Advanced Solid TumorsPhase 1NCT03897283
Study of TQB2450 Combined With Anlotinib in Patients With Advanced Solid Tumors
A Phase 1 study testing TQB2450 and Anlotinib in people with Advanced Solid Tumors, run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- TQB2450 and Anlotinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteChina
- Study dates
- 20 Jun 2019to Dec 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically or cytologically confirmed advanced or metastatic solid tumor that is failure or absence of standard therapy with measurable lesion.
- 18-70 years old；Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
- The main organs function are normally, the following criteria are met:
- ① routine blood tests：hemoglobin (Hb) ≥ 90g/L (no blood transfusion and blood products within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT) ≥ 100×109/L;
- ②Blood biochemical examination: alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (when the liver is invaded，AST ≤ 5×ULN); total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome patients，TBIL ≤ 3×ULN)；serum creatinine (Cr) ≤1.5×ULN，or calculated creatinine clearance (CrCl) ≥60 ml/min；
- ③Coagulation function: activated partial thromboplastin time (APTT) 、 international normalized ratio (INR) 、prothrombin time (PT) ≤1.5×ULN；
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- ④ left ventricular ejection fraction (LVEF) measured by the Cardiac echocardiography ≥ 50%.
- 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
- Understood and signed an informed consent form.
Who cannot join
- Prior therapy with anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other immunotherapy against PD-1/PD-L1.
- Severe hypersensitivity occurs after administration of other monoclonal antibodies.
- Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include cured basal cell carcinoma of skin and carcinoma in situ of cervix.
- 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.
- 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.
- 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 uncontrollable pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.
- Has spinal cord compression which was not cured or relieved through surgery and/or radiotherapy, or diagnosed spinal cord compression after treatment showed no clinical evidence of disease stabilization prior to randomization ≥1 week.
- Has any bleeding or bleeding events ≥ grade 3 or with unhealed wounds, ulcerative , or fractures within 4 weeks prior to the first administration.
- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis. （subjects with treated brain metastases may participate provided the following criteria are met： Has no evidence of new or enlarging brain metastases at least two weeks after treatment of brain metastases ； Has stopped using corticosteroid before randomization, or used less than 10 mg prednisone or steady dose at least two weeks；If the patient is found to have active or new untreated or asymptomatic CNS metastases during the screening period, radiotherapy and/or operation for CNS metastatic lesion must be performed.
- Has received chemotherapy, surgery, radiotherapy, the last treatment from the first dose less than 4 weeks, or oral targeted drugs for less than 5 half-lives, or oral fluorouracil pyridine drugs for less than 14 days, mitomycin C and nitrosourea for less than 6 weeks.
- Has adverse events caused by previous therapy except alopecia that did not recover to ≤ grade 1.
- Has major surgical procedure、biopsy or obvious traumatic injury within 28 days before randomization.
- Has arterial or venous thromboembolic events occurred within 6 months, such as cerebrovascular accident including transient ischemic attack, deep vein thrombosis and pulmonary embolism.
- Has drug abuse history that unable to abstain from or mental disorders.
- Patients with any serious and/or uncontrollable disease, including :
- Has poor blood pressure control, systolic blood pressure ≥ 150 mmHg, diastolic blood pressure ≥ 90 mmHg;
- Thrombotic events, ischemic attacks, myocardial infarction, grade 2 congestive heart failure or arrhythmias requiring treatment including QTc ≥ 480ms occurred within 6 months of first administration;
- Severe active or uncontrolled infections ≥ grade 2;
- Has known clinical history of liver diseases, including viral hepatitis, known carriers of hepatitis B virus (HBV) must exclude active HBV infection, that is, HBV DNA positive > 1 *104 copies/mL or > 2000 IU/mL, known hepatitis C virus infection (HCV) and HCV RNA positive > 1 *103 copies/mL, or other decompensated hepatitis and chronic hepatitis, which require antiviral treatment;
- HIV positive;
- Poor control of diabetes mellitus, fasting blood-glucose ≥ grade 2;
- Urinary routine indicated that urinary protein ≥ ++ and confirmed 24-hour urinary protein quantification > 1.0 g.
- Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration.
- Has participated in other anticancer drug clinical trials within 4 weeks.
- According to the judgement of the researchers, there are other factors that may lead to the termination of the study. For example, other serious diseases including mental disorders need to be treated together, serious laboratory abnormalities, accompanied by family or social factors, which will affect the safety of the subjects, or the collection of data and samples.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Jilin Cancer Hospital
Changchun, Jilin
Ying Cheng, Doctor, 0431-85873390, jl.cheng@163.com
Ying Cheng, Doctor
About this study
Official title: Phase Ib Study of TQB2450 Combined With Anlotinib in Patients With Advanced Solid Tumors
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. As a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling，anlotinib is approved for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have undergone progression or recurrence after ≥ 2 lines of systemic chemotherapy. The Phase III study showed that the Overall Survival (OS), Progression-Free Survival (PFS) and Overall Response Rate (ORR) were significantly better than placebo group.
- Conditions
- Advanced Solid Tumors
- Being tested
- TQB2450, Anlotinib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TQB2450Drug
TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle
AnlotinibDrug
Anlotinib capsules given orally in fasting conditions, dose ranging from 8 mg to 12 mg once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). Initial dose is 10 mg. If there are no patients with DLT in first treatment cycle , begin to explore dose of 12 mg. If there are 2 or more patients in 3 patients with DLT, 8 mg dose is to explore.
| Study group | Role | What they receive |
|---|---|---|
| Anlotinib + TQB2450 | Experimental | TQB2450 1200 milligrams (mg) administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 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) Receives: Drug: TQB2450; Drug: Anlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
DLT defined as any of the following events occurring during the study related to drugs : （1） ≥grade 3 non-hematologic toxicity, except for the following conditions: Nausea, vomiting, diarrhea, constipation, electrolyte imbalance that downgrade within 1 week after supportive treatment； Grade 3 fatigue ≤ 7 days duration； Grade 3 hypertension that can be controlled within 1 week by medication； Alopecia, fever caused by tumor or infection, and elevated alkaline phosphatase; （2）Grade 4 neutropenia, thrombocytopenia, and hemoglobin reduction confirmed by at least 2 tests within 2 days; Grade 3 thrombocytopenia with bleeding tendency confirmed by at least 2 tests within 2 days; （3）Grade 3 neutropenia with fever confirmed at least 2 times within 2 days (neutrophil count <1.0×109 / L; fever ≥38.5℃) （4）Immune-related interstitial pneumonia ≥ grade 2 ； （5）Decreased ventricular ejection fraction ≥ grade 2 ； （6）Retinal vein occlusion (RVO), uveitis ≥ grade 2 , and other more serious ocular
Measured: Baseline up to 21 days
Maximum tolerated dose (MTD)
MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT)
Measured: Baseline up to 21 days
Determine the Recommended Phase II Dose (RP2D)
The RP2D defined as the lower dose level to MTD based on the safety profile
Measured: Up to approximately 18 months
Secondary outcomes (5)
Overall response rate (ORR)
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR)
Measured: Up to approximately 18 months
Disease control rate (DCR)
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) and Stable Disease (SD)
Measured: Up to approximately 18 months
Progression-free survival (PFS)
PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause
Measured: Up to approximately 18 months
Overall survival (OS)
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
Measured: Up to approximately 24 months
Adverse Event: Drug dose adjustment
Security Index
Measured: up to approximately 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2019
- Study start20 Jun 2019
- Primary completion30 Jun 2020 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03897283
- Sponsor's protocol ID
- TQB2450-Ib-04
- Status last verified
- Mar 2019
- First submitted
- 27 Mar 2019
- Last updated
- 30 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of TQB2450 Combined With Anlotinib in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT03897283
- Acronym / sponsor ID
- TQB2450-Ib-04
- Conditions
- Advanced Solid Tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Chia Tai Tianqing Pharmaceutical Group Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 20 Jun 2019 (actual)
- Primary completion
- 30 Jun 2020 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 1 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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. As a novel multitarget tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling，anlotinib is approved for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have undergone progression or recurrence after ≥ 2 lines of systemic chemotherapy. The Phase III study showed that the Overall Survival (OS), Progression-Free Survival (PFS) and Overall Response Rate (ORR) were significantly better than placebo group.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Anlotinib + TQB2450 | Experimental | Drug: TQB2450, Drug: AnlotinibTQB2450 1200 milligrams (mg) administered intravenously (IV) on Day 1 of each 21-day cycle plus Anlotinib capsules 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) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically or cytologically confirmed advanced or metastatic solid tumor that is failure or absence of standard therapy with measurable lesion.
- 18-70 years old；Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months.
- The main organs function are normally, the following criteria are met:
- ① routine blood tests：hemoglobin (Hb) ≥ 90g/L (no blood transfusion and blood products within 14 days); absolute neutrophil count (ANC) ≥1.5×109/L; platelets (PLT) ≥ 100×109/L;
- ②Blood biochemical examination: alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN (when the liver is invaded，AST ≤ 5×ULN); total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome patients，TBIL ≤ 3×ULN)；serum creatinine (Cr) ≤1.5×ULN，or calculated creatinine clearance (CrCl) ≥60 ml/min；
Key exclusion criteria (26 listed)
- Prior therapy with anlotinib, anti-programmed cell death (PD)-1, anti-PD-L1 or other immunotherapy against PD-1/PD-L1.
- Severe hypersensitivity occurs after administration of other monoclonal antibodies.
- Has diagnosed and/or treated additional malignancy within 5 years prior to randomization. Exceptions include cured basal cell carcinoma of skin and carcinoma in situ of cervix.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TQB2450TQB2450 1200 mg administered IV on Day 1 of each 21-day cycle | Drug | Anlotinib + TQB2450 |
| AnlotinibAnlotinib capsules given orally in fasting conditions, dose ranging from 8 mg to 12 mg once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21). Initial dose is 10 mg. If there are no patients with DLT in first treatment cycle , begin to explore dose of 12 mg. If there are 2 or more patients in 3 patients with DLT, 8 mg dose is to explore. | Drug | Anlotinib + TQB2450 |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: Baseline up to 21 days
DLT defined as any of the following events occurring during the study related to drugs : （1） ≥grade 3 non-hematologic toxicity, except for the following conditions: Nausea, vomiting, diarrhea, constipation, electrolyte imbalance that downgrade within 1 week after supportive treatment； Grade 3 fatigue ≤ 7 days duration； Grade 3 hypertension that can be controlled within 1 week by medication； Alopecia, fever caused by tumor or infection, and elevated alkaline phosphatase; （2）Grade 4 neutropenia, thrombocytopenia, and hemoglobin reduction confirmed by at least 2 tests within 2 days; Grade 3 thrombocytopenia with bleeding tendency confirmed by at least 2 tests within 2 days; （3）Grade 3 neutropenia with fever confirmed at least 2 times within 2 days (neutrophil count <1.0×109 / L; fever ≥38.5℃) （4）Immune-related interstitial pneumonia ≥ grade 2 ； （5）Decreased ventricular ejection fraction ≥ grade 2 ； （6）Retinal vein occlusion (RVO), uveitis ≥ grade 2 , and other more serious ocular
Maximum tolerated dose (MTD)
Time frame: Baseline up to 21 days
MTD defined as the highest dose level at which less than or equal to 2 of 6 subjects experience dose limiting toxicity (DLT)
Determine the Recommended Phase II Dose (RP2D)
Time frame: Up to approximately 18 months
The RP2D defined as the lower dose level to MTD based on the safety profile
5 secondary outcomes
Overall response rate (ORR)
Time frame: Up to approximately 18 months
Disease control rate (DCR)
Time frame: Up to approximately 18 months
Progression-free survival (PFS)
Time frame: Up to approximately 18 months
Overall survival (OS)
Time frame: Up to approximately 24 months
Adverse Event: Drug dose adjustment
Time frame: up to approximately 18 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TQB2450 and Anlotinib in people with Advanced Solid Tumors, run by Chia Tai Tianqing Pharmaceutical Group Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 30 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact ying cheng, doctor (0431-85873390, jl.cheng@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: Baseline up to 21 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Oct 2019.