The Study Of Andamertinib Plus Anlotinib In Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer

A Single Arm, Multicenter, Phase II Clinical Study to Evaluate the Efficacy and Safety of Andamertinib Combined With Anlotinib in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer Who Failed Prior First Line Third Generation EGFR TKI Therapy

This study is a single arm study to access the anti-tumor efficacy and safety of Andamertinib plus Anlotinib in patients with locally advanced or metastatic non-small cell lung cancer previously treated with third-generation EGFR-TKI.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer (NSCLC, Locally Advanced or Metastatic, Second-line
• Intervention / Treatment: Drug: Andamertinib; Drug: Anlotinib

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

Contacts and Locations

• Study Contact: Name: Jialei Wang; Phone Number: +86-21-64175590; Email: wangjialei@shca.org.cn

Study Locations

• China
  • Shanghai, China
    • Fudan University Shanghai Cancer Center
    • Contact: Jialei Wang; Phone Number: 18017312369; Email: wangjialei@shca.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to understand and voluntarily sign the written informed consent form.
2. Aged ≥ 18 years, male or female.
3. Non-small-cell lung cancer (NSCLC) confirmed histologically or cytologically, clinically diagnosed as unresectable and ineligible for curative concurrent chemoradiotherapy, including locally advanced (stage ⅢB/ⅢC), metastatic or recurrent (stage Ⅳ) NSCLC.
4. Harboring EGFR mutations (including exon19 deletions and exon21 L858R mutation), with documented disease progressed following only one prior line of third-generation EGFR-TKI therapy.
5. At least one measurable lesion per RECIST v1.1. Lesions previously irradiated cannot serve as target lesions unless definitive progression has occurred in the irradiated lesion.
6. Patients with asymptomatic brain metastases, or brain metastases whose symptoms have stabilized after treatment.
7. Laboratory values meeting all of the following criteria:

(1) Hemoglobin ≥100g/L (female), ≥110g/L (male). (2) Absolute neutrophil count ≥1.5×10⁹/L. (3) Platelet count ≥100×10⁹/L. (4) Serum creatinine ≤115 μmol/L, or creatinine clearance (CrCl) ≥60mL/min (Cockcroft-Gault formula).

(5) Total bilirubin ≤1.5×upper limit of normal (ULN). (6) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN; or ≤5×ULN for patients with liver metastases.

(7) Albumin ≥30g/L. 8. ECOG PS 0-1. 9. Expected survival ≥3 months. 10. Males with reproductive potential and females of child-bearing potential must agree to use effective contraception from the time of informed consent signing until 3 months after the last study drug administration. For females of child-bearing potential, serum pregnancy test must be negative within 7 days prior to the first study drug dose. Women with surgical sterilization or post-menopausal status are exempted.

Exclusion Criteria:

1. Diagnosis of other malignant diseases within 3 years prior to first study drug administration, except for radically treated basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, and/or radically resected carcinoma in-situ.
2. Presence of any of the following genetic alterations: ALK fusion, ROS1 fusion, BRAF V600 mutation, NTRK fusion, MET exon14 skipping mutation, MET amplification, RET fusion, KRAS G12C mutation, HER2 mutation, NRG1 fusion.
3. Central squamous-cell carcinoma with high risk of massive hemoptysis.
4. Toxicities from prior anti-tumour therapy have not recovered to Grade≤1, except for alopecia, fatigue and other toxicities judged by the investigator to carry low safety risk.
5. Prior treatment with sunvozertinib.
6. Major surgery (e.g., intrathoracic, intra-abdominal or pelvic surgery) within 4 weeks before first study drug administration, or resection for brain metastases within 2 weeks, with incomplete recovery from surgical adverse effects. Thoracoscopic biopsy and mediastinoscopy are not considered major surgery; subjects may be enrolled ≥1week after such procedures. Thoracic/abdominal effusion drainage and needle biopsy are not regarded as surgery.
7. Severe or uncontrolled systemic diseases, including but not limited to:

(1) Uncontrolled hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg despite treatment; antihypertensive agents may be initiated or adjusted prior to screening).

(2) Positive HIV antibody; or positive HCV antibody plus positive HCV-RNA; or positive HBsAg with HBV-DNA ≥500 IU/mL. Exception: subjects may be enrolled if HBV-DNA decreases to < 500 IU/mL and remains so for ≥2 weeks under antiviral therapy during screening, and antiviral therapy must be continued throughout the study. Subjects who require antiviral therapy at screening or in the past must maintain antiviral therapy for the whole study period.

(3) Active keratitis or ulcerative keratitis. (4) Active tuberculosis. (5) Active infection requiring systemic anti-infective therapy within 2 weeks prior to first study drug administration.

(6) Other severe physical or psychiatric illnesses or laboratory abnormalities that, in the investigators opinion, make study drug inappropriate or compromise protocol compliance.

8. Any of the following cardiac conditions:

1. Mean QTcF (QTc corrected by Fridericia formula) from three screening ECGs >470 ms at rest.
2. Significant arrhythmias including ventricular arrhythmias, pharmacologically uncontrolled supraventricular/nodal arrhythmias and other uncontrolled cardiac arrhythmias (e.g., complete left bundle-branch block, grade III atrioventricular block, grade II atrioventricular block, PR interval >250 msec).
3. Risk factors for QTc interval prolongation: e.g., severe hypokalaemia, congenital long-QT syndrome, concomitant use of QTc-prolonging drugs.
4. New York Heart Association (NYHA) congestive heart failure class ≥3; left ventricular ejection fraction (LVEF) <50% on echocardiogram.

9. History of interstitial lung disease, drug-induced interstitial lung disease, or radiation pneumonitis requiring steroid therapy; or ongoing medical intervention or active interstitial lung disease at present.

10. Coagulopathy or bleeding diathesis: arterial/venous thromboembolic events within 6 months before first study drug administration (including myocardial infarction, unstable angina, cerebrovascular accident or transient ischaemic attack, pulmonary embolism, severe deep-vein thrombosis or other serious thromboembolic events); life-threatening bleeding events requiring transfusion, surgery, local intervention or sustained medical treatment; or tumour invasion of major vessels judged by the investigator to confer high bleeding risk.

11. Dysphagia, active gastrointestinal disorders, or history of major gastrointestinal surgery that may substantially impair study-drug ingestion or absorption (e.g., ulcerative lesions, inability to swallow oral medication, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome).

12. Pleural, pericardial or peritoneal effusion requiring drainage and/or associated with dyspnoea within 4 weeks before first study drug administration.

13. Any clinically significant systemic disease requiring treatment as judged by the investigator, including but not limited to thyroid disorders (subjects with stable thyroid function on hormone-replacement therapy are eligible), organ transplantation recipients, psychiatric disorders, history of substance abuse, alcoholism or drug addiction.

14. Known hypersensitivity to the active substance or excipients of the study drug.

15. Pregnant or lactating females. 16. Currently participating in another investigational drug or device trial, or having received other investigational drugs/devices within 2 weeks before first study drug administration.

17. Cognitive impairment likely to limit understanding and execution of informed consent.

18. Any other conditions that may increase risks related to study-drug administration, confound interpretation of study results, poor subject compliance, or render the subject unsuitable for enrolment as judged by the investigator.

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
Experimental: Andamertinib + Anlotinib	Drug: Andamertinib; Andamertinib: 160mg, QD, Q3W; Drug: Anlotinib; Anlotinib: 12mg/10mg, QD, d1-d14, Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival (PFS per RECIST 1.1) is defined as the time from treatment to the date of first documentation of disease progression or death, whichever occurs first	12 months after the last subject participating in

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DoR	DoR (per RECIST 1.1) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first.	12 months after the last subject participating in
DCR	The proportion of subjects with complete response (CR), partial response (PR)and stable disease in(SD) in total subjects	12 months after the last subject participating in
ORR	The proportion of subjects with complete response (CR) and partial response (PR) in total subjects	12 months after the last subject participating in
OS	Defined as the time from treatment to all-cause death	24 months after the last subject participating in
The incidence of Subjects With Treatment-Emergent Adverse Event (TEAE)	TEAE will be defined as the adverse events (AEs) that occur between first dose of study drug administration and 28 days after the last dose of study drug administration that were absent before treatment or that worsened relative to pretreatment state.	24 months after the last subject participating in

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jialei Wang, Fudan University

Publications and helpful links

General Publications

• [1] Li K, Yang M, Liang N, et al. Determining EGFR-TKI sensitivity of G719X and other uncommon EGFR mutations in non-small cell lung cancer: Perplexity and solution (Review)[J]. Oncol. Rep., 2017, 37(3): 1347-1358. [2] NCCN Clinical Practice Guidelines in Oncology, Non-Small Cell Lung Cancer, Version 3.2022 [3] Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Non-Small-Cell Lung Cancer (2022 Edition) [4] Cheng Y, He Y, Li W, et al. Osimertinib versus comparator EGFR TKI as first-line treatment for EGFR-mutated advanced NSCLC: FLAUA China, a randomized study. Target Oncol, 2021, 16(2): 165-176. doi:10.1007/s11523-021-00794-6. [5] Hua-Jun Chen，Hai-Yan Tu，Yi-Long Wu et al. A phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001)，Journal of hematology & oncology, 2025 Jan 5;18(1):3. doi: 10.1186/s13045-024-01656-0. [6] Yu Hua，Minghui Liu，Jun Chen et al. Anlotinib Plus Osimertinib in Osimertinib-Resistant Nonsquamous Nonsmall Cell Lung Cancer With Gradual Progression: A Retrospective Study，Thoracic cancer, 2025 May;16(10):e70071. doi: 10.1111/1759-7714.70071.

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: August 19, 2026
• First Submitted That Met QC Criteria: August 19, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): August 25, 2026
• Last Update Submitted That Met QC Criteria: August 22, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Anlotinib; Third-generation EGFR-TKI; Andamertinib
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; anlotinib
• Other Study ID Numbers: PLB1004-IIT-NSCLC-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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