Anlotinib Plus Immune Checkpoint Inhibitors for Lung Cancer (ATHENA)

Anlotinib With or Without Immune Checkpoint Inhibitors in Standard Chemo-immunotherapy Failed Advanced Non-small Cell Lung Cancer

This study aims to explore the efficacy of Anlotinib with or without Immune Checkpoint Inhibitor in Standard Chemo-immunotherapy Failed Advanced NSCLC.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Anlotinib; Drug: Anlotinib plus the same Immune Checkpoint Inhibitors.; Drug: Anlotinib plus the new Immune Checkpoint Inhibitors.

Detailed Description

This study aims to explore the efficacy of Anlotinib with or without Immune Checkpoint Inhibitor in Standard Chemo-immunotherapy Failed Advanced NSCLC. The primary endpoint was PFS.

• Study Type: Interventional
• Enrollment (Estimated): 1200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Yongchang Zhang, MD; Phone Number: +861383123436 +8613873123436; Email: zhangyongchang@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410013
      • Recruiting
      • Yongchang Zhang
      • Contact: Yongchang Zhang, MD; Phone Number: +8613873123436 +8613873123436; Email: zhangyongchang@csu.edu.cn

Participation Criteria

Eligibility Criteria

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

Study Population

Standard Chemotherapy Failure Advanced NSCLC

Description

Inclusion Criteria:

1. Understand the requirements and contents of the clinical trial, and provide a signed and dated informed consent form.
2. Age ≥ 18 years.
3. Histopathology or cytology confirmed lung cancer
4. Failed from first line Chemo-immunotherapy.
5. ECOG 0-1.
6. Predicted survival ≥ 12 weeks.
7. Adequate bone marrow hematopoiesis and organ function
8. Presence of measurable lesions according to RECIST 1.1.
9. Subjects with stable brain metastases may be included in the study.

Exclusion Criteria:

1. Subjects who have received any of the following treatments must be excluded:

   • Treatment with molecules such as EGFR, VEGFR antibodies within 4 weeks prior to the first dose of study drug.
   • Have received radiation within 14 days prior to the first dose or have not recovered from radiation-related toxicity. Chest and extra-brain palliative radiotherapy, stereotactic radiosurgery, and stereotactic body radiotherapy may be performed 7 days prior to the first dose.
   • Ongoing (or inability to discontinue) possibly potent CYP1A2, CYP3A inhibitor (1 week), or inducer (2 weeks) drug therapy or herbal supplements within 1-2 weeks prior to the first dose.
2. Presence of spinal cord compression or meningeal metastasis.
3. History of other malignant tumors within 2 years.
4. Adverse events (except alopecia of any degree) of CTCAE > grade 1 due to prior treatment (e.g., adjuvant chemotherapy, radiotherapy, etc.) prior to the first dose.
5. History of stroke or intracranial hemorrhage within 6 months prior to the first dose.
6. The presence of any severe or poorly controlled systemic disease, including poorly controlled hypertension and active bleeding in the judgment of the investigator.
7. Subjects with persistent or active infection, including but not limited to hepatitis B (HBV), hepatitis C (HCV), human immunodeficiency virus (HIV) and COVID-19 infection.
8. Heart-related diseases or abnormalities
9. Past history of interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis requiring steroid therapy or interstitial lung disease with active clinical symptoms, immune pneumonia caused by immunotherapy.
10. Refractory nausea and vomiting, chronic gastrointestinal disease, difficulty swallowing drugs, or inability to adequately absorb sunvozertinib or anlotinib due to previous bowel resection.
11. Live vaccine was given 2 weeks before the first medication.
12. Women who are breastfeeding or pregnant.
13. Hypersensitivity to the test drug and the ingredients.
14. Other conditions assessed by the investigator to be unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A: Anlotinib with the same Immune Checkpoint Inhibitors.; Anlotinib plus Immune Checkpoint Inhibitors which has been used in first line treatment.	Drug: Anlotinib plus the same Immune Checkpoint Inhibitors.; Anlotinib, 8mg po qd, D1-D14 every 21days.; Other Names: Pembrolizumab, Sintilimab etc. have been used in the previous treatment.
Experimental: Cohort B: Anlotinib with the new Immune Checkpoint Inhibitors.; Anlotinib plus Immune Checkpoint Inhibitors which has not been used in first line treatment.	Drug: Anlotinib plus the new Immune Checkpoint Inhibitors.; Anlotinib, 8mg po qd, D1-D14 every 21days.; Other Names: Pembrolizumab, Sintilimab etc. have not been used in the previous treatment.
Experimental: Cohort C: Anlotinib Monotherapy.; Anlotinib Monotherapy.	Drug: Anlotinib; Anlotinib, 8mg po qd, D1-D14 every 21days.; Other Names: Anlotinib monotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival time (PFS)	Progression free survival time define as first dose to first documented disease progression assessed by investigator or death due to any cause.	Time from first subject dose to study completion, or up to 36 month.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective response rate define as the proportion of subjects who have a complete response (CR) or a partial response (PR).	Time from first subject dose to study completion, or up to 36 month.
Overall survival (OS)	To assess overall survival, define as first dose to the death of the subject due to any cause.	Time from first subject dose to study completion, or up to 36 month.

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital
• Investigators: Principal Investigator: Yongchang Zhang, MD, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2020
• Primary Completion (Estimated): March 24, 2028
• Study Completion (Estimated): March 24, 2029

Study Registration Dates

• First Submitted: March 24, 2020
• First Submitted That Met QC Criteria: March 24, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 1, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Anlotinib, Immune Checkpoint Inhibitor, NSCLC
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 20200113

Drug and device information, study documents

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