A Study of TQB2930 for Injection Monotherapy or Combination Therapy in Patients With Recurrent/Metastatic Breast Cancer

A Phase Ib/II Clinical Trial to Evaluate the Safety and Efficacy of TQB2930 for Injection Monotherapy or in Combination for the Treatment of Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Recurrent / Metastatic Breast Cancer

This is a phase Ib/II exploratory study. Phase Ib includes the dose escalation and expansion study of monotherapy, as well as the dose escalation study of combination therapy. After determining the maximum tolerated dose (MTD), a dose expansion study is conducted to observe the safety and efficacy in monotherapy. Phase II study is to further observe the safety and efficacy of TQB2930 combined with albumin-paclitaxel (cohort 3), or chemotherapy selected by investigators (cohort 4).

Study Overview

• Status: Recruiting
• Conditions: Metastatic Breast Cancer; Advanced Malignancies; Recurrent Breast Cancer
• Intervention / Treatment: Drug: TQB2930 for injection; Drug: Paclitaxel for injection (albumin-bound); Drug: TQB3616 capsule; Drug: Fulvestrant injection; Drug: Capecitabine tablets; Drug: Vinorelbine tartrate injection; Drug: Eribulin mesylate injection; Drug: gemcitabine hydrochloride for injection

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Qingyuan Zhang, Doctor; Phone Number: +86 0451 86298070; Email: sy86298276@163.com
• Study Contact Backup: Name: Xiaohua Zeng, Doctor; Phone Number: 13983687701; Email: zengxiaohua000017@163.com

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Affiliated Cancer Hospital of Chongqing University
      • Contact: Xiaohua Zeng; Phone Number: 13983687701; Email: zengxiaohua000017@163.com
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • Recruiting
      • Affiliated Cancer Hospital of Harbin Medical University
      • Contact: Qingyuan Zhang, Doctor; Phone Number: +86 0451 86298070; Email: sy86298276@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age: 18-75 years old; Eastern Cooperative Oncology Group Performance Status (ECOG PS) score: 0~1; The expected survival is over 3 months.

• Phase Ib

  1. Advanced malignancies confirmed by cytology / histopathology, priority given to subjects with HER2 expression or amplification;
  2. Subjects with malignant tumors who have failed standard treatment or lack effective treatment;
  3. Confirmed presence of at least one evaluable lesion according to RECIST 1.1 criteria

• Phase II

  1. Hormone receptor (HR)-negative, HER2-positive breast cancer confirmed by cytology / histopathology, with evidence of local recurrence or distant metastasis, unsuitable for surgery or radiotherapy for curative purposes:
  2. Have not received systemic antitumor therapy for metastatic stage; Systemic use of endocrine therapy is permitted, but not exceed 2 lines;
  3. at least one measurable lesion that meets the RECIST 1.1 criteria.
• Major organs are functioning normally.
• Female subjects of reproductive age should agree to use contraceptive methods during the study period and until 6 months after the end of the study; Negative serum pregnancy / urine pregnancy test within 7 days prior to study enrollment and must be non-lactating subjects; Male subjects should agree to use contraception during the study and until six months after the end of the study.

Exclusion Criteria:

• Have occured other malignant tumors within 3 years prior to first dose.
• Unalleviated toxicity above Common Terminology Criteria for Adverse Events (CTCAE) grade 1 due to any prior treatment;
• Received major surgical treatment, open biopsy, or significant traumatic injury within 28 days prior to the first dose;
• Long-term unhealed wounds or fractures;
• Arterial/venous thrombosis events occurred within 6 months before the first dose;
• Have a history of psychotropic drug abuse and can't get rid of it or have mental disorders;
• Subject with any severe and/or uncontrolled disease;
• Subjects who have been treated with other antitumor agents such as chemotherapy, radiotherapy, or immunotherapy within 4 weeks prior to the first dose, within 5 half-lives of the drug;
• Have used traditional chinese medicine with anti-tumor indications approved by National Medical Products Administration (NMPA) within 2 weeks before the first dose;
• Severe bone injury due to bone metastasis;
• Subjects with untreated active brain metastases or meningeal metastases or cancerous meningitis;
• In the course of previous HER2-targeted therapy, Left Ventricular Ejection Fractions (LVEF) decreased to <50% or absolute LVEF decreased >15%;
• Cumulative doses of anthracyclines exceeded doxorubicin or doxorubicin liposomes >360 mg/m2;
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requires continued bisphosphonate therapy
• Patients with severe hypersensitivity after the use of monoclonal antibodies;
• Has participated in other antitumor clinical trials within 4 weeks prior to the first dose.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TQB2930 for injection; TQB2930 for injection,10 mg/kg, quaque week (QW), 21 day as a treatment cycle; TQB2930 for injection, 20 mg/kg, quaque 2 weeks (Q2W), 28 day as a treatment cycle; TQB2930 for injection,30 mg/kg, quaque 3 weeks (Q3W), 21 day as a treatment cycle.	Drug: TQB2930 for injection; TQB2930 for injection is a HER2 bispecific antibody.
Experimental: TQB2930 for injection 30mg/kg + Paclitaxel for injection (albumin-bound); TQB2930 for injection 30mg/kg combined with paclitaxel (albumin-bound) for injection, 21 days for one treatment cycle	Drug: TQB2930 for injection; TQB2930 for injection is a HER2 bispecific antibody.; Drug: Paclitaxel for injection (albumin-bound); It is an anti-microtubule chemotherapy drug
Experimental: TQB2930 for injection+TQB3616 capsule for injection + fulvestrant injection; TQB2930 for injection 20mg/kg combined with TQB3616 capsule 120mg or 150mg or 180mg, and fulvestrant injection. Q2W, 28 days a cycle.	Drug: TQB2930 for injection; TQB2930 for injection is a HER2 bispecific antibody.; Drug: TQB3616 capsule; TQB3616 capsule is a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.; Drug: Fulvestrant injection; Fulvestrant is a competitive estrogen receptor antagonist with similar affinity to estradiol
Experimental: TQB2930 for injection + chemotherapy; TQB2930 for injection 30mg/kg combined with capecitabine tablets or vinorelbine tartrate injection or eribulin mesylate injection or gemcitabine hydrochloride for injection, 21 days a cycle.	Drug: TQB2930 for injection; TQB2930 for injection is a HER2 bispecific antibody.; Drug: Capecitabine tablets; Capecitabine is converted to 5-fluorouracil (5-FU) by in vivo enzyme action.; Drug: Vinorelbine tartrate injection; Vinorelbine is an anti-tumor drug of vinca alkaloids.; Drug: Eribulin mesylate injection; Eribulin induces G2/M phase cell cycle arrest, mitotic spindle division, and ultimately apoptosis after prolonged mitotic arrest through its tubulin-based anti-mitotic mechanism.; Drug: gemcitabine hydrochloride for injection; Gemcitabine is a cell cycle specific anti-metabolic anticancer agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	The highest dose when dose-limiting toxicity (DLT) occurs in less than 33% of subjects.	Baseline up to 4 months
Phase II recommended dose (P2RD)	Optimal tolerated dose determined after the end of phase 1	Baseline up to 1 year
Investigators assessed Objective remission rate (ORR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1	The proportion of subjects with complete response (CR) and partial response (PR) whose tumor volume reduced to a predetermined value and maintained the minimum time limit.	Baseline up to 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity	Incidence of anti-drug antibody (ADA)	Pre-dose on Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, Cycle 7 Day 1, Cycle 12 Day 1, each cycle is 21 or 28 days.
Peak concentration (Cmax), QW	The maximum serum concentration after administration	Pre-dose, 30 minuets, 4, 8, 24, 48, 72 hours after dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 8, each cycle is 21 days.
Peak concentration (Cmax), Q2W	The maximum serum concentration after administration	Pre-dose, 30 minuets, 4, 8, 24, 48, 72, 168, 240 hours after dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 1 Day 15, Cycle 2 Day 15, each cycle is 28 days.
Peak concentration (Cmax), Q3W	The maximum serum concentration after administration	Pre-dose, 30 minuets, 4, 8, 24, 48, 72, 168, 240, 336 hours after dose on Cycle 1 Day 1, Cycle 2 Day 1; Pre-dose on Cycle 3 Day 1, each cycle is 21 days.
Overall survival (OS)	From randomization to the time of death from any cause.	Baseline up to 4 years
Adverse event rate	The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs).	Baseline up to 2 years
Progression-free survival (PFS)	The time between the first medication and disease progression (PD) or death before PD.	Baseline up to 1 year
Disease control rate (DCR)	The ratio of disease control cases (partial remission, complete response, stable disease) to total cases.	Baseline up to 2 years
Duration of remission (DOR)	The time from the first evaluation of the tumor as a complete or partial response to the first evaluation as tumor progression or death.	Baseline up to 2 years
Clinical benefit rate (CBR)	The ratio of disease control cases (partial remission, complete response, stable disease ≥ 6 month) to total cases.	Baseline up to 2 years
Peak concentration (Cmax), arm 2	The maximum serum concentration after administration in arm 2	Pre-dose, 30 minuets after dose of Cycle 1 Day 1,Cycle 2 Day 1, Cycle 4 Day 1,Cycle 7 Day 1,Cycle 12 Day 1,Cycle 17 Day 1. each cycle is 28 days.
Peak concentration (Cmax), arm 3 and 4	The maximum serum concentration after administration in arm 3 and 4.	Pre-dose, 30 minuets after dose of Cycle 1 Day 1,Cycle 2 Day 1, Cycle 4 Day 1,Cycle 7 Day 1,Cycle 12 Day 1,Cycle 17 Day 1. each cycle is 21 days.

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): October 1, 2027

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: January 10, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Disease Attributes; Breast Diseases; Breast Neoplasms; Recurrence; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Paclitaxel; Capecitabine; Fulvestrant; Vinorelbine; Gemcitabine
• Other Study ID Numbers: TQB2930-Ib/II-01

Drug and device information, study documents

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