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

NCT07780578 | Not Yet Recruiting Phase 2

• 1 other identifier: PLB1004-IIT-NSCLC-1
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer (NSCLC, Locally Advanced or Metastatic, Second-line

Keywords

Andamertinib; Anlotinib; Third-generation EGFR-TKI; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• ORR

  12 months after the last subject participating in

• DCR

  12 months after the last subject participating in

• DoR

  12 months after the last subject participating in

• OS

  24 months after the last subject participating in

• The incidence of Subjects With Treatment-Emergent Adverse Event (TEAE)

  24 months after the last subject participating in

Study Arms (1)

Andamertinib + Anlotinib

EXPERIMENTAL

Drug: Andamertinib; Drug: Anlotinib

Interventions

Andamertinib DRUG

Andamertinib: 160mg, QD, Q3W

Andamertinib + Anlotinib

Anlotinib DRUG

Anlotinib: 12mg/10mg, QD, d1-d14, Q3W

Andamertinib + Anlotinib

Eligibility Criteria

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

You may qualify if:

• Able to understand and voluntarily sign the written informed consent form.
• Aged ≥ 18 years, male or female.
• 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.
• 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.
• 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.
• Patients with asymptomatic brain metastases, or brain metastases whose symptoms have stabilized after treatment.
• 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.

You may not qualify if:

• 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.
• 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.
• Central squamous-cell carcinoma with high risk of massive hemoptysis.
• 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.
• Prior treatment with sunvozertinib.
• 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.
• 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.
• \. Any of the following cardiac conditions:
• Mean QTcF (QTc corrected by Fridericia formula) from three screening ECGs \>470 ms at rest.
• 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).
• Risk factors for QTc interval prolongation: e.g., severe hypokalaemia, congenital long-QT syndrome, concomitant use of QTc-prolonging drugs.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, China

Location

Related Publications (1)

• [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.

  BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

anlotinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jialei Wang

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jialei Wang

CONTACT

+86-21-64175590; wangjialei@shca.org.cn

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: Chief physician

Study Record Dates

• First Submitted: August 19, 2026
• First Posted: August 21, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: August 25, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)