Clinical Trials

Inclusion Criteria:

• Participant has provided written informed consent prior to initiation of any study-specific procedures.
• Men or women at least 18 years of age (or ≥ age of majority in local jurisdictions) at the time of signing the informed consent form (ICF).
• Histologically or cytologically confirmed diagnosis of advanced-stage malignancy, as follows:
  • Part A - Any type of advanced tumors harboring FGFR2 and/or FGFR3 gene alterations;
  • Part B Cohort 1 - Advanced ICC with FGFR2 gene alterations who previously demonstrated clinical benefit to FGFRi treatment and discontinued due to disease progression;
  • Part B Cohort 2 - Advanced UC with FGFR2 and/or FGFR3 gene alterations who previously demonstrated clinical benefit to FGFRi treatment and discontinued due to disease progression;
  • Part B Cohort 3 - Advanced ICC or UC with FGFR2 and/or FGFR3 gene alterations who are FGFRi naïve;
  • Part B Cohort 4 - Advanced solid tumors (other than ICC or UC) with FGFR2 and/or FGFR3 gene alterations who are FGFRi naïve or were previously treated with FGFRi.
• Participants must have either received prior standard of care therapy (including FGFRrelated agents approved in local jurisdictions) appropriate for their tumor type and stage of disease or, in the opinion of the Investigator, be unlikely to tolerate or to derive clinically meaningful benefit from standard of care therapy (applicable to Parts A & B).
• In Part B Cohorts 1 and 2, participants with ICC or UC driven by FGFR2 and/or FGFR3 gene alterations should have previously received an FGFR inhibitor, approved by the local regulatory agency or as an investigational agent within a clinical trial where such treatment exists (hereafter referred to as “such treatment”). Additionally, such treatment must have resulted in clinical benefit, for example objective tumor shrinkage (i.e., complete response [CR] or partial response [PR]) or sustained disease control (i.e., continuous stable disease for at least 8 weeks) prior to confirmed progressive disease. In Cohorts 3 and 4, FGFRi naïve participants must have received at least one line of prior systemic therapy. In Cohort 4, other solid tumors previously treated with FGFRi do not need to have demonstrated clinical benefit to such treatment.
• Participant’s tumor has documented FGFR2 and/or FGFR3 alteration in blood and/or tumor per local assessment as detected by DNA sequencing using a comprehensive nextgeneration sequencing assay (e.g., FoundationOne® CDx or Guardant360® CDx), breakapart fluorescence in situ hybridization (FISH), or other validated assay. Potential participants harboring an amplification as the only FGFR2 or 3 alteration would not be considered eligible. Genomic analysis of tumor tissue or circulating tumor-derived (blood) nucleic acids (ctDNA) must have been conducted in a Clinical Laboratory Improvement Amendments (CLIA)- certified laboratory (in US) or in accordance with local regulatory requirements (in other countries).
• Willing to provide an archived tumor tissue specimen (formalin-fixed paraffin embedded [FFPE] specimen) obtained within the last 5 years, if available.
• Willing to undergo pre-treatment tumor biopsy, if medically feasible. The availability of a FFPE tumor biopsy specimen obtained within 2 months prior to consent from participants who have not received intervening systemic anti-cancer therapy will satisfy the pretreatment biopsy requirement.
• Measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. For Part B, measurable disease only.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
• An estimated life expectancy of at least 3 months in the opinion of the Investigator.
• Adequate hematological lab assessments at screening, as follows:
  • Absolute neutrophil count (ANC) ≥ 1000/mm^3 (1.0 x 10^9 /L);
  • Platelet count ≥ 75,000/ mm^3 (75x 10^9 /L);
  • • Hemoglobin ≥ 9.0 g/dL (at least 7 days since most recent blood transfusion).
• Adequate renal laboratory assessments, as follows:
  • Estimated creatinine clearance ≥ 50 mL/min as calculated using the Cockcroft-Gault method or a method standard for the institution.
• Adequate hepatic laboratory assessments, as follows:
  • ALT and aspartate transaminase ≤ 3 x upper limit of normal (ULN), or ≤ 5 x ULN in the presence of liver metastases;
  • Serum total bilirubin ≤ 1.5 x ULN (< 3.0 x ULN for participants with documented Gilbert’s syndrome);
  • ALP ≤ 2.5 x ULN (≤ 5 x ULN in case of bone metastasis, biliary tract involvement or liver metastases).
• Adequate chemistry laboratory assessments, as follows:
  • Sodium ≥ 130 mEq/L or within institutional normal limits;
  • Potassium ≥ 3.6 mmol/L or within institutional normal limits;
  • Phosphate ≤ 1.5 x ULN.
• Able to swallow, retain, and absorb oral medications.

Exclusion Criteria:

- Known clinically-active or clinically-progressive brain metastases from non-brain tumors

- History and/or current evidence of abnormal calcium-phosphorous homeostasis, ectopic mineralization or calcification, or corneal or retinal disorder/keratopathy

- GI tract disease causing an inability to take oral medication, malabsorption syndrome, requirement for intravenous alimentation, or uncontrolled inflammatory GI disease

- Active, uncontrolled bacterial, fungal, or viral infection

- Women who are lactating or breastfeeding, or pregnant

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 10/9/23. Questions regarding updates should be directed to the study team contact.