Phase I Study of KN035 in Chinese Subjects With Advanced Solid Tumors

NCT03101488 | Completed Phase 1 DMC

• 1 other identifier: KN035-CN-001
• Study Type: interventional
• Target: 287
• Locations: 1 country
• Sites: 4

Brief Summary

This dose escalation and dose expansion study is to evaluate and characterize the tolerability and safety profile of single agent KN035 in Chinese adult subjects with unresectable advanced carcinoma.

Conditions

Solid Tumors

Keywords

KN035; phase 1

Outcome Measures

Primary Outcomes (3)

• Incidence of dose limiting toxicities (DLTs) in dose escalation study

  From screening to up to cycle 1 (28 days)

• Percentage of participants with adverse events (AEs), serious adverse events and AEs of special interest

  From screening to up to 1 months after the last dose of study drug (up to approximately 2 years)

• ORR of HCC patients in dose expansion study

  Up to 2 approximately years

Secondary Outcomes (18)

• Peak Plasma Concentration (Cmax) of KN035 in Chinese patients

  From Pre-dose of the first dose to up to cycle 12

• Peak Time (Tmax) of KN035 in Chinese patients

  From Pre-dose of the first dose to up to cycle 12

• Area under the plasma concentration versus time curve (AUC) of KN035 in Chinese patients

  From Pre-dose of the first dose to up to cycle 12

• t1/2 of KN035 in Chinese patients

  From Pre-dose of the first dose to up to cycle 12

• Trough concentration of KN035 in Chinese patients

  From Pre-dose of the first dose to up to cycle 12

Study Arms (1)

KN035

EXPERIMENTAL

KN035 is to be injected subcutaneously 0.1mg/kg or 0.3mg/kg or 1mg/kg or 2.5mg/kg or 5mg/kg or 10mg/kg weekly until disease progresses or unacceptable tolerability occurs.

Drug: KN035

Interventions

KN035 DRUG

KN035 is a monoclonal antibody drug which is formulated for subcutaneous injection in a single-use vial (brown neutral borosilicate) containing a total of 300 mg antibody in 1.5 ml of solution.

KN035

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is male or female ≥ 18 years and ≤ 70 years of age on the day of signing informed consent,and subject has voluntarily agreed to participate by giving written informed consent.
• Subjects must have a histopathological diagnosis of any locally advanced or metastatic solid tumor, Subjects must have failed established standard medical anti-cancer therapies ( have disease progression after the therapies or be intolerant to the therapies) or Subjects refuse to standard therapies, or no effective treatment.
• Measurable disease as defined by RECIST v1.1.
• Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Life expectancy ≥ 12 weeks.
• Subject must have adequate hematologic and organ function.
• Female subject of childbearing potential has a negative serum pregnancy test.
• Female subjects of childbearing potential and male subjects with partner of childbearing potential should agree to keep abstinence (refuse to heterosexual intercourse) or use one or more methods of contraception of which the failure rate is less than 1% per year starting with the first dose of study drug through at least 6 months after the last dose of study therapy.
• Histologic confirmation of advanced hepatocellular carcinoma, disease not eligible for curative surgical and/or locoregional therapies, OR progressive disease after surgical and /or locoregional therapies.
• At least one RECIST 1.1 measurable untreated lesion. All subjects must have at least one previously untreated, unidimensionally measurable lesion by contrast-enhanced spiral computed tomography (CT) ≥10 mm or contrast enhanced dynamic magnetic resonance imaging (MRI) scan ≥10 mm (malignant lymph nodes must be ≥15 mm on short axis).
• Subject is male or female ≥ 18 years and ≤ 75 years of age on the day of signing informed consent,and subject has voluntarily agreed to participate by giving written informed consent.
• Subject must have a performance status of 0 to 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
• Cirrhotic status of Child-Pugh Class A.
• Subjects are eligible to enroll if they have non-viral-HCC, or if they have HBV-HCC, or HCV-HCC defined as follows:
• i) HBV-HCC: Resolved HBV infection (as evidenced by detectable HBV surface antibody, detectable HBV core antibody, undetectable HBV DNA, and undetectable HBV surface antigen) or Chronic HBV infection (as evidenced by detectable HBV surface antigen or HBV DNA). Subjects with chronic HBV infection must have HBV DNA \< 104 copies/ml and must be on antiviral therapy.

You may not qualify if:

• Subject Is currently participating and receiving study therapy or has participated in a study of an investigational agent and receive study therapy within 28 days of the first dose of study drug.
• Subject has not recovered to CTCAE Grade 1 or better from the adverse events due to cancer therapeutics administered
• Subject has a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds (ms)), or a history of additional risk factors for torsade de pointes (TdP, e.g., heart failure, hypokalemia, family history of Long QT Syndrome), or is using concomitant medications that prolong the QT/QTc interval.
• Subject has had antineoplastic therapy within 4 weeks prior to the first dose of study therapy KN035.
• Subject is, with one year of the time signing informed consent, a regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol).
• Subjects with symptomatic ascites, pleural effusion or pericardial effusion.
• Subject is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study.
• Subject has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 4 weeks prior to study entry, have no evidence of new or enlarging brain metastases and are off steroids for at least 7 days from first dose of KN035.
• Subject has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Subject has Leptomeningeal disease.
• Subject previously had a severe hypersensitivity reaction to treatment with another mAb.
• Subject has an active infection (CTCAE≥Grade 2) with 4 weeks of the first dose.
• Subject is positive for Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), active hepatitis B (HBV surface antigen positive and HBV DNA ≥ 104 copies/ml)or hepatitis C or tuberculosis (HCV antibody positive and HCV-RNA≥ 103 copies/ml).
• Subject has received or will receive a live vaccine within 4 weeks prior to the first administration of study drug.
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.

Sponsors & Collaborators

• 3D Medicines (Sichuan) Co., Ltd.: lead

Study Sites (4)

Hunan Cancer Hospital

Changsha, Hunan, China

Location

First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China

Location

Zhongshan Hospital affiliated to Fudan University

Shanghai, Shanghai Municipality, China

Location

Affiliated Hospital of Military academy of medical sciences

Beijing, 100071, China

Location

Related Publications (1)

• Cui C, Wang J, Wang C, Xu T, Qin L, Xiao S, Gong J, Song L, Liu D. Model-informed drug development of envafolimab, a subcutaneously injectable PD-L1 antibody, in patients with advanced solid tumors. Oncologist. 2024 Sep 6;29(9):e1189-e1200. doi: 10.1093/oncolo/oyae102.

  PMID: 38982653 DERIVED

MeSH Terms

Interventions

envafolimab

Study Officials

• jianming xu

  Affiliated Hospital of Military academy of medical sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2017
• First Posted: April 5, 2017
• Study Start: March 21, 2017
• Primary Completion: September 2, 2019
• Study Completion: August 25, 2020
• Last Updated: March 3, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (4)