Umbrella Trial of Adjuvant Therapy in Completely Resected High-risk Stage IA-IB NSCLC: Focus on Driver Mutations

NCT06955325 | Not Yet Recruiting Phase 3

• 1 other identifier: UPLIFT
• Study Type: interventional
• Target: 270
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study explores how adjuvant therapy affects survival in completely resected high-risk stage IA-IB NSCLC patients with different driver gene mutations.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Disease-Free Survival (DFS)

  Disease-free survival (DFS) is defined as the time from randomization to the first documented disease recurrence (local relapse or distant metastasis confirmed by imaging or pathology) or death from any cause, whichever occurs first. Participants without documented recurrence or death at the time of analysis will be censored at their last disease assessment date.

  From randomization until disease recurrence or death (up to approximately 5 years)

Secondary Outcomes (3)

• Overall Survival (OS)

  From randomization to death or last follow-up (up to approximately 5 years)

• Central Nervous System Disease-Free Survival (CNS DFS)

  From randomization until CNS progression or death, whichever occurs first (up to approximately 5 years)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]

  From date of randomization up to approximately 5 years

Study Arms (2)

Adjuvant therapy

EXPERIMENTAL

Drug: Icotinib; Drug: Rezivertinib; Drug: Ensartinib; Drug: Benmelstobart

Observation

NO INTERVENTION

Interventions

Icotinib DRUG

Oral icotinib tablets (125 mg) administered three times daily (TID) for up to 1 year or until disease recurrence or unacceptable toxicity. Icotinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations.

Adjuvant therapy

Rezivertinib DRUG

Oral rezivertinib capsules (100 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Rezivertinib is an EGFR tyrosine kinase inhibitor targeting EGFR-sensitizing mutations.

Adjuvant therapy

Ensartinib DRUG

Oral ensartinib capsules (225 mg) taken once daily (QD) for up to 1 year or until disease recurrence or unacceptable toxicity. Ensartinib is an ALK/ROS1 tyrosine kinase inhibitor designed to inhibit ALK/ROS1 fusion-driven NSCLC.

Adjuvant therapy

Benmelstobart DRUG

Intravenous infusion of bemosumab 1200 mg every 3 weeks (Q3W). Treatment continues for up to 4 cycles initially, and may be extended (maintenance) for up to 3 years or until disease recurrence or unacceptable toxicity. Bemosumab is a monoclonal antibody under investigation for immunotherapy in NSCLC.

Adjuvant therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years and able to provide written informed consent.
• Primary non-squamous NSCLC confirmed by pathology, with no brain metastases.
• Complete R0 surgical resection (lobectomy, segmentectomy, or pneumonectomy) of stage IA or IB NSCLC (AJCC 8th edition).
• High-risk disease (one or more): low differentiation, solid/micropapillary/complex glandular patterns, vascular invasion, visceral pleural invasion, alveolar space spread, or intermediate/high risk on 14-gene test.
• Documented driver gene status (EGFR mutation, ALK/ROS1 fusion, or wild-type) via postoperative tumor sample.
• ECOG performance status 0 or 1, with stable condition over the last two weeks.
• Surgery within 4-10 weeks before starting treatment, with full recovery.
• Adequate organ function as per protocol-defined labs.
• Negative pregnancy test (if applicable) and use of effective contraception during and 3 months after treatment.

You may not qualify if:

• Evidence of unresectable/metastatic NSCLC, incomplete resection (R1/R2), or wedge resection only.
• Prior systemic therapy (e.g., chemotherapy, targeted therapy, immunotherapy) for the current NSCLC.
• Major surgery (excluding lung cancer surgery) within 3 weeks before first study dose.
• Planned concurrent anti-cancer therapy (chemo, radiotherapy, or targeted therapy) during the study.
• Clinically significant cardiac disorders (e.g., poorly controlled hypertension, recent MI or stroke, prolonged QTc).
• History or suspicion of interstitial lung disease requiring treatment.
• Active or uncontrolled infection (e.g., hepatitis B with detectable HBV DNA, hepatitis C, HIV, active TB).
• Severe GI conditions impairing drug absorption (e.g., Crohn's, ulcerative colitis).
• Use of strong CYP3A inducers/inhibitors within 1 week or ongoing need for warfarin.
• Participation in another interventional trial within 4 weeks or receipt of a live vaccine within 180 days.
• Any condition that may compromise adherence or safety, per investigator judgment.

Sponsors & Collaborators

• The First Affiliated Hospital of Guangzhou Medical University: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

icotinib; rezivertinib; ensartinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Head of Thoracic Surgery, Principal Investigator, Clinical Professor

Study Record Dates

• First Submitted: April 16, 2025
• First Posted: May 2, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2035
• Last Updated: May 6, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share