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NSCLCPhase 2NCT06062823

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

A Phase 2 study testing Afatinib 40 MG in people with NSCLC, run by National University Hospital, Singapore at 1 site in Singapore.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 21 to 99 years
Conditions the study is for
NSCLC
What is being tested?
Afatinib 40 MG
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
1 siteSingapore
Study dates
25 Mar 2024to Dec 2026
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
Show all 21Show fewer
  • 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.
  • For female patients of childbearing potential, have a negative pregnancy test documented ≤ 14 days prior to start of study medication.
  • 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
  • Signed written informed consent.

Who cannot join

  • 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.
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  • 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.
  • Have a known or suspected hypersensitivity to afatinib or its excipients.
  • Are pregnant, planning a pregnancy, or breastfeeding.
  • 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.
  • Previous allogeneic bone marrow transplant.
  • Have any condition or illness that, in the opinion of the investigator, would compromise patient safety or interfere with the study treatment.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kenneth Sooi contact

+65 6908 2222

kenneth_sooi@nuhs.edu.sg

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore

    Kenneth Sooi, +65 6908 2222, kenneth_sooi@nuhs.edu.sg

    Kenneth Sooi

    Recruiting

Other trials in Singapore

About this study

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

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.

Read the detailed description

This is a multi-center, open-label, phase II study of patients with stage IIIb-IV NSCLC harbouring EGFR PACC mutations.

Before taking the study drug, patients will need to undergo baseline assessments to ensure that they are eligible for the study. Then they will enter treatment period, where afatinib 40mg will be administered daily continuously, until the development of progressive disease or meeting discontinuation criteria. A discontinuation visit will be performed if patients stopped study drug for any reason. Thereafter, patients will be placed on Follow Up visit.

Clinical assessment, routine blood tests and routine imaging:

Physical examinations, imaging, and blood tests will be performed during baseline assessment, on the first day of each treatment cycle, after patients have completed the study and when clinically required by the treating physician. Patients will need to visit the doctor's office approximately 1-2 times every 4 weeks when they are receiving active treatment during the course of the study. More frequent visits may be needed as clinically indicated by the treating physician.

Treatment procedure:

Afatinib will be taken once a day at approximately the same time each day initially starting at a dose of 40mg. Afatinib must be taken on an empty stomach (at least one hour before or at least two hours after a meal).

Research Blood samples:

Blood samples for research will be taken at baseline, before starting cycle 3 and at the time of cancer progression. The estimated total volume of research blood that will be drawn is 10mL (2-3 teaspoons) each time for a total of 30mL.

Conditions
NSCLC
Being tested
Afatinib 40 MG
Keywords
Afatinib, PACC mutation, EGFR mutations

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Afatinib 40 MGDrug

    Also called Gilotrif

    Afatinib 40mg administered orally daily.

Study groups in NCT06062823
Study groupRoleWhat they receive
AfatinibExperimentalAfatinib given as monotherapy daily in a 28-days cycle.
Receives: Drug: Afatinib 40 MG

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

  1. Progression free survival

    Defined as the time from the date of study enrolment to the first date of documented disease progression

    Measured: 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)

  2. Overall survival

    Defined as the time from the date of randomisation until documented progression (according to RECIST v1.1) or death

    Measured: 48 months

  3. Duration of response

    Defined as the time from first documented Complete Response or Partial Response to the time of radiological progression or death, whichever occurs earlier.

    Measured: 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)

  4. Time to treatment failure

    Defined as the time from afatinib treatment to the time of treatment discontinuation for any reason including disease progression, treatment toxicity, and death

    Measured: 48 months

  5. Number of participant with treatment related toxicities

    Toxicities will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) toxicity grading Version 5

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Oct 2023
  2. Study start25 Mar 2024
  3. Primary completionOct 2026 (estimated)
  4. Study completionDec 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06062823
Sponsor's protocol ID
NS01/02/23
Status last verified
Jul 2025
First submitted
28 Aug 2023
Last updated
24 Jul 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815.

    PubMed 20087963

  • Mok TS, Wu YL, Thongprasert S, Yang CH, Chu DT, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang JJ, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009 Sep 3;361(10):947-57. doi: 10.1056/NEJMoa0810699. Epub 2009 Aug 19.

    PubMed 19692680

  • Planchard D, Smit EF, Groen HJM, Mazieres J, Besse B, Helland A, Giannone V, D'Amelio AM Jr, Zhang P, Mookerjee B, Johnson BE. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017 Oct;18(10):1307-1316. doi: 10.1016/S1470-2045(17)30679-4. Epub 2017 Sep 11.

    PubMed 28919011

  • Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010 Dec 15;127(12):2893-917. doi: 10.1002/ijc.25516.

    PubMed 21351269

  • Shaw AT, Ou SH, Bang YJ, Camidge DR, Solomon BJ, Salgia R, Riely GJ, Varella-Garcia M, Shapiro GI, Costa DB, Doebele RC, Le LP, Zheng Z, Tan W, Stephenson P, Shreeve SM, Tye LM, Christensen JG, Wilner KD, Clark JW, Iafrate AJ. Crizotinib in ROS1-rearranged non-small-cell lung cancer. N Engl J Med. 2014 Nov 20;371(21):1963-71. doi: 10.1056/NEJMoa1406766. Epub 2014 Sep 27.

    PubMed 25264305

  • Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, Iyer S, Reisman A, Wilner KD, Tursi J, Blackhall F; PROFILE 1014 Investigators. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014 Dec 4;371(23):2167-77. doi: 10.1056/NEJMoa1408440.

    PubMed 25470694

  • Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, Dechaphunkul A, Imamura F, Nogami N, Kurata T, Okamoto I, Zhou C, Cho BC, Cheng Y, Cho EK, Voon PJ, Planchard D, Su WC, Gray JE, Lee SM, Hodge R, Marotti M, Rukazenkov Y, Ramalingam SS; FLAURA Investigators. Osimertinib in Untreated EGFR-Mutated Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Jan 11;378(2):113-125. doi: 10.1056/NEJMoa1713137. Epub 2017 Nov 18.

    PubMed 29151359

  • Planchard D, Popat S, Kerr K, Novello S, Smit EF, Faivre-Finn C, Mok TS, Reck M, Van Schil PE, Hellmann MD, Peters S; ESMO Guidelines Committee. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1;29(Suppl 4):iv192-iv237. doi: 10.1093/annonc/mdy275. No abstract available.

    PubMed 30285222

  • Lynch TJ Jr, Kim ES, Eaby B, Garey J, West DP, Lacouture ME. Epidermal growth factor receptor inhibitor-associated cutaneous toxicities: an evolving paradigm in clinical management. Oncologist. 2007 May;12(5):610-21. doi: 10.1634/theoncologist.12-5-610.

    PubMed 17522250

  • Lacouture ME, Schadendorf D, Chu CY, Uttenreuther-Fischer M, Stammberger U, O'Brien D, Hauschild A. Dermatologic adverse events associated with afatinib: an oral ErbB family blocker. Expert Rev Anticancer Ther. 2013 Jun;13(6):721-8. doi: 10.1586/era.13.30. Epub 2013 Mar 18.

    PubMed 23506519

  • Aw DC, Tan EH, Chin TM, Lim HL, Lee HY, Soo RA. Management of epidermal growth factor receptor tyrosine kinase inhibitor-related cutaneous and gastrointestinal toxicities. Asia Pac J Clin Oncol. 2018 Feb;14(1):23-31. doi: 10.1111/ajco.12687. Epub 2017 May 2.

    PubMed 28464435

  • Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.

    PubMed 26051236

  • Robichaux JP, Le X, Vijayan RSK, Hicks JK, Heeke S, Elamin YY, Lin HY, Udagawa H, Skoulidis F, Tran H, Varghese S, He J, Zhang F, Nilsson MB, Hu L, Poteete A, Rinsurongkawong W, Zhang X, Ren C, Liu X, Hong L, Zhang J, Diao L, Madison R, Schrock AB, Saam J, Raymond V, Fang B, Wang J, Ha MJ, Cross JB, Gray JE, Heymach JV. Structure-based classification predicts drug response in EGFR-mutant NSCLC. Nature. 2021 Sep;597(7878):732-737. doi: 10.1038/s41586-021-03898-1. Epub 2021 Sep 15.

    PubMed 34526717

  • Russo A, Franchina T, Ricciardi G, Battaglia A, Picciotto M, Adamo V. Heterogeneous Responses to Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors (TKIs) in Patients with Uncommon EGFR Mutations: New Insights and Future Perspectives in this Complex Clinical Scenario. Int J Mol Sci. 2019 Mar 21;20(6):1431. doi: 10.3390/ijms20061431.

    PubMed 30901844

  • Kobayashi Y, Mitsudomi T. Not all epidermal growth factor receptor mutations in lung cancer are created equal: Perspectives for individualized treatment strategy. Cancer Sci. 2016 Sep;107(9):1179-86. doi: 10.1111/cas.12996. Epub 2016 Aug 9.

    PubMed 27323238

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Afatinib 40 MG in people with NSCLC, run by National University Hospital, Singapore at 1 site in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 24 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kenneth Sooi (+65 6908 2222, kenneth_sooi@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06062823, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2025.

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