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

A Phase IIa of Infigratinib in Subjects With Locally Advanced or Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma With FGFR2 Amplification or Other Advanced Solid Tumors With Other FGFR Alterations

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.

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).

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.