A Study of KN046 in Subjects With Locally Advanced or Metastatic Triple-negative Breast Cancer

A Phase Ib/II Study to Evaluate Efficacy, Safety and Tolerability of KN046 Monotherapy or in Combination With Nab-paclitaxel in Subjects With Triple-negative Breast Cancer

This is an open-label, phase Ib/II, multi-center study to evaluate efficacy and safety of KN046 alone or in combination with nab-paclitaxel in subjects with locally advanced unresectable or metastatic triple negative breast cancer (TNBC). The study is composed of dose escalation and expansion parts. Every subject will subject tumor tissue used for biomarker evaluation. Each subject will receive KN046 or in combination with nab-paclitaxel untill confirmed progressive disease, unacceptable toxicity or withdrawal of informed consent whichever occurs first.

Study Overview

• Status: Completed
• Conditions: Triple-negative Breast Cancer
• Intervention / Treatment: Biological: KN046; Drug: Nab-paclitaxel

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
  • Fujian
    • Xiamen, Fujian, China
      • The first affiliated hospital of xiamen university
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin medical university cancer hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangsu
    • Nantong, Jiangsu, China
      • Nantong Tumor Hospital
  • Jilin
    • Changchun, Jilin, China
      • Jilin Cancer Hospital
  • Liaoning
    • Shenyang, Liaoning, China
      • Liaoning Cancer Hospital
  • Shandong
    • Liaocheng, Shandong, China
      • Liaocheng People's Hospital
    • Zibo, Shandong, China
      • Zibo Municipal Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed informed consent;
• Age of 18 or above;
• Histology confirmed locally advanced unresectable or metastatic triple-negative breaset cancer;
• (KN046 monotherapy) failed at least one prior anthracycline and taxane containing systemic treatment, (KN046 plus nab-paclitaxel) systemic treatment naive;
• Measurable disease at baseline;
• ECOG 0-1;
• Adequate organ functions.

Exclusion Criteria:

• Untreated active CNS metastasis or leptomeningeal metastasis;
• Subjects receiving immunosuppressive agents (such as steroids) for any reason should be tapered off these drugs before initiation of trial treatment;
• Has interstitial lung disease, or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management;
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent; History of uncontrolled intercurrent illness; Known severe hypersensitivity reactions to antibody drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: KN046; Subjects will receive KN046 at a dose of 3 mg/kg or 5 mg/kg via intravenous infusion on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity or completion of 2 years of treatment	Biological: KN046; KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle
Experimental: KN046 plus nab-paclitaxel; Subjects will receive KN046 at a dose of 3 mg/kg or 5 mg/kg via intravenous infusion on Days 1 and 15 of every 28-day cycle until disease progression, unacceptable toxicity or completion of 2 years of treatment Subjects will receive nab-paclitaxel at a dose of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of every 28-day cycle until disease progression or unacceptable toxicity	Biological: KN046; KN046 at a dose level of 3 or 5 mg/kg via intravenous infusion on Days 1 and 15 of 28-day cycle; Drug: Nab-paclitaxel; Nab-paclitaxel at dose level of 100 mg/m2 via intravenous infusion on Days 1, 8 and 15 of 28-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IRC assessed objective response	Objective response is defined as complete response (CR) or partial response (PR), as determined by the independent review committee using RECIST v1.1 criteria. CR is defined as the disappearance of all TLs and SA reduction to less than (<) 10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD	From Day 1 to PD, assessed up to 12 months after last patient last dose
IRC assessed duration of response	Duration of response is defined as the time period from the date of initial independent review committee assessed CR or PR until the date of PD or death from any cause, whichever occurs first. CR is defined as the disappearance of all TLs and SA reduction to <10mm for nodal TLs/ non-TLs. PR is defined as >/=30% decrease in SD of TLs, taking as reference the baseline SD. PD is defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions	From Day 1 to PD, assessed up to 12 months after last patient last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS rate at 6 and 12 months	PFS is defined as the time from Day 1 to the first occurrence of PD, as determined by the independent review committee or investigator using RECIST v1.1, or death from any cause during the study, whichever occurs first. PD is defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 millimeter (mm) of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. PFS rate at 6 and 12 months is defined as percentage of subjects who are alive without progressive disease or death at 6 and 12 months	From Day 1 to disease progression (PD) or death from any cause, assessed up to 12 months after last patient last dose
Frequency and severity of treatment emergent adverse events	Treatment emergent adverse event is defined as those events with onset days occurring during the on-treatment period till 90 days after last dose of KN046 or if the worsening of an event is during the on-treatment period till 90 days after last dose of KN046	From Day 1 to 90 days after last dose of KN046, through study completion, an average of 1 year
Percentage of subjects with anti-drug antibodies	ADA is defined as human anti-drug antibodies	Day 1 (pre-dose) to 90 days after last dose of KN046, through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Jiangsu Alphamab Biopharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start (Actual): May 30, 2019
• Primary Completion (Actual): August 16, 2022
• Study Completion (Actual): October 27, 2022

Study Registration Dates

• First Submitted: March 7, 2019
• First Submitted That Met QC Criteria: March 12, 2019
• First Posted (Actual): March 13, 2019

Study Record Updates

• Last Update Posted (Actual): June 8, 2023
• Last Update Submitted That Met QC Criteria: June 7, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: KN046-203

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all IPD that underlie results in a publication
• IPD Sharing Time Frame: 6 months after publication
• IPD Sharing Access Criteria: Health care professionals or researches may raise request to Sponsor to have access to study report, sub-group analysis
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

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