IRB Study Number 24-1189
Status Recruiting
Institute Taussig Cancer Institute
Description
Phase 1: Dose Escalation
Primary Objectives
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
Secondary Objectives
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 Objectives
To evaluate the antitumor activity of CGT4859 at the RP2D in participants with iCCA and other FGFR2/3-altered advanced solid tumors
Secondary Objectives
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
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 (refer to Exclusion Criteria #1 and #2 for restrictions)
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 (Section 13.10)
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 below:
• Absolute neutrophil count ≥1×109/L
• Hemoglobin ≥9 g/dL
• Platelet count ≥75×109/L
• International normalized ratio (INR) <1.5 (or <3.0 for participants on anticoagulants)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3×upper limit of normal (ULN) or ≤5×ULN in the presence of hepatic metastases
• Total bilirubin ≤1.5×ULN; for participants with confirmed Gilbert’s syndrome, total bilirubin >1.5×ULN is acceptable provided direct bilirubin ≤1.5×ULN and indirect bilirubin ≤3×ULN
• Creatinine clearance ≥60 mL/min according to the Cockcroft-Gault equation
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
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
• 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 (Section 13.7)
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, defined by any of the following:
• Clinically significant cardiac arrhythmias and/or the need for antiarrhythmic therapy (excluding beta blockers or digoxin). (Participants with controlled atrial fibrillation are not excluded.)
• Congenital long QT syndrome, ≥Grade 3 hypokalemia, or use of concomitant medications known to prolong the QT interval, as defined in Section 13.8
• A marked baseline prolongation of QT/corrected QT (QTc) interval (eg, repeated demonstration of a QTc interval >470 milliseconds [ms] using Fridericia’s QT correction formula)
• Clinically significant history of cardiac disease or congestive heart failure >New York Heart Association Class II. Participants must not have unstable angina (anginal symptoms at rest) or new onset angina within 3 months or myocardial infarction within 6 months prior to enrollment.
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the 6 months before study drug initiation (except for adequately treated catheter-related venous thrombosis or incidental asymptomatic thrombotic events occurring more than 1 month before the first dose of study drug)
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
NOTE: Oral antibiotics for a controlled infection are permitted. Participants on antimicrobial, antifungal, or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met
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
