Study of TQB2450 Combined With Anlotinib in the Treatment of Mutation Positive Lung Cancer
Study Details
Study Description
Brief Summary
This is an open-label, single center, non-randomized, phase Ib trial to evaluate safety and efficacy of TQB2450 injection combined with anlotinib in patients with advanced mutation positive non-small cell lung cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: TQB2450 Combined with Anlotinib TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 12 mg given orally in fasting conditions, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21) |
Drug: TQB2450
TQB2450 is a humanized monoclonal antibody targeting programmed death ligand-1 (PD-L1), which prevents PD-L1 from binding to PD-1 and B7.1 receptors on T cell surface, restores T cell activity, thus enhancing immune response and has potential to treat various types of tumors.
Drug: Anlotinib
a multi-target receptor tyrosine kinase inhibitor
|
Outcome Measures
Primary Outcome Measures
- Overall response rate （ORR） [up to approximately 12 months]
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR)
Secondary Outcome Measures
- Progression-free survival (PFS) [up to approximately 12 months]
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
- Overall survival (OS) [up to approximately 15 months]
OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.
- Disease control rate（DCR） [up to approximately 12 months]
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Understood and signed an informed consent form.
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18 years and older.
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Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, life expectancy≥ 12 weeks.
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Histologically or cytologically confirmed mutation positive non-small cell lung cancer according to 8th International Association for the Study of Lung Cancer (IASLC) edition.
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Has measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
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Adequate organ system function, defined as follows:
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absolute neutrophil count (ANC) ≥ 1.5×109/L, platelets (PLT) ≥ 100×109/L, hemoglobin (Hb)≥ 90g /L;
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total bilirubin (TBIL) ≤ 1.5×ULN；alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN (without liver metastasis) or ≤ 5.0 × ULN (with liver metastasis), Creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 50 ml/min;
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Urine protein < ++，or urine protein ≥ ++ concomitant with content of 24-hour urinary protein <1.0 g;
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international normalized ratio (INR) ≤ 1.5×ULN, activated partial thromboplastin time (APTT) ≤ 1.5×ULN;
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left ventricular ejection fraction (LVEF) ≥ 50%;
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Male or female subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 6 months after the last dose of study (such as intrauterine devices , contraceptives or condoms) ; No pregnant or breastfeeding women, and a negative pregnancy test are received within 7 days before the randomization.
Exclusion Criteria:
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Has diagnosed and/or treated additional malignancy within 5 years prior to randomization except of cured in situ carcinoma of the cervix, non-melanoma skin cancer and superficial bladder carcinoma.
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Has severe hypersensitivity reactions after taking other monoclonal antibodies.
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Has hypersensitivity reactions after taking anlotinib.
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Has prior therapy with anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other immunotherapy against PD-1/PD-L1.
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Has any active autoimmune disease or history of autoimmune disease, such as autoimmune hepatitis, interstitial pneumonia, enteritis, vasculitis, nephritis, asthma patients who need bronchiectasis for medical intervention; Subjects with the vitiligo without systemic treatment, psoriasis, alopecia, well-controlled type I diabetes mellitus, hypothyroidism stable on hormone replacement will not be excluded from this study.
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Has multiple factors affecting oral medication, such as inability to swallow, post-gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.
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Has clinical significance of thyroid dysfunctions within 6 months prior to enrollment, and even though medical therapy, thyroid function can not return to normal or no clinical significance.
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Has central nervous system (CNS) metastases without local therapy of lesion.
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Radiograph (within 28 days before enrollment) showed that the tumor surrounded important blood vessels, and the investigators determined that entering the study would cause bleeding risk.
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Hemoptysis (defined as coughing out or spitting out ≥ 1 teaspoon of blood or small blood clots or hemoptysis without sputum) within 28 days before enrollment , not including bloody sputum.
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Immunosuppressive therapy with immunosuppressive agents or systemic or absorbable local hormones (dosage > 10 mg/day prednisone or other therapeutic hormones) is required for the purpose of immunosuppression, and is still in use for 2 weeks after the first administration.
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Has any of the following severe acute complications:
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Unstable angina and/or congestive heart failure or vascular disease requiring hospitalization within 12 months, or other cardiac impairments determined by the investigator, which may affect the evaluation of drug safety; Myocardial infarction or ischemia with ST elevation ≥ 2 mm indicated by electrocardiogram (ECG);
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Has pulmonary infections and/or acute bacterial or fungal infections requiring intravenous antibiotic therapy;
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Has clinical jaundice caused by liver dysfunction;
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Virological test indicates one of the following items before enrollment:
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HBsAg positive and HBV DNA ≥ 1 × 10^3 copies/mL;
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Anti-HCV positive and HCV virus titer detection value exceeds the upper limit of normal value;
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HIV positive;
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Has participation in an anti-tumor clinical trial within 28 days prior to the first administration.
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Has serious affecting safety or treatment compliance concomitant diseases, according to the investigator's judgment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sun Yat-sen University Cancer Center | Guangzhou | Guangdong | China | 510060 |
Sponsors and Collaborators
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TQB2450-Ib-11