Clinical Trials

Inclusion Criteria:

• Patient or legal representative is willing and able to provide written informed consent for the study prior to the performance of any study-specific procedures.
• Patient is ≥ 18 years of age.
• Patient must have disease that is refractory to standard therapy, disease that has not adequately responded to standard therapy, disease for which standard or curative therapy does not exist, or the patient must be intolerant to or have declined standard therapy.
• Patient must have measurable or evaluable disease per RECIST v1.1.
• Patient has ECOG PS of 0-2.

Exclusion Criteria:

• Patient’s cancer has a known primary driver alteration other than FGFR2 that is amenable to approved targeted therapy eg. EGFR, ALK, ROS, RET, PI3K, HER2, BRAF.
• Patient has history or ongoing, clinically significant corneal or retinal disorder.
• Patient has any of the following within 14 days prior to the first dose of RLY-4008:
  • Platelet count < 75 x 10^9 /L;
  • Absolute neutrophil count (ANC) < 1 x 10^9 /L;
  • Hemoglobin < 8 g/dL (red blood cell transfusion and erythropoietin may be used to reach 8 g/dL, but must have been administered at least 2 weeks prior to the first dose of RLY-4008);
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x the upper limit of normal (ULN) if no hepatic metastases are present; > 5 x ULN if hepatic metastases are present;
  • Total bilirubin > 1.5 x ULN; > 3 x ULN with direct bilirubin > 1.5 x ULN in presence of Gilbert’s disease;
  • Estimated (Cockcroft-Gault formula) or measured creatinine clearance < 50 mL/min.
• Patient has known active human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) and/or hepatitis C virus (HCV). Testing is not required.
• Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec. Patient has history of prolonged QT syndrome or Torsades de pointes. Patient has a familial history of prolonged QT syndrome.
• Patient has clinically significant, uncontrolled cardiovascular disease including congestive heart failure Grady III or IV according to the New York Heart Association (NYHA) classification; myocardial infarction or unstable angina within the previous six months, uncontrolled hypertension (Grade 3 or higher), or clinically significant, uncontrolled arrythmia, including bradyarrhythmias that may cause QT prolongation (e.g., Type II second degree heart block or third-degree heart block).
• Patient has CNS metastases or primary CNS tumor that is associated with progressive neurologic symptoms or requires increasing doses of corticosteroids to control the CNS disease. If patient requires corticosteroids for management of CNS disease, the dose must have been stable for the 2 weeks preceding C1D1. Patients with stable or asymptomatic CNS metastases or primary CNS can be eligible after consultation with the Sponsor.
• Patient received systemic antineoplastic therapy or radiotherapy within 14 days or 5 half-lives prior to the first dose of RLY-4008. RLY-4008 may be started within 5 days of 5 half-lives of prior therapy if considered by the Investigator to be safe and within the best interest of the patient – this must be approved by the Sponsor prior to dosing.
• Patient received local, hepatic therapy (e.g., transcatheter arterial chemoembolization [TACE] or yttrium90 [Y90]) within 4 weeks prior to C1D1.
• Patient received neutrophil growth factor support within 14 days of the first dose of RLY-4008.
• Patient requires treatment with a prohibited medication or use with caution herbal remedy that cannot be discontinued at least 2 weeks before the start of RLY4008 administration.
• Patient has had a major surgical procedure within 14 days of the first dose of RLY-4008 (procedures such as central venous catheter placement, tumor needle biopsy, and feeding
• tube placement are not considered major surgical procedures). Study centers should discuss other minor surgeries with the Medical Monitor.
• Patient has a history of another primary malignancy that has been diagnosed or required therapy within the past year. The following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, curatively treated localized thyroid cancer, and completely resected carcinoma in situ of any site.
• Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, or other study procedures and study restrictions.
• Women who are unwilling, if not postmenopausal or surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the RLY-4008 administration period and for at least 30 days after the last dose of RLY-4008. Men who are unwilling, if not surgically sterile, to abstain from sexual intercourse or employ highly effective contraception during the RLY-4008 administration period and for at least 90 days after the last dose of RLY-4008.
• Pregnant females, as documented by a serum beta human chorionic gonadotropin (β-hCG) pregnancy test consistent with pregnancy, obtained within 7 days prior to the first dose of RLY-4008. Females with β-hCG values that are within the range for pregnancy but are not pregnant (false-positives) may be enrolled with written consent of the Sponsor, after pregnancy has been ruled out. Females of non-childbearing potential (postmenopausal for more than 1 year; bilateral tubal ligation; bilateral oophorectomy; hysterectomy) do not require a serum β-hCG test.
• If female, patient is breastfeeding.
• Patient has prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the Investigator’s opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism, or excretion of the RLY-4008; or impair the assessment of study results.