Anlotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer

Durvalumab+ Anlotinib + Standard Chemotherapy in First-line Treatment of Extensive Small-cell Lung Cancer: a Single-arm Phase II Clinical Study

Small Cell Lung cancer (SCLC) is a highly aggressive tumor that accounts for about 15 percent of all lung cancer cases. SCLC disease progresses rapidly, and about 2/3 of the patients have extensive stage (ES-SCLC) at the time of diagnosis, with extremely poor prognosis. However, the overall survival (OS) of ES-SCLC patients was not significantly prolonged, with platinum combined with etoposide chemotherapy as the standard treatment. In recent years, the emergence of Immune checkpoint inhibitor (ICI) has made the treatment of ES-SCLC appear at the dawn. In Impower133 study, Atezolizumab combined with chemotherapy significantly prolonged OS(median OS 12.3 months vs 10.3 months, HR=0.70, 95%CI 0.54-0.91, P = 0.007). Durvalumab combined with chemotherapy (CASPIAN study) is the first study in 20 years in which the total survival time of ES-SCLC treated by first-line therapy is 13 months, and there is no significant increase in adverse reactions compared with chemotherapy. Therefore, in 2019, NCCN also recommended Atezolizumab or Durvalumab+ EC regimens as a category 1 preferred option for first-line treatment of ES-SCLC.

Study Overview

• Status: Completed
• Conditions: SCLC, Extensive Stage
• Intervention / Treatment: Drug: Anlotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer

Detailed Description

Small Cell Lung cancer (SCLC) is a highly aggressive tumor that accounts for about 15 percent of all lung cancer cases. SCLC disease progresses rapidly, and about 2/3 of the patients have extensive stage (ES-SCLC) at the time of diagnosis, with extremely poor prognosis. However, the overall survival (OS) of ES-SCLC patients was not significantly prolonged, with platinum combined with etoposide chemotherapy as the standard treatment. In recent years, the emergence of Immune checkpoint inhibitor (ICI) has made the treatment of ES-SCLC appear at the dawn. In Impower133 study, Atezolizumab combined with chemotherapy significantly prolonged OS(median OS 12.3 months vs 10.3 months, HR=0.70, 95%CI 0.54-0.91, P = 0.007). Durvalumab combined with chemotherapy (CASPIAN study) is the first study in 20 years in which the total survival time of ES-SCLC treated by first-line therapy is 13 months, and there is no significant increase in adverse reactions compared with chemotherapy. Therefore, in 2019, NCCN also recommended Atezolizumab or Durvalumab+ EC regimens as a category 1 preferred option for first-line treatment of ES-SCLC.

Although THE TMB of SCLC is higher in solid tumors, the objective remission rate (ORR) of SCLC using PD-1 or PD-L1 inhibitors is slightly lower than that of non-small cell lung cancer, and frequent drug resistance becomes the bottleneck of treatment. Some recent studies have shown that anti-angiogenesis drugs can also reverse the immunosuppressive state of tumor microenvironment while anti-tumor therapy, and improve the efficacy of ICI, so as to play a synergistic role. Therefore, anti-angiogenesis therapy combined with immunotherapy is expected to be a new strategy for the treatment of SCLC. Amlotinib is a multi-target anti-angiogenic drug, which has been approved for third-line treatment of SCLC with mild adverse reactions. Anlotinib combined with Durvalumab may have a synergistic antitumor effect, but no studies have been reported so far. Therefore, on the basis of the CASPIAN research study, we designed the Durvalumab + chemotherapy + ernesto, first-line treatment for extensive stage small cell lung cancer with single arm, open, multicenter, phase II clinical research, expected in domestic five cancer center, into the group of 120 ES - SCLC patients with untreated, research Durvalumab + chemotherapy + ROM for efficacy and safety of Ann, and further explore the curative effect of predictive biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Henan
    • Luoyang, Henan, China, 471000
      • Sixth People's Hospital of Luoyang
    • Zhengzhou, Henan, China, 450000
      • Henan Tumor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed primary treatment of ES-SCLC (small cell lung cancer) in male or female patients aged ≥18 and <75 years.
• The ECOG energy status is 0 or 1.
• Appropriate hematologic and terminal organ functions.

Exclusion Criteria:

• Prior to systemic treatment, the patient had a history of chest radiation therapy or planned to undergo intensive chest radiation therapy.
• Spinal cord compression not explicitly treated by surgery and/or radiation, or previously diagnosed and treated, with no evidence of clinical stabilization of >2 weeks prior to randomization. Active brain metastases (stable brain metastases may be admitted after treatment) occurred within one month prior to enrollment.
• Uncontrolled or symptomatic hypercalcemia, active tuberculosis, major cardiovascular disease.
• A history of autoimmune diseases, idiopathic pulmonary fibrosis, organized pneumonia, HIV positive, active hepatitis B, radiographic findings of tumor infiltration of the large vessels in the chest and significant pulmonary cavitation lesions, a previous history of hypertensive crisis or hypertensive encephalopathy.
• History of hemoptysis within 1 month prior to randomization (≥0.5 TSP of bright red blood per episode).
• Major surgery within 28 days or needle core biopsy or other minor surgical procedures within 7 days.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Outcome of Durvalumab-Etoposide-platinum in untreated ES-SCLC(CASPIAN trial); The outcome of CASPIAN

Drug: Anlotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer; This trial is single-armed IIb stage clinical trial to study the efficacy and safety of Alotinib Plus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer . We use the outcome of CASPIAN trial as control group. The primary endpoint is ORR according to the RECIST 1.1, and secondary endpoints are PFS, OS, satety and life quality.; Other Names: Anlotinib Plus Durvalumab-Platinum-Etoposide Versus Durvalumab-Platinum-Etoposide in First-line Treatment Extensive Small-cell Lung Cancer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	From date of the first dose of induction to date of objective disease progression or death, whichever came first,	Assessed up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS )	Time from the first treatment to death from any cause or the end of the study	From date of randomization until the date of first documented date of death from any cause, assessed up to 60 months
Objective Response Rate (ORR )	Proportion of patients with reduction in stable in tumor burden of a predefined amount，Baseline until partial response (PR) or complete response (CR), whichever occurs first，assessed up to 12 months	From the date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 60 months.
Disease Control Rate (DCR)	Proportion of patients with reduction in stable in tumor burden of a predefined amount，Baseline until partial response (PR) ,complete response (CR) or stable disease (SD), whichever occurs first，assessed up to 12 months	From the date of first dose until the date of first documented disease progression or death from any cause, whichever occurs first, assessed up to 60 months.
Time To Response (TTR)	Time from the initiation of treatment to the first observation of disease response	Up to 60 months
Duration of response (DoR)	Time from first documented evidence of CR or PR until PD or death, whichever occurred first	Up to 60 month
PFS Rate	The percentage of participants with no progression or death at 12 or 24 months	UP to 60 months
OS rate	The percentage of participants still alive at 12 or 24 months	Up to 60 months
Safety	Adverse events (AEs) were monitored and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0).	Up to 60 months

Collaborators and Investigators

• Sponsor: Henan Cancer Hospital
• Investigators: Principal Investigator: Yanqiu Zhao, MS, Henan Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Actual): June 30, 2024
• Study Completion (Actual): June 30, 2024

Study Registration Dates

• First Submitted: November 12, 2020
• First Submitted That Met QC Criteria: December 2, 2020
• First Posted (Actual): December 9, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: small cell lung cancer, Durvalumab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; anlotinib
• Other Study ID Numbers: HXNI-DA001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No