan to receive live attenuated vaccine during the study period.
16. Patients who have undergone major surgery within 4 weeks before the first dose or plan to have major surgery during the study period.
17. Patients who have any other conditions that render them inappropriate for inclusion in the investigator's opinion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation; KH801 will be sequentially escalated at the dose of 0.01 mg/kg, 0.1 mg/kg, 0.3 mg/kg, 1.0 mg/kg , 3.0 mg/kg, 6.0 mg/kg , 10.0 mg/kg, administered via intravenous infusion every 2 weeks in 28-day treatment cycles.	Drug: KH801; KH801 is an injection solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MTD	Maximum tolerated dose (MTD)	up to 4 weeks
DLT	Dose limiting toxicity (DLT)	up to 4 weeks
RP2D	Recommended phase II dose (RP2D)	up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE	Adverse events	30 days after EOT,up to 1 year
Cmax	Maximum serum concentration (Cmax) of KH801 will be investigated	up to 12 weeks
Tmax	Time to maximum serum concentration(Tmax) of KH801 will be investigated	up to 12 weeks
T1/2	Half-life (T1/2) of KH801 will be investigated	up to 12 weeks
AUC0-t	AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration	up to 12 weeks
CL	Plasma clearance rate (Cl) is defined the volume of plasma per unit time in which drugs are completely eliminated.	up to 12 weeks
AUC0-inf	AUC0-inf is defined area under the blood drug concentration time curve from 0 to infinity	up to 12 weeks
anti-drug antibody (ADA)	The anti-drug antibody of KH801	up to 1 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate（ORR）	Objective Response Rate（ORR）is defined as the percentage of participants, who has a complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1	through study completion, an average of 1 year
Disease Control Rate (DCR)	The Disease Control Rate (DCR) is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]).	through study completion, an average of 1 year
Duration of Response (DOR)	The Duration of Response (DOR) for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.	through study completion, an average of 1 year
Median Progression-Free Survival (mPFS)	Median progression free survival (mPFS) refers to the progression free survival that 50% of assessable patients can achieve	through study completion, an average of 1 year
Overall Survival（OS)	The overall survival period refers to the time period from the start of treatment in a patient's study (whether randomized or single arm trial) until death from any cause	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Beijing Kanghong Biopharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2030

Study Registration Dates

• First Submitted: April 2, 2024
• First Submitted That Met QC Criteria: April 9, 2024
• First Posted (Actual): April 15, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: KH801

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No