Efficacy and Safety Study of Anlotinib With Pembrolizumab in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Non-small Cell Lung Cancer
Efficacy and Safety Study of Anlotinib With Pembrolizumab in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Non-small Cell Lung Cancer
Sponsors
Source
Peking Union Medical College Hospital
Oversight Info
Has Dmc
No
Is Fda Regulated Drug
No
Is Fda Regulated Device
No
Brief Summary
The purpose of this study is to assess the safety and efficacy of Anlotinib (AL3818) combined
with pembrolizumab (MK-3475) in treatment-naïve adults with no prior systemic therapy for
advanced non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand
1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.
The primary study hypotheses is that the combination of Anlotinib and pembrolizumab is
superior to pembrolizumab alone(historical data) as assessed by Progression-free Survival
(PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).
Overall Status
Recruiting
Start Date
2019-11-16
Completion Date
2022-11-16
Primary Completion Date
2021-11-16
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
Progression-free Survival (PFS) as assessed by RECIST 1.1 |
Up to approximately 24 months |
Secondary Outcome
Measure |
Time Frame |
Objective Response Rate (ORR) as assessed by RECIST 1.1 |
Up to approximately 24 months |
Disease Control Rate (DCR) as assessed by RECIST 1.1 |
Up to approximately 24 months |
Overall Survival (OS) |
Up to 12 months after last patient last visit |
Progression Free Survival 2 (PFS2) |
Up to 12 months after last patient last visit |
Toxicity Rate |
Up to 12 months after last patient last visit |
Enrollment
49
Condition
Intervention
Intervention Type
Drug
Intervention Name
Description
Participants receive Anlotinib 12 mg p.o, qd on Days 1-14 of each 3-week cycle until progressive disease or unacceptable toxicity plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
Arm Group Label
Experimental: Anlotinib plus Pembrolizumab
Intervention Type
Biological
Intervention Name
Description
Participants receive Anlotinib 12 mg p.o, qd on Days 1-14 of each 3-week cycle until progressive disease or unacceptable toxicity plus pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
Arm Group Label
Experimental: Anlotinib plus Pembrolizumab
Eligibility
Criteria
Inclusion Criteria:
1. volunteered to join the study, signed the informed consent, had good compliance and
cooperated with the follow-up.
2. age: ≥18 years old.
3. Histologically or cytologically confirmed locally advanced NSCLC(not suitable for or
refuse to do radical radiotherapy and chemotherapy)/advanced NSCLC, have not
previously received systemic treatment for locally advanced or advanced NSCLC. The
completion time of previous neoadjuvant / adjuvant treatment for recurrent subjects
should be ≥ 6 months.
4. Negative in EGFR,ALK and ROS1(tumor tissue sample results).
5. Has tumor tissue that demonstrates PD-L1 expression in ≥1% of tumor cells (TPS≥1%) as
assessed by immunohistochemistry (IHC) 22C3 pharmDx assay at a central laboratory.
6. Diagnosed with advanced or recurrent NSCLC through pathology, with measurable
nidus(using RECIST 1.1).
7. Has a life expectancy of ≥3 months.
8. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
9. Has adequate organ function:
1. .HB≥90g/L;
2. ANC≥1.5×109/L;
3. PLT≥100×109/L;
4. WBC≥4.0×109/L and ≤15×109/L;
5. ALT and AST≤1.5×ULN(≤5×ULN in patients with liver metastases);
6. ALP≤2.5×ULN;
7. TBiL≤1.5×ULN;
8. ALB≥30g/L;
9. TSH≤ULN(If abnormal, T3 and T4 levels should be examined; If T3 and T4 levels are
normal, they can be enrolled);
10. Cr≤1.5×ULN,and CrCL≥60mL/min(Cockcroft-Gault).
10. The woman patients of childbearing age who must agree to take contraceptive methods
(e.g. intrauterine device, contraceptive pill or condom) during the research and
within another 4 months after it; who are not in the lactation period and examined as
negative in blood serum test or urine pregnancy test within 7 days before the
research; The man patients who must agree to take contraceptive methods during the
research and within another 120 days after it.
Exclusion Criteria:
1. Has an active autoimmune disease that has required systemic treatment. Replacement
therapy is not considered a form of systemic treatment and is allowed.
2. Is receiving systemic steroid therapy within 3 days before the first dose of study
treatment.
3. Live vaccines were administered within 4 weeks or possibly during the study.
4. Gene test results of tissue or blood samples confirmed the existence of EGFR, ALK and
ROS1 variants.
5. CT or MRI showed that the distance between the tumor focus and the large blood vessel
was less than or equal to 5 mm, or there was a large local invasion Blood vessels, or
central tumor with high risk of bleeding, or obvious cavitary or necrotic tumor of
lung.
6. Has active central nervous system metastasis (subjects who have completed treatment 21
days before randomization and have stable symptoms can be enrolled, but they need to
be confirmed by imaging evaluation as no active bleeding symptoms, and have stopped
systemic agitation Hormone therapy: dosage > 10mg / day prednisone or other effective
hormones.
7. Has received prior therapy with Anlotinib, anti-PD-1(L1) or anti-CTLA-4 agents.
8. Has a known history of an additional malignancy, except if the participant has
undergone potentially curative therapy with no evidence of that disease recurrence for
≥5 years since initiation of that therapy.
9. Has significant cardiovascular impairment, such as a history of congestive heart
failure greater than New York Heart Association Class II, unstable angina, myocardial
infarction within 12 months of the first dose of study treatment, or cardiac
arrhythmia associated with hemodynamic instability.
10. Has uncontrolled blood pressure (defined as systolic pressure≥140 mm Hg or diastolic
pressure≥90 mm Hg).
Has had an allogeneic tissue/solid organ transplant.
11. Abnormal coagulation (INR > 1.5 or PT > ULN + 4S or APTT > 1.5 ULN), with bleeding
tendency or undergoing thrombolysis or anticoagulation. Note: on the premise of INR ≤
1.5, it is allowed to use low-dose heparin (daily dosage for adults is 6000-12000 U)
or low-dose aspirin (daily dosage ≤ 100mg) for prevention purposes.
12. Has arterial/venous thrombosis within 6 months, such as cerebrovascular accidents
(including temporary ischemic stoke), deevenous thrombosis, and pulmonary embolism.
13. Has had clinically significant hemoptysis within 3 months before the study (more than
50ml hemoptysis per day); or clinically significant bleeding symptoms or clear
bleeding tendency (such as gastrointestinal bleeding, bleeding gastric ulcer,
Gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood + + or above
in baseline, or suffer from vasculitis, etc.
14. Urine routine indicates urine protein ≥ + +, or confirms 24-hour urine protein content
≥ 1.0g.
15. Has congenital or acquired immune deficiency (such as HIV infection), or active
hepatitis.
16. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated
drainage.
17. Take major surgical treatments, open biopsy, or get overt traumatic injury within 28
days before enrollment.
18. Has a previous and current history of pulmonary fibrosis, interstitial pneumonia,
pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung
function, etc.
19. Has received allogeneic cell / tissue / organ transplantation.
20. According to the judgment of the researcher, there are other factors that may cause
the study to be forced to terminate halfway, For example, other serious diseases
(including mental diseases) need to be treated in combination, with serious laboratory
abnormalities, and Court or social factors.
Gender
All
Minimum Age
18 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
LI zhang, master |
Principal Investigator |
Peking Union Medical College Hospital, Beijing, China |
Overall Contact
Location
Facility |
Status |
Contact |
Peking Union Medical College Hospital Beijing Beijing 100730 China |
Recruiting |
Location Countries
Country
China
Verification Date
2019-11-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Peking Union Medical College Hospital
Investigator Full Name
Li Zhang
Investigator Title
professor
Has Expanded Access
No
Condition Browse
Number Of Arms
1
Intervention Browse
Mesh Term
Pembrolizumab
Arm Group
Arm Group Label
Experimental: Anlotinib plus Pembrolizumab
Arm Group Type
Experimental
Firstreceived Results Date
N/A
Patient Data
Sharing Ipd
Undecided
Firstreceived Results Disposition Date
N/A
Study Design Info
Intervention Model
Single Group Assignment
Primary Purpose
Treatment
Masking
None (Open Label)
Study First Submitted
November 13, 2019
Study First Submitted Qc
November 13, 2019
Study First Posted
November 15, 2019
Last Update Submitted
November 13, 2019
Last Update Submitted Qc
November 13, 2019
Last Update Posted
November 15, 2019
ClinicalTrials.gov processed this data on December 05, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.