KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor

Phase 1

Completed

• Conditions: HER2 Positive Solid Tumor
• Interventions: Biological: KN026 combined with KN046

• Registration Number: NCT04040699
• Lead Sponsor: Peking University

Brief Summary

This is a phase Ib, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of KN026 combined with KN046 in subjects with advanced HER2 positive solid tumors.

Detailed Description

The study is composed of 2 stages. Stage 1 consists of dose escalation cohorts for determining the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 consists of 4 tumor type expansion cohorts for expanding the information on clinical safety, clinical pharmacokinetics and antitumor activity in HER2 positive patients.

Study Timeline

• Study First Submitted: 2019-07-30
• Study First Submitted QC: 2019-07-30
• Study First Posted: 2019-08-01
• Study Start: 2019-09-26
• Primary Completion: 2022-09-22
• Study Completion: 2023-12-01
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-06
• Last Update Posted: 2024-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

• Signed inform consent form (ICF)
• Age ≥ 18 years and ≤ 75 years, male or female
• Histologically or cytologically documented advanced HER2 positive solid tumor
• Received at least one prior standard therapy
• At least one measurable lesion according to Response Evaluation Criteria In Solid Tumors（RECISIT） v 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ function
• LVEF≥ 50% (ECHO)
• Female patients and males with partners of childbearing potential should be using highly effective contraceptive measures (failure rate of less than 1% per year). Contraception should be continued for a period of 24 weeks after dosing has been completed.
• Ability to comply with treatment, procedures and pharmacokinetics (PK) sample collection and the required study follow-up procedures

Exclusion Criteria

• Accepted any other anti-tumor drug therapies within 4 weeks before fist dose
• Accepted radiotherapy within 4 weeks before enrollment
• An anthracyclines antibiotic treatment was received exceeding 320 mg/m² or other equivalent dose antharcyclines
• Subjects are eligible with clinically controlled and stable neurologic function >= 4 weeks, which is no evidence of CNS disease progression; Subjects with spinal cord compression and cancerous meningitis are not eligible
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment (with the exception of subjects with adrenal insufficiency, who may continue corticosteroids at physiologic replacement doses, equivalent to < 10 mg prednisone daily, inhaled steroids and topical use of steroids)
• Vaccination within 28 days of the first administration of trial treatment, except for administration of inactivated vaccines (e.g., inactivated influenza vaccines)
• Pregnant or nursing females；or intend pregnancy within this study period or within 6 monthes after the end of this study
• Severe chronic and active infection, need to system antibiosis/antiviral treatment
• Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management
• Cavity effusion (pleural effusion, ascites, pericardial effusion, etc.) are not well controlled, and need locally treatment or repeated drainage

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KN026 combined with KN046	KN026 combined with KN046	KN026 is an anti-HER2 bispecific antibody that can simultaneously bind two non-overlapping epitopes of HER2, leading to a dual HER2 signal blockade. KN046 is a PD-L1 - CTLA-4 bispecific antibody.

Primary Outcome Measures

Name	Time	Method
Duration of response (DOR)	up to 2 years	Duration of response (DOR) per RECIST 1.1 criteria according to investigators assessment
Dose-limiting toxicity（DLT）	28 days	Dose-limiting toxicity
Objective response rate (ORR)	up to 2 years	Objective response rate (ORR) per RECIST 1.1 criteria according to investigators assessment

Secondary Outcome Measures

Name	Time	Method
Progression free survival (PFS) rates	6 months and 12 months	Progression free survival (PFS) rates
Clinical benefit rate	up to 2 years	Clinical benefit rate
Overall survival (OS) rates	6 months and 12 months	Overall survival (OS) rates

Trial Locations

Locations (1)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China