Metastatic Breast Cancer, Recurrent Breast Cancer, Advanced Malignancies
Conditions
Brief summary
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).
Interventions
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.
DRUGgemcitabine hydrochloride for injection
Gemcitabine is a cell cycle specific anti-metabolic anticancer agent
DRUGTQB2930 for injection
TQB2930 for injection is a HER2 bispecific antibody.
It is an anti-microtubule chemotherapy drug
DRUGTQB3616 capsule
TQB3616 capsule is a Cyclin-dependent kinase 4/6 (CDK4/6) inhibitor.
Fulvestrant is a competitive estrogen receptor antagonist with similar affinity to estradiol
DRUGCapecitabine tablets
Capecitabine is converted to 5-fluorouracil (5-FU) by in vivo enzyme action.
Vinorelbine is an anti-tumor drug of vinca alkaloids.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose (MTD) | Baseline up to 4 months | The highest dose when dose-limiting toxicity (DLT) occurs in less than 33% of subjects. |
| Phase II recommended dose (P2RD) | Baseline up to 1 year | Optimal tolerated dose determined after the end of phase 1 |
| Investigators assessed Objective remission rate (ORR) based on Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 | Baseline up to 2 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax), Q3W | 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. | The maximum serum concentration after administration |
| Overall survival (OS) | Baseline up to 4 years | From randomization to the time of death from any cause. |
| Adverse event rate | Baseline up to 2 years | The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs). |
| Progression-free survival (PFS) | Baseline up to 1 year | The time between the first medication and disease progression (PD) or death before PD. |
| Immunogenicity | 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. | Incidence of anti-drug antibody (ADA) |
| Duration of remission (DOR) | Baseline up to 2 years | The time from the first evaluation of the tumor as a complete or partial response to the first evaluation as tumor progression or death. |
| Clinical benefit rate (CBR) | Baseline up to 2 years | The ratio of disease control cases (partial remission, complete response, stable disease ≥ 6 month) to total cases. |
| Peak concentration (Cmax), 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. | The maximum serum concentration after administration in arm 2 |
| Peak concentration (Cmax), 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. | The maximum serum concentration after administration in arm 3 and 4. |
| Disease control rate (DCR) | Baseline up to 2 years | The ratio of disease control cases (partial remission, complete response, stable disease) to total cases. |
| Peak concentration (Cmax), QW | 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. | The maximum serum concentration after administration |
| Peak concentration (Cmax), Q2W | 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. | The maximum serum concentration after administration |
Countries
China
Contacts
Primary ContactQingyuan Zhang, Doctor
Backup ContactXiaohua Zeng, Doctor
Outcome results
None listed