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

NCT04164745 | Unknown Phase 2

• 1 other identifier: ALTER-L037
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

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).

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) as assessed by RECIST 1.1

  PFS is defined as the time from date of enrollment to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurs first per RECIST 1.1.

  Up to approximately 24 months

Secondary Outcomes (5)

• 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

Study Arms (1)

Experimental: Anlotinib plus Pembrolizumab

EXPERIMENTAL

Drug: Anlotinib, oral capsule; Biological: Pembrolizumab

Interventions

Anlotinib, oral capsule DRUG

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).

Experimental: Anlotinib plus Pembrolizumab

Pembrolizumab BIOLOGICAL

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).

Experimental: Anlotinib plus Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• volunteered to join the study, signed the informed consent, had good compliance and cooperated with the follow-up.
• age: ≥18 years old.
• 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.
• Negative in EGFR,ALK and ROS1(tumor tissue sample results).
• 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.
• Diagnosed with advanced or recurrent NSCLC through pathology, with measurable nidus(using RECIST 1.1).
• Has a life expectancy of ≥3 months.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Has adequate organ function:
• HB≥90g/L;
• ANC≥1.5×109/L；
• PLT≥100×109/L；
• WBC≥4.0×109/L and ≤15×109/L;
• ALT and AST≤1.5×ULN(≤5×ULN in patients with liver metastases);
• ALP≤2.5×ULN;

You may not qualify if:

• Has an active autoimmune disease that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.
• Is receiving systemic steroid therapy within 3 days before the first dose of study treatment.
• Live vaccines were administered within 4 weeks or possibly during the study.
• Gene test results of tissue or blood samples confirmed the existence of EGFR, ALK and ROS1 variants.
• 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.
• 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.
• Has received prior therapy with Anlotinib, anti-PD-1(L1) or anti-CTLA-4 agents.
• 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.
• 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.
• 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.
• 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.
• Has arterial/venous thrombosis within 6 months, such as cerebrovascular accidents (including temporary ischemic stoke), deevenous thrombosis, and pulmonary embolism.
• 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.
• Urine routine indicates urine protein ≥ + +, or confirms 24-hour urine protein content ≥ 1.0g.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

MeSH Terms

Interventions

anlotinib; pembrolizumab

Study Officials

• LI zhang, master

  Peking Union Medical College Hospital, Beijing, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

xiaoxia cui, master

CONTACT

13126708633; cuixiaoxia8462@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 13, 2019
• First Posted: November 15, 2019
• Study Start: November 16, 2019
• Primary Completion: November 16, 2021
• Study Completion: November 16, 2022
• Last Updated: November 15, 2019

Record last verified: 2019-11

Locations

CN (1)