Assessment of Anti-tumor and Safety in Glumetinib in Patients With c-MET-positive Non-Small Cell Lung Cancer

NCT04270591 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: SCC244-108
• Study Type: interventional
• Target: 183
• Locations: 3 countries
• Sites: 44

Brief Summary

Indication:Patients with Advanced c-MET-positive Non-Small Cell Lung Cancer Phase Ib (China only): Approximately 90 patients Phase Ⅱ (globally): Approximately 78 evaluable patients; addition of at least 6 patients in Safety Run-in (US only)

Conditions

C-Met Exon 14 Mutation

Keywords

MET; MET amplification; MET over-expression; C-Met Exon 14

Outcome Measures

Primary Outcomes (1)

• ORR

  ORR as determined by an Independent Radiology Review Committee (IRRC) according to RECIST Version 1.1.

  through study completion, an average of 1 year

Secondary Outcomes (3)

• ORR(assessed as per investigators)

  through study completion, an average of 1 year

• DOR

  The time from the date of first documented partial response or complete response to progressive disease or death, an average of 6 months

• Efficacy of glumetinib

  Through study completion, an average of 1 year.

Study Arms (1)

SCC244 300mg

OTHER

Phase Ib: SCC244 300mg, QD Phase II: SCC244 300mg, QD

Drug: Glumetinib

Interventions

Glumetinib DRUG

The investigational product will be orally administrated when fasting at dose level of 300mg QD

Also known as: SCC244

SCC244 300mg

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide informed consent voluntarily.
• Male and female patients ≥ 18 years of age (or having reached the age of majority according to local laws and regulations, if the age is \> 18 years).
• Histologically or cytologically confirmed diagnosis of NSCLC including PSC.
• Patients with stage IIIb or IIIc NSCLC who are not candidates for definitive surgical resection or concurrent chemoradiation or patients with stage IV NSCLC (AJCC version 8).
• For Phase Ib study, patients should carry at least one of the following MET alterations (by local or Sponsor-designated central laboratory screening):
• METex14 skipping mutation who had previously treated by other MET inhibitor(s) or
• METex14 skipping mutation who had received 3 or more lines prior systemic therapies without MET inhibitor for the advanced NSCLC or
• MET amplification GCN ≥ 4 or MET/CEP7 ratio ≥ 2) or
• MET over-expression (IHC2+).
• For Phase II study, patients with METex14 skipping mutation in tumor or ctDNA samples (local testing is acceptable for eligibility, however if the results of the central laboratory is available, the report of the central laboratory shall prevail); all patients in Phase II study will have confirmation of METex14 skipping mutation by Sponsor-designated central laboratory but this result is not necessary for eligibility.
• Availability of tumor tissue sample (either fresh tumor biopsy or archival tumor tissue sample); for patients of phase II study (not mandatory for safety run-in), if screened and enrolled based on local test results of METex14 skipping, the tumor tissue sample must be available for central laboratory testing before C2D1; if local testing results meet the requirements, patients of phase Ib are exempt from the central laboratory confirm.
• For Phase II study, patients are not eligible for chemotherapy or refuse chemotherapy after well-informed or have failed one or two prior lines of systemic therapies for the advanced NSCLC.
• Treatment failure is defined as documented disease progression or intolerance to treatment.
• Maintenance therapy given after first line chemotherapy will be considered as part of the first line if given to patients with documented response or stable disease before starting the maintenance therapy.
• Prior neoadjuvant/adjuvant systematic therapies will count as one prior line of treatment, provided that disease recurred within 12 months of completion of neoadjuvant/adjuvant therapy.

You may not qualify if:

• Patients who meet any of the following criteria shall be excluded from the study:
• Patients with targetable activating EGFR mutation, ALK rearrangement, ROS1 rearrangement, BRAF mutation or NTRK fusion that have available standard of care therapies.
• Patients who have symptomatic CNS metastasis which is neurologically unstable or those who have CNS disease requiring increase in the dose of steroid. (Note: Patients with controlled CNS metastasis can participate in the trial. Before entering the study, patients should have finished radiotherapy, or have received operation for CNS tumor metastasis at least two weeks before. Patients' neurological function must be in a stable state; no new neurological deficit is found during clinical examination and no new problem is found during CNS imaging examinations. If patients need to use steroids to treat CNS metastasis, the therapeutic dose of steroid should be stable for ≥ 3 months at least two weeks prior to entering the study with treatment dose no more than dexamethasone 4 mg daily or an equivalent dose of steroids.)
• Prior exposure to MET-directed therapy (except patients harboring METex14 skipping in Phase Ib study).
• Evidence of past or current primary malignancies other than NSCLC (except for non-melanoma skin cancer, in situ breast cancer or in situ cervical carcinoma and superficial bladder cancer, or other cancer curatively treated and with no evidence of disease for at least 5 years).
• Subjects with clinically significant cardiovascular disease, including:
• NYHA Class III or higher congestive heart failure;
• History or current evidence of serious uncontrolled ventricular arrhythmias requiring drug therapy;
• Acute myocardial infarction, severe or unstable angina pectoris, coronary artery or peripheral artery bypass graft received within 6 months prior to the first dose;
• Left ventricular ejection fraction (LVEF) \< 50%;
• Fridericia's corrected QT interval (QTcF) \> 460 ms on ECG conducted during screening;
• Congenital long QT syndrome, or any known history of torsade de pointes (TdP), or family history of unexplained sudden death;
• Clinically uncontrolled hypertension (after standard antihypertensive treatment, systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg);
• Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2 prior neuropathy.
• Known HIV infection with a history of acquired immunodeficiency syndrome (AIDS)-defining opportunity infection within the past 12 months; active hepatitis B and hepatitis C. Patients whose test results meet one of the following will not be enrolled:

Sponsors & Collaborators

• Haihe Biopharma Co., Ltd.: lead

Study Sites (44)

Norton Cancer Institute

Louisville, Kentucky, 40233, United States

NOT YET RECRUITING

The Oncology Institute of Hope & Innovation

Louisville, Kentucky, 40233, United States

RECRUITING

Anhui Province Hospital

Hefei, Anhui, 230000, China

RECRUITING

The Chest Hospital of Anhui Province

Hefei, Anhui, 230000, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Beijing Cancer Hospita

Beijing, Beijing Municipality, 100000, China

RECRUITING

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

Union Medical College Hospital Affiliated to Fujian Medical University

Fuzhou, Fujian, 350000, China

RECRUITING

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510000, China

RECRUITING

Cancer Hospital Affiliated to Guangxi Medical University

Nanning, Guangxi, 530000, China

RECRUITING

Hainan Cancer Hospital

Haikou, Hainan, 570000, China

RECRUITING

Cancer Hospital Affiliated to Harbin Medical University

Harbin, Heilongjiang, 150000, China

RECRUITING

Henan Province Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Hubei Cancer Hospital

Wuhan, Hubei, 430000, China

RECRUITING

Wuhan Union Hospital

Wuhan, Hubei, 430000, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410000, China

RECRUITING

Jiangsu Cancer Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

Jiangsu Province People's Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330000, China

RECRUITING

First Hospital of Jilin University

Changchun, Jilin, 130000, China

RECRUITING

Liaoning Cancer Hospital

Shenyang, Liaoning, 110000, China

RECRUITING

Affiliated Hospital of Hebei University

Baoding, Shandong, 071000, China

RECRUITING

Shandong University Qilu Hospital

Jinan, Shandong, 250000, China

RECRUITING

Changhai Hospital

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

Fudan university Shanghai cancer center

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

The Chest Hospital of Shanghai

Shanghai, Shanghai Municipality, 200000, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

RECRUITING

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300000, China

RECRUITING

The First Affiliated Hospital，College of of Medicine, Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

Zhejiang Province Cancer Hospital

Hangzhou, Zhejiang, 310000, China

RECRUITING

Hunan Province Cancer Hospital

Changsha, 410000, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, 450000, China

RECRUITING

Ehime University Hospital

Ehime, Japan

RECRUITING

Kyushu University Hospital

Fukuoka, Japan

RECRUITING

Kanagawa Cancer Center

Kanagawa, Japan

RECRUITING

Niigata Cancer Center Hospital

Niigata, Japan

RECRUITING

Kindai University Hospital

Osaka, Japan

RECRUITING

Osaka International Cancer Institute

Osaka, Japan

RECRUITING

Hokkaido University Hospital

Sapporo, Japan

RECRUITING

Shizuoka Cancer Center

Shizuoka, Japan

RECRUITING

National Cancer Center Hospital East

Tokyo, Japan

RECRUITING

National Cancer center

Tokyo, Japan

RECRUITING

Tottori University Hospital

Tottori, Japan

RECRUITING

Related Publications (13)

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  BACKGROUND

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  BACKGROUND

• Yin L, Lu Y. [MET Exon 14 Skipping Mutations in Non-small Cell Lung Cancer]. Zhongguo Fei Ai Za Zhi. 2018 Jul 20;21(7):553-559. doi: 10.3779/j.issn.1009-3419.2018.07.09. Chinese.

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• Vuong HG, Ho ATN, Altibi AMA, Nakazawa T, Katoh R, Kondo T. Clinicopathological implications of MET exon 14 mutations in non-small cell lung cancer - A systematic review and meta-analysis. Lung Cancer. 2018 Sep;123:76-82. doi: 10.1016/j.lungcan.2018.07.006. Epub 2018 Jul 6.

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• Liu SY, Gou LY, Li AN, Lou NN, Gao HF, Su J, Yang JJ, Zhang XC, Shao Y, Dong ZY, Zhou Q, Zhong WZ, Wu YL. The Unique Characteristics of MET Exon 14 Mutation in Chinese Patients with NSCLC. J Thorac Oncol. 2016 Sep;11(9):1503-10. doi: 10.1016/j.jtho.2016.05.016. Epub 2016 May 30.

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• Frampton GM, Ali SM, Rosenzweig M, Chmielecki J, Lu X, Bauer TM, Akimov M, Bufill JA, Lee C, Jentz D, Hoover R, Ou SH, Salgia R, Brennan T, Chalmers ZR, Jaeger S, Huang A, Elvin JA, Erlich R, Fichtenholtz A, Gowen KA, Greenbowe J, Johnson A, Khaira D, McMahon C, Sanford EM, Roels S, White J, Greshock J, Schlegel R, Lipson D, Yelensky R, Morosini D, Ross JS, Collisson E, Peters M, Stephens PJ, Miller VA. Activation of MET via diverse exon 14 splicing alterations occurs in multiple tumor types and confers clinical sensitivity to MET inhibitors. Cancer Discov. 2015 Aug;5(8):850-9. doi: 10.1158/2159-8290.CD-15-0285. Epub 2015 May 13.

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• Lu S, Yu Y, Zhou J, Li X, Goto K, Min X, Nishino K, Cui J, Wu L, Sakakibara J, Shu Y, Dong X, Li L, Yoneshima Y, Zhou C, Li X, Zhang Y, Huang D, Zang A, Zhang W, Wang X, Zhang L, Bai C, Fang J, Cao L, Zhao Y, Yu Y, Shi M, Zhong D, Li F, Duanmu W, Wang Y. Long-term follow-up results from the GLORY study: phase II study of gumarontinib in East Asian patients with MET exon 14 skipping mutated non-small cell lung cancer. Transl Lung Cancer Res. 2025 Sep 30;14(9):3924-3938. doi: 10.21037/tlcr-2025-638. Epub 2025 Sep 28.

  PMID: 41132955 DERIVED

• Yu Y, Dong W, Shi Y, Wu R, Yu Q, Ye F, Zhou C, Dong X, Li X, Li Y, Li Z, Wu L, Pan Y, Shen H, Wu D, Xu Z, Wu J, Xu N, Qin Y, Zang A, Zhang J, Zhou J, Zhang X, Zhao Y, Li F, Wang H, Liu Q, Han Z, Li J, Lu S. A pooled analysis of clinical outcome in driver-gene negative non-small cell lung cancer patients with MET overexpression treated with gumarontinib. Ther Adv Med Oncol. 2024 Jul 31;16:17588359241264730. doi: 10.1177/17588359241264730. eCollection 2024.

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MeSH Terms

Interventions

glumetinib

Study Officials

• James Zhou, MD

  Haihe Biopharma

  STUDY DIRECTOR

Central Study Contacts

Shun LU, Doctor

CONTACT

+86-21-22200000ext2153; shun_lu@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase Ib：300 mg QD Glumetinib Phase II：300 mg QD Glumetinib

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: February 17, 2020
• Study Start: July 15, 2019
• Primary Completion: October 25, 2023
• Study Completion: December 30, 2023
• Last Updated: August 1, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (31); JP (11); US (2)