Clinical Trial 23480

• Overview

  Study Title:

  A Phase 1/2 Study of a Selective FGFR2/3 Inhibitor, CGT4859, in Patients With Cholangiocarcinoma and Other Advanced Solid Tumors Harboring FGFR2 and/or FGFR3 Genetic Alterations

  Objective:

  Phase 1 (Escalation) Primary * To determine the maximum tolerated dose(s) (MTDs) or the maximum evaluated dose(s), dose-limiting toxicities (DLTs), and the recommended Phase 2 dose (RP2D) of CGT4859 in participants with iCCA and other FGFR2/3-altered advanced solid tumors Phase 1 (Escalation) Secondary * To evaluate the PK of CGT4859 in participants with iCCA and other FGFR2/3-altered advanced solid tumors * To evaluate the antitumor activity of CGT4859 in participants with iCCA and other FGFR2/3-altered advanced solid tumors Phase 2 (Signal Seeking) Primary * To evaluate the antitumor activity of CGT4859 at the RP2D in participants with iCCA and other FGFR2/3-altered advanced solid tumors Phase 2 (Signal Seeking) Secondary * To evaluate the antitumor activity of CGT4859 at the RP2D in participants with iCCA and other FGFR2/3-altered advanced solid tumors * To characterize the safety and tolerability of CGT4859 at the RP2D in participants with iCCA and other FGFR2/3-altered advanced solid tumors * To evaluate the PK of CGT4859 at the RP2D in participants with iCCA and other FGFR2/3-altered advanced solid tumors

• Treatments

  Therapies:

  Tyrosine Kinase Inhibitor

  Medications:

  CGT4859 ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Able to provide written informed consent.
  • Age ≥18 years at the time of informed consent.
  • Histologically confirmed locally advanced, metastatic, and/or unresectable iCCA or other solid tumor with documented FGFR2/3 alteration (ie, gene fusions, rearrangements, amplifications, overexpression, and short variants; refer to Section 13.5) in blood and/or tumor.
  • Previously treated with, not appropriate for, or declined standard-of-care first-line treatment.
  • Have at least one measurable lesion according to RECIST v1.1.
  • Able and willing to commit to study assessments and visit schedule.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
  • Resolution of toxicities from prior therapy to ≤Grade 1 (or baseline), including resolution of clinically significant laboratory abnormalities, before the first dose of study drug. Exceptions are alopecia, hypothyroidism, or type 1 diabetes mellitus controlled with medical intervention, and paronychia controlled with local intervention.
  • Have clinically acceptable local laboratory screening results within certain limits specified in the protocol.
  • Have an ejection fraction >50%.
  • For women of childbearing potential (defined as physiologically and anatomically capable of becoming pregnant), confirmation of a negative serum pregnancy test prior to dosing with study drug and agreement to the use of a highly effective method of contraception (Section 13.4) with or without a barrier contraception method (in accordance with country-specific guidance) during the study treatment period and for 6 months after the last dose of study drug; hormonal birth control should be supplemented with an effective barrier method. For male participants, agreement to use effective barrier contraception (ie, condoms) during the study treatment period and for 3 months after the last dose of study drug.
  • Additional criteria may apply.

• Exclusion Criteria

  Key Exclusion Criteria:
  • Treatment with any of the following anticancer therapies ≤5 half-lives of the parent drug and/or its active metabolite(s) or ≤14 days (whichever is shorter) before the first dose of study drug: FGFR inhibitors, Small molecule therapies, or Other investigational agents.
  • Treatment with chemotherapy or anti-cancer antibodies/other biological therapies within 21 days or 1 cycle, whichever is shorter, before the first dose of study drug.
  • Treatment with radiotherapy ≤2 weeks before the first dose of study drug.
  • Received >2 prior FGFRi therapies.
  • Received strong cytochrome P450 (CYP)3A4 inhibitors or inducers ≤14 days or ≤5 drug half-lives (whichever is longer) before the first dose of study drug, or the need to continue treatment with strong CYP3A4 inhibitors or inducers during the study.
  • Known hypersensitivity to components of CGT4859.
  • Clinically significant corneal disorders/keratopathy or retinal disorders including but not limited to bullous or band keratopathy, corneal abrasion/inflammation/ulceration, keratoconjunctivitis, diabetic retinopathy with macular edema, retinal vascular occlusion, confirmed by an ophthalmologic exam.
  • Current evidence of retinal detachment or history of FGFRi-induced retinal detachment associated with loss of visual acuity or history of eye disorder that led to discontinuation of FGFRi.
  • Clinically significant cardiac disease as defined by the protocol.
  • Major surgeries (eg, abdominal laparotomy) ≤4 weeks prior to the first dose of study drug.
  • Unable to swallow whole pills without being crushed or gastrointestinal abnormalities (eg, significant nausea and vomiting, malabsorption, external biliary shunt, or small bowel resection) that would preclude adequate absorption, metabolism, or excretion.
  • Any active bleeding excluding hemorrhoidal or gum bleeding.
  • Any other concurrent severe known disease or concurrent severe and/or uncontrolled medical condition (eg, uncontrolled diabetes, active uncontrolled infection, or clinically significant liver disease), either of which could compromise participation in the study.
  • Any psychosocial, familial, sociological, or geographical issue that could hamper compliance with the study protocol.
  • Seropositive for human immunodeficiency virus (HIV) 1 or 2 antibody, or positive for hepatitis B surface antigen, or hepatitis C virus (HCV) antibody. Participants with a positive HCV antibody may be eligible if HCV RNA is undetectable on a quantitative HCV RNA assay, following discussion with the Medical Monitor.
  • Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening.
  • Active, symptomatic, or untreated brain metastases unless the participant is clinically stable and off corticosteroids for ≥2 months.
  • Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment or expected to need treatment for an active malignancy. (The following are allowed within 3 years of study enrollment if the participant has received definitive local therapy [eg, surgical excision, external beam radiation, or other local therapy with curative intent]: non-melanoma skin cancers, localized prostate cancer, or carcinoma in situ.)
  • Any condition or issue that could hamper compliance with the study protocol in the judgment of the Investigator or Sponsor.
  • Pregnant or currently breastfeeding.
  • Additional criteria may apply.

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