KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor

A Phase Ib Study to Evaluate Efficacy, Safety and Tolerability of KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor

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.

Study Overview

• Status: Completed
• Conditions: HER2 Positive Solid Tumor
• Intervention / Treatment: Biological: KN026 combined with KN046

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 Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: KN026 combined with KN046; KN026 and KN046 are given at 20mg/Kg and 3mg/Kg intravenously on day 1of each 2 weeks cycle at the beginning respectively.The dosage will be escalated if adverse events are tolerated according to the scheme.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) rates	Progression free survival (PFS) rates	6 months and 12 months
Overall survival (OS) rates	Overall survival (OS) rates	6 months and 12 months
Clinical benefit rate	Clinical benefit rate	up to 2 years

Collaborators and Investigators

• Sponsor: Peking University
• Collaborators: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
• Investigators: Principal Investigator: Lin Shen, MD,PhD, Peking University

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2019
• Primary Completion (Actual): September 22, 2022
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: July 30, 2019
• First Submitted That Met QC Criteria: July 30, 2019
• First Posted (Actual): August 1, 2019

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: KN026; KN046; HER2 Positive Solid Tumor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: KN046-IST-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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