Clinical trial NCT04040699: KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor
Official title: A Phase Ib Study to Evaluate Efficacy, Safety and Tolerability of KN026 Combined With KN046 in Subjects With HER2 Positive Solid Tumor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HER2 Positive Solid Tumor
Keywords: KN026
KN046
HER2 Positive Solid Tumor
Lead sponsor: Peking University
Sponsor class: OTHER
Collaborators: name: Jiangsu Alphamab Biopharmaceuticals Co., Ltd
First posted: 2019-08-01
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity（DLT）
timeFrame: 28 days
measure: Objective response rate (ORR)
timeFrame: up to 2 years
measure: Duration of response (DOR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Clinical benefit rate
timeFrame: up to 2 years
measure: Progression free survival (PFS) rates
timeFrame: 6 months and 12 months
measure: Overall survival (OS) rates
timeFrame: 6 months and 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
affiliation: Peking University
name: Lin Shen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: