Neoadjuvant Lazertinib Therapy in EGFR-Mutation Positive Lung Adenocarcinoma Detected by BALF Liquid Biopsy

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II, Single-Center, Single-Arm, Prospective Study of Neoadjuvant Lazertinib Therapy in Resectable EGFR-Mutation Positive Lung Adenocarcinoma Patients Detected by Broncho-alveolar Lavage Fluid(BALF) Liquid Biopsy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05469022
• Other study ID #: NeolazBAL
• Status: Recruiting
• Phase: Phase 2
• Start date: May 19, 2022
• Est. completion date: May 19, 2027

Study information

• Verified date: July 2022
• Source: Konkuk University Medical Center
• Contact: In Ae Kim, MD. PhD.
• Phone: +821035438353
• Email: 20180618[@]kuh.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Complete surgical resection is the standard treatment in early-stage lung cancer. However, the patients with early resected Epidermal Growth Factor Receptor(EGFR)-mutated lung cancers have high recurrence rate. The efficacy of neoadjuvant treatment by first-generation EGFR-Tyrosine Kinase Inhibitor(TKI) has been demonstrated, however, that of the third-generation EGFR-TKI(lazertinib) has not yet been fully investigated. The aim of this study is to evaluate the efficacy of neoadjuvant Lazertinib in resectable EGFR mutation-positive NSCLC and clinical application of extracellular vesicles(EVs) based BALF liquid biopsy to identify EGFR mutation without invasive tissue biopsy.

Description:

The neoadjuvant treatment of 3rd-generation EGFR-TKI, lazertinib for 9 weeks before surgery is administrated. After the surgery, the patients with the tumor over stage 2 are given the lazertinib to prevent recurrence for 3 years or until recurrence. In early lung cancer, a tissue biopsy is often difficult due to the small size or the risky location. We collect bronchoalveolar lavage fluid for liquid biopsy and lazertinib is administrated according to the result of BALF liquid EGFR genotyping.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: May 19, 2027
• Est. primary completion date: May 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria:

1. Age = 19 years

2. Patients with suspected lung cancer on chest CT findings

3. Patients with the following EGFR gene mutations in the test on bronchoalveolar lavage fluid: E19Del, L858R alone or concurrent rare EGFR gene mutations (T790M, G719X, exon 20 insertion, S768I)

4. Patients whose tumor can be completely resected by surgery: patients with stage I-IIIB, or stage IVA who has single metastasis

5. Patients not previously treated with EGFR-TKIs such as gefitinib, erlotinib, afatinib, dacomitinib

6. Patients with the measurable lesion of 1 cm or more according to RECIST v1.1

7. Eastern Cooperative Oncology Group (ECOG) 0-1

8. EGFR-TKIs (gefitinib, erlotinib, afatinib,dacomitinib) naive patients

9. Patients with adequate pulmonary and heart function for surgery

10. Adequate organ function defined as Hemoglobin = 9.0g/dL Absolute neutrophil count = 1500/mm3 Platelet = 100,000 /mm3 Serum creatinine= normal range*1.5x Aminotransferase/Alkaline phosphatase =normal range*2.5x Total bilirubin =1.5 mg/dL Liver metastasis: Aminotransferase/Alkaline phosphatase = normal range* 5x Bone metastasis Alkaline phosphatase = normal range* 5x

11. Female patients with childbearing potential should be using adequate contraceptive measures. Female patients must have evidence of non-child-bearing potential(Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments)

12. Men with a female partner of childbearing potential must have either had a prior vasectomy or agree to use effective contraception for at least 14 days prior to administration of the first dose of study treatment, during the study, and for 3 months following the last dose of Lazertinib.

Exclusion Criteria:

1. Uncontrolled active interstitial lung disease

2. Pathologically confirmed N3 disease

3. Uncontrolled stage III-IV other malignancy

4. Uncontrolled Hypertension, Congestive Heart failure with New York Heart Association(NYHA) = 3, acute myocardial infarct history within 6 months before screening. 2nd- 3rd Atrio-Ventricular(AV) block or complete AV block

5. Gastrointestinal diseases (e.g. Chron's disease, ulcerative colitis) or malabsorption syndrome that would impact on drug absorption

6. Active infection requiring ongoing treatment(e.g. active Hepatitis B virus, Hepatitis C virus or Human immunodeficiency virus)

7. History of hypersensitivity to active or inactive excipients of Lazertinib or drugs with a similar chemical structure.

8. No ability to comply with protocol requirements.

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of Lung
• Non Small Cell Lung Cancer

Intervention

Drug:
• Neoadjuvant lazertinib
Lazertinib 240mg p.o once daily.

Locations

Country	Name	City	State
Korea, Republic of	Konkuk University Medical Center	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Konkuk University Medical Center	Yuhan Corporation

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (14)

Ahn MJ, Han JY, Lee KH, Kim SW, Kim DW, Lee YG, Cho EK, Kim JH, Lee GW, Lee JS, Min YJ, Kim JS, Lee SS, Kim HR, Hong MH, Ahn JS, Sun JM, Kim HT, Lee DH, Kim S, Cho BC. Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study. Lancet Oncol. 2019 Dec;20(12):1681-1690. doi: 10.1016/S1470-2045(19)30504-2. Epub 2019 Oct 3. Erratum in: Lancet Oncol. 2020 Feb;21(2):e70. — View Citation

Hur JY, Lee JS, Kim IA, Kim HJ, Kim WS, Lee KY. Extracellular vesicle-based EGFR genotyping in bronchoalveolar lavage fluid from treatment-naive non-small cell lung cancer patients. Transl Lung Cancer Res. 2019 Dec;8(6):1051-1060. doi: 10.21037/tlcr.2019.12.16. — View Citation

Kim IA, Hur JY, Kim HJ, Kim WS, Lee KY. Extracellular Vesicle-Based Bronchoalveolar Lavage Fluid Liquid Biopsy for EGFR Mutation Testing in Advanced Non-Squamous NSCLC. Cancers (Basel). 2022 May 31;14(11). pii: 2744. doi: 10.3390/cancers14112744. — View Citation

Kim IA, Hur JY, Kim HJ, Lee SE, Kim WS, Lee KY. Liquid biopsy using extracellular vesicle-derived DNA in lung adenocarcinoma. J Pathol Transl Med. 2020 Nov;54(6):453-461. doi: 10.4132/jptm.2020.08.13. Epub 2020 Oct 8. Review. — View Citation

Liu SY, Zhang JT, Zeng KH, Wu YL. Perioperative targeted therapy for oncogene-driven NSCLC. Lung Cancer. 2022 May 21. pii: S0169-5002(22)00437-8. doi: 10.1016/j.lungcan.2022.05.007. [Epub ahead of print] Review. — View Citation

Pennell NA, Neal JW, Chaft JE, Azzoli CG, Jänne PA, Govindan R, Evans TL, Costa DB, Wakelee HA, Heist RS, Shapiro MA, Muzikansky A, Murthy S, Lanuti M, Rusch VW, Kris MG, Sequist LV. SELECT: A Phase II Trial of Adjuvant Erlotinib in Patients With Resected Epidermal Growth Factor Receptor-Mutant Non-Small-Cell Lung Cancer. J Clin Oncol. 2019 Jan 10;37(2):97-104. doi: 10.1200/JCO.18.00131. Epub 2018 Nov 16. Erratum in: J Clin Oncol. 2019 Mar 1;37(7):612. — View Citation

Schaake EE, Kappers I, Codrington HE, Valdés Olmos RA, Teertstra HJ, van Pel R, Burgers JA, van Tinteren H, Klomp HM. Tumor response and toxicity of neoadjuvant erlotinib in patients with early-stage non-small-cell lung cancer. J Clin Oncol. 2012 Aug 1;30(22):2731-8. doi: 10.1200/JCO.2011.39.4882. Epub 2012 Jul 2. — View Citation

Xie H, Wang H, Xu L, Li M, Peng Y, Cai X, Feng Z, Ren W, Peng Z. Gefitinib Versus Adjuvant Chemotherapy in Patients With Stage II-IIIA Non-Small-Cell Lung Cancer Harboring Positive EGFR Mutations: A Single-Center Retrospective Study. Clin Lung Cancer. 2018 Nov;19(6):484-492. doi: 10.1016/j.cllc.2018.05.007. Epub 2018 May 26. — View Citation

Xiong L, Li R, Sun J, Lou Y, Zhang W, Bai H, Wang H, Shen J, Jing B, Shi C, Zhong H, Gu A, Jiang L, Shi J, Fang W, Zhao H, Zhang J, Wang J, Ye J, Han B. Erlotinib as Neoadjuvant Therapy in Stage IIIA (N2) EGFR Mutation-Positive Non-Small Cell Lung Cancer: A Prospective, Single-Arm, Phase II Study. Oncologist. 2019 Feb;24(2):157-e64. doi: 10.1634/theoncologist.2018-0120. Epub 2018 Aug 29. — View Citation

Yue D, Xu S, Wang Q, Li X, Shen Y, Zhao H, Chen C, Mao W, Liu W, Liu J, Zhang L, Ma H, Li Q, Yang Y, Liu Y, Chen H, Wang C. Erlotinib versus vinorelbine plus cisplatin as adjuvant therapy in Chinese patients with stage IIIA EGFR mutation-positive non-small-cell lung cancer (EVAN): a randomised, open-label, phase 2 trial. Lancet Respir Med. 2018 Nov;6(11):863-873. doi: 10.1016/S2213-2600(18)30277-7. Epub 2018 Aug 24. — View Citation

Zhang Y, Fu F, Hu H, Wang S, Li Y, Hu H, Chen H. Gefitinib as neoadjuvant therapy for resectable stage II-IIIA non-small cell lung cancer: A phase II study. J Thorac Cardiovasc Surg. 2021 Feb;161(2):434-442.e2. doi: 10.1016/j.jtcvs.2020.02.131. Epub 2020 Mar 19. — View Citation

Zhong W, Yang X, Yan H, Zhang X, Su J, Chen Z, Liao R, Nie Q, Dong S, Zhou Q, Yang J, Tu H, Wu YL. Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status. J Hematol Oncol. 2015 May 17;8:54. doi: 10.1186/s13045-015-0151-3. — View Citation

Zhong WZ, Chen KN, Chen C, Gu CD, Wang J, Yang XN, Mao WM, Wang Q, Qiao GB, Cheng Y, Xu L, Wang CL, Chen MW, Kang X, Yan W, Yan HH, Liao RQ, Yang JJ, Zhang XC, Zhou Q, Wu YL. Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study. J Clin Oncol. 2019 Sep 1;37(25):2235-2245. doi: 10.1200/JCO.19.00075. Epub 2019 Jun 13. — View Citation

Zhong WZ, Wang Q, Mao WM, Xu ST, Wu L, Shen Y, Liu YY, Chen C, Cheng Y, Xu L, Wang J, Fei K, Li XF, Li J, Huang C, Liu ZD, Xu S, Chen KN, Xu SD, Liu LX, Yu P, Wang BH, Ma HT, Yan HH, Yang XN, Zhou Q, Wu YL; ADJUVANT investigators. Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study. Lancet Oncol. 2018 Jan;19(1):139-148. doi: 10.1016/S1470-2045(17)30729-5. Epub 2017 Nov 21. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate	The objective response rate (ORR) evaluated with RECIST version 1.1. It is defined as the proportion of patients with complete response (CR) or partial response (PR) after 9 weeks of lazertinib administration	9 weeks after the starting day of the lazertinib
Secondary	Down-staging rate	The rate of downstage by pathology stage compared with clinical stage	From the day of screening to an average of 16 weeks after the first dose
Secondary	Major pathological response	The proportion of patients with less than 10% of the cancer cells in the surgical sample.	From the day of screening to an average of 16 weeks after the first dose
Secondary	Disease-free survival rate	The length of time after surgical resection the patient remains free of recurrence/progression or death, whatever the cause.	up to 3 years after surgery
Secondary	The concordance rate of EGFR mutations between surgical tissue and BAL fluid samples	The concordance rate of BALF EGFR mutation compared with EGFR mutation status of surgical resected tissue	From the day of screening day to an average of 16 weeks after the first dose