Study of EGFR TKI in Patients With Advanced NSCLC Harbouring EGFR Mutations

NCT06062823 | Recruiting Phase 2

• 1 other identifier: NS01/02/23
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to explore the efficacy of afatinib in NSCLC harbouring EGFR PACC mutation subtype. The main question it aims to answer is: Afatinib is active in patients with advanced NSCLC harbouring EGFR PACC mutation subtype. Participants will undergo screening, follow by treatment if eligible for study participation and then enter follow up phase after study medication has stopped. Patients will take afatinib 40mg daily continuously, until the development of progressive disease or meeting discontinuation criteria. A treatment cycle is defined as 28 days.

Conditions

NSCLC

Keywords

Afatinib; PACC mutation; EGFR mutations

Outcome Measures

Primary Outcomes (1)

• Objective response rate

  Defined as best overall response (Complete Response or Partial Response) across all assessment time-points according to RECIST criteria v1.1

  At baseline and every 8 weeks for the first 6 cycles, every 12 weeks from cycle 7 to 12 and every 16 weeks from cycle 13 onwards (each cycle is 28 days)

Secondary Outcomes (5)

• Progression free survival

  within 4 weeks from starting treatment and every 8 weeks for the first 6 cycles, every 12 weeks from cycle 7 to 12 and every 16 weeks from cycle 13 onwards (each cycle is 28 days)

• Overall survival

  48 months

• Duration of response

  every 8 weeks for the first 6 cycles, every 12 weeks from cycle 7 to 12 and every 16 weeks from cycle 13 onwards (each cycle is 28 days)

• Time to treatment failure

  48 months

• Number of participant with treatment related toxicities

  48 months

Study Arms (1)

Afatinib

EXPERIMENTAL

Afatinib given as monotherapy daily in a 28-days cycle.

Drug: Afatinib 40 MG

Interventions

Afatinib 40 MG DRUG

Afatinib 40mg administered orally daily.

Also known as: Gilotrif

Afatinib

Eligibility Criteria

• Age: 21 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histological or cytologically confirmed NSCLC.
• No prior systemic therapy for advanced stage disease.
• Presence of a PACC mutation (detected either in blood or tumour) as defined by Robichaux et al (24). Compound mutations classified as PACC mutations are permitted (24).
• The presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (28).
• Estimated life expectancy of at least 3 months.
• ECOG performance status 0-1.
• Age ≥21 years old.
• Have adequate organ and hematologic function, as defined by:
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤3.0 x upper limit of normal (ULN) or ≤5 times ULN if related to liver metastases.
• Total serum bilirubin ≤1.5 × ULN (\<3.0 × ULN for patients with Gilbert syndrome)
• Creatinine clearance \>=45mL/min (Cockcroft Gault)
• Absolute neutrophil count ≥1.5 × 10\^9/L
• Platelet count ≥100 × 10\^9/L
• Hemoglobin ≥ 9.0 g/dL
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

You may not qualify if:

• Prior EGFR TKI therapy.
• Prior chemotherapy for Stage IIIB/IV adenocarcinoma of the lung. Neo-/adjuvant chemotherapy, CT-RT or RT is permitted if it has been elapsed for ≥12 months prior to disease progression.
• Have been diagnosed with another primary malignancy other than NSCLC, except for adequately treated non melanoma skin cancer or cervical cancer in situ; definitively treated non metastatic prostate cancer; or patients with another primary malignancy who are definitively relapse-free with at least 3 years elapsed since the diagnosis of the other primary malignancy.
• Known leptomeningeal carcinomatosis.
• Unstable spinal cord compression/brain metastases unless asymptomatic and not requiring steroids for at least 2 weeks prior to the start of study treatment. For patients with brain metastases, gamma knife or stereotactic brain surgery is allowed prior to study treatment.
• Symptomatic and untreated spinal cord compression.
• Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: myocardial infarction within 6 months prior to study enrolment; unstable angina within 6 months prior to study enrolment; congestive heart failure within 6 months prior to study enrolment; history of clinically significant atrial arrhythmia (including clinically significant bradyarrhythmia), as determined by the treating physician; any history of clinically significant ventricular arrhythmia; prolonged QTc.
• Had a cerebrovascular accident or transient ischemic attack within 6 months prior to enrolment.
• Major surgery within 4 weeks of starting study treatment and patients must have recovered from any effects of any major surgery. Minor surgery is allowed.
• Radiotherapy to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks before the study entry.
• Inability to swallow oral medication.
• Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection that would preclude adequate absorption of afatinib.
• Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
• Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
• Have a known history of human immunodeficiency virus infection or active hepatitis B or C infection, active tuberculosis.

Sponsors & Collaborators

• National University Hospital, Singapore: lead

Study Sites (1)

National University Hospital

Singapore, Singapore

RECRUITING

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MeSH Terms

Interventions

Afatinib

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kenneth Sooi

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kenneth Sooi

CONTACT

+65 6908 2222; kenneth_sooi@nuhs.edu.sg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: October 2, 2023
• Study Start: March 25, 2024
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 24, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)