A Phase 2 Study of Luvometinib Combined With Anlotinib in KRAS-mutated NSCLC

A Multicenter, Open-label, Single-arm Phase 2 Study to Evaluate the Efficacy and Safety of Luvometinib Combined With Anlotinib in Patients With KRAS-mutated Metastatic Non-small Cell Lung Cancer

Aim to evaluate the efficacy and safety of luvometinib combined with anlotinib in patients with KRAS-mutated non-small cell lung caner

Study Overview

• Status: Not yet recruiting
• Conditions: Metastasis; Non-small Cell Lung Caner; KRAS-mutated; Previous Treamted
• Intervention / Treatment: Biological: luvometinib + anlotinib; Biological: luvometinib + anlotinib

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BAOHUI HAN; Phone Number: +86 13817833343; Email: 18930858216@163.com
• Study Contact Backup: Name: Wei Zhang; Phone Number: +86 18017321318; Email: zhwei2002@sjtu.edu.cn

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Shanghai Chest Hospital
      • Contact: BAOHUI HAN; Phone Number: +86 13817833343; Email: 18930858216@163.com
      • Contact: Wei Zhang; Phone Number: +86 18017321318; Email: zhwei2002@sjtu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. aged between ≥ 18 years and ≤75 years; regardless of male or female.
2. Histologically and/or cytologically confirmed diagnosis of non-small cell lung caner,and the clinical stage is IV(AJCC 4th）; Received at least one line of systemic treatment(including platinum-based chemotherapy ± PD-(L)1) during the stage IV, and disease progression occured during or after the treatment.
3. KRAS mutation positive.
4. ECOG score 0-1. 5. Expected survival time ≥ 3 months.

6．At least one intracranial measurable lesion according to RECIST v1.1 criteria.

7．Adequate organ function within 7 days before enrollment. 8. Recovery to ≤grade 1 or return to baseline from previous treatment-related adverse events (according to CTCAE 5.0), except for adverse events such as hair loss that are judged by the investigators to be safe and do not violate other inclusion criteria.

9. Avoid excessive exposure to sunlight, and be willing to use sufficient sunscreen when there is expected to be sunlight exposure.

10. Take contraceptive measures as required.

Exclusion Criteria

1．Patients who have previously received any of the following treatments:

1. Prior treatment with MEK inhibitors、anlotinib or other VEGFR-TKI(such as cabozantinib, sorafenib, apatinib,etc);
2. Major surgery within 28 days or minor surgery within 14 days prior to the first dose, or need to undergo major surgery during the study treatment;
3. Systemic anti-cancer treatment (including chemotherapy, targeted therapy, immunotherapy, and other clinical trial drug treatments) within 28 days prior to the first dose or within 5 drug half-lives (whichever is shorter).
4. Treatment with traditional Chinese medicine, Chinese patent medicine or modern Chinese medicine preparations with anti-tumor indications within 7 days prior to the first dose;
5. Radical radiotherapy within 28 days prior to the first dose; palliative radiotherapy allowed if ≥14 days before first dose;
6. Live or live-attenuated vaccine within 28 days prior to the first dose; other vaccines (e.g., inactivated COVID-19 vaccine) within 14 days prior to the first dose;

7. History of allogeneic organ transplantation or allogeneic stem cell transplantation, or autologous stem cell transplantation within 3 months prior to the first dose.

   2．Active CNS metastases; brainstem, leptomeningeal, spinal cord metastases or spinal cord compression.

   3.Small cell lung cancer (including mixed SCLC/NSCLC) or cavitary central squamous cell carcinoma.

   4.Receipt of ≥4 prior lines of systemic anticancer therapy. 5.Active autoimmune disease requiring systemic therapy in the past 2 years,except: stable disease on replacement therapy without systemic treatment; non-systemic dermatologic conditions (vitiligo, psoriasis) or alopecia.

   6.Active infection requiring systemic therapy within 2 weeks before first dose. 7.Uncontrolled hypertension. 8.Dysphagia, active gastrointestinal disease, malabsorption, or any condition impairing study drug absorption.

   9.Retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED), uncontrolled glaucoma, or other ocular disease interfering with ocular toxicity assessment.

   10.Current or previous idiopathic pulmonary fibrosis/pneumonitis; active ILD, pneumonitis (including clinically significant radiation pneumonitis), pulmonary fibrosis; history of tracheal fistula; continuous oxygen requirement due to severe dyspnea or respiratory insufficiency.

   11.Active HBV or HCV; known AIDS or positive HIV; active tuberculosis or syphilis.

   12.Tumor invasion into major vessels, heart, pericardium, trachea, esophagus, or high risk of esophagotracheal/esophagopleural fistula.

   13.Significant hemoptysis within 1 month before first dose; clinically significant bleeding, bleeding tendency, coagulopathy, or history of ≥Grade 3 thrombosis.

   14.Symptomatic or recurrent pleural effusion, ascites, or pericardial effusion requiring frequent drainage.

   15.Other malignancy diagnosed within 5 years before first dose.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm1: safety run-in part; Oral treatment with luvometinib + anlotinib combination, including different doses.	Biological: luvometinib + anlotinib; Dose A：luvometinib 8mg and anlotinib 8mg; Dose B1：luvometinib 12mg and anlotinib 8mg; Dose B2: luvometinib 8mg and anlotinib 10mg; Dose C: luvometinib 12mg and anlotinib 10mg.; Other Names: FCN-159+anlotinib; Biological: luvometinib + anlotinib; in this part, patients will receive the combined treatment of luvometinib and anlotinib at the recommended doses.; Other Names: FCN-159+anlotinib
Experimental: Arm2: expansion part; Select the optimal doses of luvometinib + anlotinib combination from the safety run-in period and continue enrolling about 30 patients to evaluate the efficacy and further safety.	Biological: luvometinib + anlotinib; Dose A：luvometinib 8mg and anlotinib 8mg; Dose B1：luvometinib 12mg and anlotinib 8mg; Dose B2: luvometinib 8mg and anlotinib 10mg; Dose C: luvometinib 12mg and anlotinib 10mg.; Other Names: FCN-159+anlotinib; Biological: luvometinib + anlotinib; in this part, patients will receive the combined treatment of luvometinib and anlotinib at the recommended doses.; Other Names: FCN-159+anlotinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the objective response rate (ORR) per RECIST v1.1	ORR assessed per RECIST v1.1 criteria,and defined as the proportion of patients with confirmed complete response (CR) and partial response (PR)	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of overall response (DOR)	DOR is defined as the time from the date of the first CR or PR to the first recorded tumor progression or death (death due to any cause), whichever occurs earlier	up to 24 months
Time to response (TTR)	TTR is defined as the time from the first dose of the investigational drug to the first confirmed CR or PR	up to 24 months
Disease Control Rate (DCR)	DCR is defined as the proportion of patients with complete response (CR), partial response (PR) or stable disease(SD)	up to 24 months
Progress Free Survival (PFS)	PFS is defined as the time from the first dose to the first recorded progressive disease or death from any cause, whichever is first	up to 24 months
safety of the combination therapy of luvometinib and anlotinib	including the types and frequencies of adverse event (AE) that occurred during the treatment period, Serious adverse events (SAE), adverse events that led to reduction of dose, and adverse events that resulted in discontinuation of dose.	up to 24 months
PK of the combination therapy of luvometinib and anlotinib	including the types and frequencies of adverse event (AE) that occurred during the treatment period, Serious adverse events (SAE), adverse events that led to reduction of dose, and adverse events that resulted in discontinuation of dose.	up to 24 months

Collaborators and Investigators

• Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030

Study Registration Dates

• First Submitted: April 25, 2026
• First Submitted That Met QC Criteria: April 25, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

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

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; anlotinib
• Other Study ID Numbers: FCN-159-011

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No