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

NCT05019794 | Unknown Phase 2

• 1 other identifier: LB1001-201
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 17

Brief Summary

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.

Conditions

Gastric Cancer; Gastroesophageal Junction Adenocarcinoma; Solid Tumor

Keywords

Gastric Cancer; Receptors, Fibroblast Growth Factor; Gastroesophageal Junction; Solid tumor

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Defined as the proportion of subjects with confirmed responses of CR or PR; Tumor response status will be assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  Approximately 12 months after dosed

Secondary Outcomes (13)

• Duration of response (DOR)

  Approximately 12 months after dosed

• Disease Control Rate (DCR)

  Approximately 12 months after dosed

• Best Overall Response (BOR)

  Approximately 12 months after dosed

• Progression-free survival (PFS)

  Approximately 12 months after dosed

• Overall Survival (OS)

  Approximately 24 months after dosed

Study Arms (2)

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

EXPERIMENTAL

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

Drug: Infigratinib

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

EXPERIMENTAL

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

Drug: Infigratinib

Interventions

Infigratinib DRUG

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

Also known as: BGJ398

Advanced Solid tumors[Exclude GC/GEJ Arm and CHOL,UC]with FGFR1-3 fusions/rearrangements/mutations; Gastric cancer (GC) or gastroesophageal junction adenocarcinoma (GEJ) with FGFR2 amplification

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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. \[Except Cohort 1GC, or GEJ patients with FGFR2 amplification\]
• Measurable disease by RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

You may not qualify if:

• To be eligible for the study, subjects must not meet any of the following criteria:
• 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.
• Previous or current treatment of a mitogen-activated protein kinase (MAPK-MEK) or selective FGFR inhibitor.
• Any known hypersensitivity to Infigratinib or its excipients.
• Subjects with symptomatic central nervous system metastasis.
• History and/or current evidence of extensive tissue calcification.
• Amylase or lipase \>2.0 × ULN.
• Abnormal calcium or phosphorus, or calcium-phosphorus product ≥55 mg2/dL2.
• Current evidence of endocrine alterations of calcium/phosphate homeostasis.
• Current evidence of corneal or retinal disorder/keratopathy.
• 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.

Sponsors & Collaborators

• LianBio LLC: lead

Study Sites (17)

Beijing Cancer Hospital ( Department of Thoracic Oncology )

Beijing, Beijing Municipality, 100142, China

RECRUITING

Beijing Cancer Hospital (Department of Gynecological Oncology)

Beijing, Beijing Municipality, 100142, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

RECRUITING

The Sixth Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

Affiliated Hospital of Hebei University

Baoding, Hebei, 071030, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

RECRUITING

Hubei Cancer Hospital

Wuan, Hubei, 430079, China

RECRUITING

The First People's Hospital of Changzhou

Changzhou, Jiangsu, 213004, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Liaoning Cancer Hospital & Institute

Shenyang, Liaoning, 110042, China

RECRUITING

Zhongshan Hospital Fudan University

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

Shanxi Provincial Cancer Hospital

Taiyuan, Shanxi, 030013, China

RECRUITING

The First Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

RECRUITING

Sir Run Run Shaw hospital, Zhejiang University school of Medicine

Hangzhou, Zhejiang, 310016, China

RECRUITING

Henan Cancer Hospital

Henan, Zhengzhou, 450008, China

RECRUITING

Related Publications (6)

• 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.

  PMID: 28327938 BACKGROUND

• 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.

  PMID: 30066580 BACKGROUND

• 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.

  PMID: 24265351 BACKGROUND

• 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.

  PMID: 24457912 BACKGROUND

• 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.

  PMID: 31242658 BACKGROUND

• 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.

  PMID: 27870574 BACKGROUND

Related Links

• 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.
• 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.
• Strengthening the role of FGFR signaling in cancer biology and providing more possibilities for the therapeutic application of FGFR inhibitors
• A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis.
• The pathogenic mechanisms of FGF-FGFR signaling in gastric adenocarcinoma together with the current targeted strategies in aberrant FGF-FGFR activated GC cases.
• 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

MeSH Terms

Conditions

Stomach Neoplasms; Acrocephalosyndactylia

Interventions

infigratinib

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Craniosynostoses; Synostosis; Dysostoses; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Syndactyly; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Limb Deformities, Congenital; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Qiao Sun, Doctor

  Shanghai LianBio Development Co., Ltd.

  STUDY DIRECTOR

Central Study Contacts

Lei Mu, Master

CONTACT

86 21 61329798; Lei.mu@lianbio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2021
• First Posted: August 25, 2021
• Study Start: May 13, 2020
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2023
• Last Updated: June 27, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (17)