Infigratinib in Subjects With GC or GEJ With FGFR2 Amplification or Other Solid Tumors With Other FGFR Alterations

NCT ID: NCT05019794

Last Updated: 2022-06-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-05-13

Study Completion Date

2023-12-30

Brief Summary

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Infigratinib is an oral drug which selectively binds to fibroblast growth factor receptor (FGFR) 1-3. This is a multicenter, open-label, single arm phase IIa study to evaluate the efficacy and safety of Infigratinib in subjects with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with FGFR2 genetic amplification or other advanced solid tumors with other FGFR genetic alternations who have failed in 2nd line or above treatment. This trial includes 2 cohorts (i.e., baskets) with above mentioned indications.

Detailed Description

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The subject will go through 4 periods, including Pre-screen period, screening period, treatment period and follow up period.

Pre-screening period (up to 28 days) For cohort 1, subject sign pre-screening ICF( Inform consent ), subject will do tumor biopsy or provide FFPE samples before prescreening for FGFR2-amp detection by FISH from the central laboratory. If the result is positive, subjects can go through the main screening stage, otherwise participants will be considered a prescreen failure. subjects can go through the main screening stage, otherwise participants will be considered a prescreen failure.

Screening period ( All cohorts; up to 28 days): Subjects who had positive genetic result could sign main ICF for all the screening examinations and establish study baseline documents. Only the eligible participants could enter the next treatment period.

Treatment period: Eligible subjects will be orally administered Infigratinib (125mg, QD) for 3 weeks on, 1-week off in each 28-day cycle until the occurrence of unacceptable toxicity, disease progression, withdrawing informed consent, death, contact lost, starting a new anticancer therapy, etc (whichever occurs first). During this period, subjects will be routinely assessed efficacy status by radiographic check at W9/W17/W25/W33 . After that, subjects will be evaluated every 12 weeks until disease progression. The safety assessment will be performed at cycle 1- 4;

Follow up period: Once a treatment discontinuation happens, subjects should return to the hospital within 30 days to receive a complete safety examination. Subjects with treatment discontinuation or disease progression should directly enter the follow-up period, visit approximately every 3 months for survival status reporting until withdrawing informed consent, death, contact lost, starting a new anti-cancer therapy, etc. (whichever occurs first).

Conditions

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Gastric Cancer Gastroesophageal Junction Adenocarcinoma Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ) with FGFR2 amplification

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off (every 4 weeks as one treatment cycle).

Group Type EXPERIMENTAL

Infigratinib

Intervention Type DRUG

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Advanced Solid tumors[Exclude GC/GEJ Arm and CHOL,UC]with FGFR1-3 fusions/rearrangements/mutations

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off (every 4 weeks as one treatment cycle).

Group Type EXPERIMENTAL

Infigratinib

Intervention Type DRUG

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Interventions

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Infigratinib

Infigratinib (BGJ398) 125 mg orally daily, 3 weeks on, 1 week off.

Intervention Type DRUG

Other Intervention Names

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BGJ398

Eligibility Criteria

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Inclusion Criteria

1. Cohort 1 : 1) histologically or cytologically confirmed locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. 2) failed 2nd line or above therapy with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma. 3) willing to do tumor biopsy for FGFR2 gene amplification via FISH test at central lab
2. Cohort 2: 1) Histologically or cytologically confirmed locally advanced or metastatic solid tumors other than CHOL and UC. 2) Subjects must have failed established standard medical anti-cancer therapies for a diagnosed tumor or have been intolerant to such therapy, or no standard therapy, or in the opinion of the Investigator have been considered ineligible for a particular form of standard therapy on medical grounds.(3) Previous documented proof of FGFR1, FGFR2 ,or FGFR3 fusions/rearrangements and activating mutations (FISH/NGS/PCR results could be accepted) presented by local laboratory or central laboratory. \[Except Cohort 1GC, or GEJ patients with FGFR2 amplification\]
3. Measurable disease by RECIST v1.1.
4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

Exclusion Criteria

To be eligible for the study, subjects must not meet any of the following criteria:

1. History of other primary malignancies within 3 years except adequately treated in situ carcinoma of the cervix or nonmelanoma carcinoma of the skin or any other curatively treated malignancy that is not expected to require treatment for recurrence during the course of the study.
2. Previous or current treatment of a mitogen-activated protein kinase (MAPK-MEK) or selective FGFR inhibitor.
3. Any known hypersensitivity to Infigratinib or its excipients.
4. Subjects with symptomatic central nervous system metastasis.
5. History and/or current evidence of extensive tissue calcification.
6. Amylase or lipase \>2.0 × ULN.
7. Abnormal calcium or phosphorus, or calcium-phosphorus product ≥55 mg2/dL2.
8. Current evidence of endocrine alterations of calcium/phosphate homeostasis.
9. Current evidence of corneal or retinal disorder/keratopathy.
10. Currently receiving or planning to receive treatment with agents or foods that are known strong inducers or inhibitors of CYP3A4 and medications which increase serum phosphorus and/or calcium concentration during this study. Subjects are not permitted to receive enzyme-inducing anti-epileptic drugs.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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LianBio LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Qiao Sun, Doctor

Role: STUDY_DIRECTOR

Shanghai LianBio Development Co., Ltd.

Locations

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Beijing Cancer Hospital ( Department of Thoracic Oncology )

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Cancer Hospital (Department of Gynecological Oncology)

Beijing, Beijing Municipality, China

Site Status RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Site Status RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, China

Site Status RECRUITING

Affiliated Hospital of Hebei University

Baoding, Hebei, China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status RECRUITING

Hubei Cancer Hospital

Wuan, Hubei, China

Site Status RECRUITING

The First People's Hospital of Changzhou

Changzhou, Jiangsu, China

Site Status RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, China

Site Status RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, China

Site Status RECRUITING

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, China

Site Status RECRUITING

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Sir Run Run Shaw hospital, Zhejiang University school of Medicine

Hangzhou, Zhejiang, China

Site Status RECRUITING

Henan Cancer Hospital

Henan, Zhengzhou, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Lei Mu, Master

Role: CONTACT

86 21 61329798

Facility Contacts

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Jun Zhao, Postdoctor

Role: primary

86 10 88196456

Yunong Gao, Master

Role: primary

86 10 88196448

Lin Shen

Role: primary

86 10 88196340

Chunmei Shi, Master

Role: primary

86 591 86218442

Jianwei Yang, Bachelor

Role: primary

86 591 83660063

Yanhong Deng

Role: primary

86 20 38254084

Aimin Zang, Master

Role: primary

86 312 5983056

Yanqiao Zhang, Postdoctor

Role: primary

86 451 86298220

Huiting Xu, Doctor

Role: primary

86 27 87671530

Haijiao Yan, Doctor

Role: primary

86 519 68871192

Jia Wei, Doctor

Role: primary

86 25 83106666

Jingdong Zhang, Postdoctor

Role: primary

86 24 31916392

Tianshu Liu, Doctor

Role: primary

86 21 64041990

Yusheng Wang, Doctor

Role: primary

86 351 4651509

Haiping Jiang, Doctor

Role: primary

86 571 87235657

Hongming Pan, Doctor

Role: primary

86 571 86006922

Ning Li, Doctor

Role: primary

86 371 56155233

References

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Hierro C, Alsina M, Sanchez M, Serra V, Rodon J, Tabernero J. Targeting the fibroblast growth factor receptor 2 in gastric cancer: promise or pitfall? Ann Oncol. 2017 Jun 1;28(6):1207-1216. doi: 10.1093/annonc/mdx081.

Reference Type BACKGROUND
PMID: 28327938 (View on PubMed)

Xue WJ, Li MT, Chen L, Sun LP, Li YY. Recent developments and advances of FGFR as a potential target in cancer. Future Med Chem. 2018 Sep 1;10(17):2109-2126. doi: 10.4155/fmc-2018-0103. Epub 2018 Aug 1.

Reference Type BACKGROUND
PMID: 30066580 (View on PubMed)

Dienstmann R, Rodon J, Prat A, Perez-Garcia J, Adamo B, Felip E, Cortes J, Iafrate AJ, Nuciforo P, Tabernero J. Genomic aberrations in the FGFR pathway: opportunities for targeted therapies in solid tumors. Ann Oncol. 2014 Mar;25(3):552-563. doi: 10.1093/annonc/mdt419. Epub 2013 Nov 20.

Reference Type BACKGROUND
PMID: 24265351 (View on PubMed)

Su X, Zhan P, Gavine PR, Morgan S, Womack C, Ni X, Shen D, Bang YJ, Im SA, Ho Kim W, Jung EJ, Grabsch HI, Kilgour E. FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study. Br J Cancer. 2014 Feb 18;110(4):967-75. doi: 10.1038/bjc.2013.802. Epub 2014 Jan 23.

Reference Type BACKGROUND
PMID: 24457912 (View on PubMed)

Zhang J, Tang PMK, Zhou Y, Cheng ASL, Yu J, Kang W, To KF. Targeting the Oncogenic FGF-FGFR Axis in Gastric Carcinogenesis. Cells. 2019 Jun 25;8(6):637. doi: 10.3390/cells8060637.

Reference Type BACKGROUND
PMID: 31242658 (View on PubMed)

Nogova L, Sequist LV, Perez Garcia JM, Andre F, Delord JP, Hidalgo M, Schellens JH, Cassier PA, Camidge DR, Schuler M, Vaishampayan U, Burris H, Tian GG, Campone M, Wainberg ZA, Lim WT, LoRusso P, Shapiro GI, Parker K, Chen X, Choudhury S, Ringeisen F, Graus-Porta D, Porter D, Isaacs R, Buettner R, Wolf J. Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I, Dose-Escalation and Dose-Expansion Study. J Clin Oncol. 2017 Jan 10;35(2):157-165. doi: 10.1200/JCO.2016.67.2048. Epub 2016 Nov 21.

Reference Type BACKGROUND
PMID: 27870574 (View on PubMed)

Related Links

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http://pubmed.ncbi.nlm.nih.gov/28327938/

To describe the FGFR2 plays a key role in gastric cancer pathogenesis. FGFR inhibitors have been tested in FGFR-aberrant GC patients. Efforts should be done to identify reliant predictive biomarkers for selecting patients most likely to benefit.

http://pubmed.ncbi.nlm.nih.gov/30066580/

To describe the basic knowledge regarding FGF/FGFR signaling and categorize the clinical FGFR inhibitors. The mechanisms of resistance to FGFR inhibitors and corresponding strategies of overcoming drug resistance will also be discussed.

http://pubmed.ncbi.nlm.nih.gov/24265351/

Strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors

http://pubmed.ncbi.nlm.nih.gov/31242658/

A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis.

http://pubmed.ncbi.nlm.nih.gov/31242658/

The pathogenic mechanisms of FGF-FGFR signaling in gastric adenocarcinoma together with the current targeted strategies in aberrant FGF-FGFR activated GC cases.

http://pubmed.ncbi.nlm.nih.gov/27870574/

Evaluation of BGJ398, a Fibroblast Growth Factor Receptor 1-3 Kinase Inhibitor, in Patients With Advanced Solid Tumors Harboring Genetic Alterations in Fibroblast Growth Factor Receptors: Results of a Global Phase I Stu

Other Identifiers

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LB1001-201

Identifier Type: -

Identifier Source: org_study_id

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