Study in Participants With Early-Stage or Locally Advanced Human Epidermal Growth Factor Receptor (HER) 2-Positive and Estrogen Receptor/Progesterone Receptor Negative Breast Cancer to Evaluate the Efficiency and Safety of Treatment With Trastuzumab Plus (+) QL1209/Pertuzumab + Docetaxel.

A Randomized, Multicenter, Double-Blind, Parallel-Controlled, Phase III Clinical Study to Evaluate QL1209/Pertuzumab in Combination With Docetaxel in Patients With Early-Stage or Locally Advanced HER2-Positive and ER/PR-negative Breast Cancer.

This is a randomized, double-blind, multicenter trial，parallel control designed to evaluate treatment with trastuzumab + QL1209 + docetaxel compared with trastuzumab + pertuzumab + docetaxel in the participants with early-stage or locally advanced HER2-positive and estrogen receptor/progesterone receptor negative breast cancer. The anticipated treatment duration is approximately 140 days.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab; Drug: QL1209; Drug: Docetaxel; Procedure: surgery; Drug: Pertuzumab

Detailed Description

This is A multi-center, randomized, double-blind, parallel control，comparative clinical trial.

The primary objective is to evaluate whether the clinical efficacy of QL1209 and pertuzumab are similar in patients with early-stage or locally advanced HER2-positive and estrogen receptor/progesterone receptor negative breast cancer.

The secondary objective are to evaluate whether the clinical safety and immunogenicity of QL1209 and pertuzumab are similar in patients with early-stage or locally advanced HER2-positive and estrogen receptor/progesterone receptor negative breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 517
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 2000 32
      • Fudan University Cancer Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300171
      • Tianjin Medical University Cancer Institution & Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Volunteer to participate in this clinical study; Completely understand and know this study as well as sign the informed consent form (ICF);
2. Age ≥ 18 years and ≤ 80 years when ICF is signed;
3. Histologically confirmed invasive breast carcinoma with a primary tumor size of more than (>) 2 centimeters (cm) by standard local assessment technique; Breast cancer stage at presentation: early-stage (T2-3, N0-1, M0) or locally advanced (T2-3, N2 or N3, M0; T4, any N, M0); HER2-positive breast cancer confirmed by immunohistochemistry or HER2 gene amplification by in situ hybridization; Estrogen receptor and Progesterone receptor negative.
4. Eastern Cooperative Oncology Group Performance Status equal to or less than (<=) 1.
5. Baseline left ventricular ejection fracture >= 55% measured by echocardiography (preferred) or multiple gated acquisition scan

Exclusion Criteria:

1. Stage IV metastatic breast cancer;
2. Inflammatory breast cancer;
3. Previous anti-cancer therapy or radiotherapy for any malignancy;
4. History of malignancies other than colorectal cancer within 5 years prior to randomization, excluding cutaneous basal cell carcinoma, cervical carcinoma in situ, and thyroid papillary adenocarcinoma of non-melanoma after radical treatment;
5. Concurrent anti-cancer treatment in another investigational trial, including hormone therapy, bisphosphonate therapy, or immunotherapy;
6. Major surgical procedure within 4 weeks prior to randomization or from which the participant has not fully recovered;
7. Serious cardiac illness or medical condition;
8. Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness;
9. Sensitivity to any of the study medications, any of the ingredients or excipients of these medications, or benzyl alcohol;
10. Pregnant or lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab Plus（+） QL1209 + Docetaxel; Prior to surgery: trastuzumab, QL1209, and docetaxel for 4 cycles (1 cycle = 21 days) Drug: Docetaxel Drug: QL1209 Drug: Trastuzumab Procedure: Surgery	Drug: Trastuzumab; Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4.; Other Names: Herceptin®; Drug: QL1209; QL1209 IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4.; Other Names: Recombinant anti-HER-2 domain Ⅱ humanized monoclonal antibody injection; Drug: Docetaxel; Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4; Other Names: Docetaxel injection; Procedure: surgery; All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.
Active Comparator: Trastuzumab Plus（+） Pertuzumab + Docetaxel; Prior to surgery: trastuzumab,pertuzumab , and docetaxel for 4 cycles (1 cycle = 21 days) Drug: Docetaxel Drug: Pertuzumab Drug: Trastuzumab Procedure: Surgery	Drug: Trastuzumab; Trastuzumab IV infusion in 3-week cycles. Neoadjuvant treatment: 8 milligrams per kilogram (mg/kg) loading dose for Cycle 1, followed by 6 mg/kg for Cycles 2-4.; Other Names: Herceptin®; Drug: Docetaxel; Docetaxel IV infusion in 3-week cycles. Neoadjuvant treatment: 75 mg/m2 for Cycles 1-4; Other Names: Docetaxel injection; Procedure: surgery; All participants who are eligible for surgery will undergo surgery and have their pathologic response evaluated.; Drug: Pertuzumab; Pertuzumab IV infusion in 3-week cycles. Prior to surgery (neoadjuvant treatment): 840 milligrams (mg) loading dose for Cycle 1, followed by 420 mg for Cycles 2-4.; Other Names: Perjeta®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total pathologic complete response (tpCR) rate	Total pathologic complete response (tpCR) rate, defined as ypT0/is, ypN0 as assessed by an Independent Review Committee (IRC)	Approximately 26 months after randomization of the first patient, when all patients have completed the treatment completion/discontinuation visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With tpCR as Assessed by the Local Pathologist	This tpCR was assessed by the local pathologist. tpCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system).	At surgery
Percentage of Participants With Breast Pathologic Complete Response (bpCR) assessed by the IRC	This bpCR was assessed by the IRC. bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system).	Approximately 26 months after randomization of the first patient, when all patients have completed the treatment completion/discontinuation visit
Percentage of Participants With bpCR as Assessed by the Local Pathologist	This bpCR was assessed by the local pathologist. bpCR is defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is in accordance with current AJCC staging system).	At surgery
Percentage of Participants With an Objective Response	An objective response was defined as the percentage of participants who achieved a complete response or partial response as the best tumor response during the neoadjuvant period (that is, during Cycles 1-4 prior to surgery), as determined by the investigator on the basis of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. No confirmation was required for objective response. Only participants with measurable disease at baseline were included in the analysis. The duration of one treatment cycle is 21 days; the administration of therapy in Cycle 5 should not occur until 2 weeks after surgery.	Before surgery

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jin Zhang, Professor, Tianjin Medical University Cancer Institute & Hospital; Principal Investigator: Zhimin Shao, Professor, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): November 23, 2020
• Primary Completion (Actual): August 22, 2022
• Study Completion (Actual): October 24, 2023

Study Registration Dates

• First Submitted: October 28, 2020
• First Submitted That Met QC Criteria: November 10, 2020
• First Posted (Actual): November 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Trastuzumab; Pertuzumab
• Other Study ID Numbers: QL1209-301

Drug and device information, study documents

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