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

Official title

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

Overview

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

Interventions

• 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.
• Biological luvometinib + anlotinib
  in this part, patients will receive the combined treatment of luvometinib and anlotinib at the recommended doses.

Primary outcome measures

• the objective response rate (ORR) per RECIST v1.1 [Time frame: up to 24 months]

Secondary outcome measures (6)

• Duration of overall response (DOR) [Time frame: up to 24 months]
• Time to response (TTR) [Time frame: up to 24 months]
• Disease Control Rate (DCR) [Time frame: up to 24 months]
• Progress Free Survival (PFS) [Time frame: up to 24 months]
• safety of the combination therapy of luvometinib and anlotinib [Time frame: up to 24 months]
• PK of the combination therapy of luvometinib and anlotinib [Time frame: up to 24 months]

Eligibility criteria

Inclusion criteria

• aged between ≥ 18 years and ≤75 years; regardless of male or female.
• 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.
• KRAS mutation positive.
• 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:

• Prior treatment with MEK inhibitors、anlotinib or other VEGFR-TKI(such as cabozantinib, sorafenib, apatinib,etc);
• 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;
• 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).
• 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;
• Radical radiotherapy within 28 days prior to the first dose; palliative radiotherapy allowed if ≥14 days before first dose;
• 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;
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Chest Hospital — Shanghai

Identifiers

NCT: NCT07562581 · FCN-159-011

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗