Exploring afatinib for advanced lung cancer with specific mutations

An Open-label Phase II Study of EGFR TKI in Patients With Advanced NSCLC Harbouring EGFR Mutations Categorized According to Structural Based Classification

This study is testing if the drug afatinib can help people with advanced lung cancer that has a specific mutation feel better and manage their disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 21 Years to 99 Years
• Sex: All
• Sponsor: National University Hospital, Singapore (Academic / other)
• Drugs / interventions: afatinib, chemotherapy, radiation
• Locations: 1 site (Singapore)
• Trial ID: NCT06062823 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of afatinib in patients with advanced non-small cell lung cancer (NSCLC) that have the EGFR PACC mutation subtype. It is a multi-center, open-label, phase II study where eligible participants will receive afatinib at a daily dose of 40mg until disease progression or other discontinuation criteria are met. Patients will undergo baseline assessments, regular clinical evaluations, and imaging tests throughout the treatment period to monitor their health and response to the medication.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 21 and older with histologically or cytologically confirmed advanced NSCLC and a detectable PACC mutation.

Not a fit: Patients with prior systemic therapy for advanced stage NSCLC or those without the specific EGFR PACC mutation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced NSCLC harboring EGFR PACC mutations.

How similar studies have performed: While studies on EGFR mutations in NSCLC have shown promise, the specific focus on the PACC mutation subtype with afatinib is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Histological or cytologically confirmed NSCLC.
2. No prior systemic therapy for advanced stage disease.
3. 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).
4. The presence of measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria (28).
5. Estimated life expectancy of at least 3 months.
6. ECOG performance status 0-1.
7. Age ≥21 years old.
8. 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
9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
10. For female patients of childbearing potential, have a negative pregnancy test documented ≤ 14 days prior to start of study medication.
11. Female patients of childbearing potential and male patients with partners of childbearing potential must agree to use a highly effective form of contraception with their sexual partners during the dosing period and for a period of at least 4 months after the end of treatment. Evidence of non-child-bearing potential is fulfilled by one of the following criteria at screening:

    * The post-menopausal period defined as age ≥50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments
    * Women \<50 years old they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range.
    * Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not a tubal ligation
12. Signed written informed consent.

Exclusion Criteria:

1. Prior EGFR TKI therapy.
2. 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.
3. 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.
4. Known leptomeningeal carcinomatosis.
5. 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.
6. Symptomatic and untreated spinal cord compression.
7. 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.
8. Had a cerebrovascular accident or transient ischemic attack within 6 months prior to enrolment.
9. 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.
10. Radiotherapy to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks before the study entry.
11. Inability to swallow oral medication.
12. Refractory nausea and vomiting, chronic gastrointestinal diseases or previous significant bowel resection that would preclude adequate absorption of afatinib.
13. Have a history or the presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis.
14. Have an ongoing or active infection, including, but not limited to, the requirement for intravenous antibiotics.
15. Have a known history of human immunodeficiency virus infection or active hepatitis B or C infection, active tuberculosis.
16. Have a known or suspected hypersensitivity to afatinib or its excipients.
17. Are pregnant, planning a pregnancy, or breastfeeding.
18. Males and females of reproductive potential who are not using an effective method of contraception and females who are pregnant or breastfeeding or have a positive serum pregnancy test prior to study entry.
19. Previous allogeneic bone marrow transplant.
20. Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the study treatment.

Where this trial is running

Singapore

• National University Hospital — Singapore, Singapore (Recruiting)

Study contacts

• Principal investigator: Kenneth Sooi — National University Hospital, Singapore
• Study coordinator: Kenneth Sooi

Conditions NSCLC; Afatinib; PACC mutation; EGFR mutations