NL-OMON54283招募中不适用
A First-in-Human Study of Highly Selective FGFR2 Inhibitor, RLY-4008, in Patients With Intrahepatic Cholangiocarcinoma (ICC) and Other Advanced Solid Tumors - RLY-4008-101
适应症
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •General Inclusion Criteria
- •1. Patient is willing and able to provide written informed consent for the
- •study prior to the performance of any study-specific procedures.
- •2. Patient is >= 18 years of age.
- •3. 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.
- •4. Patient must have measurable disease per Response Evaluation Criteria in
- •Solid Tumors, Version 1.1 (RECIST v1.1).
- •5. Patient has Eastern Cooperative Oncology Group (ECOG) performance status
- •(PS) of 0 to 1 (Appendix B).
- •Disease and FGFR2 status
- •6. Overall, patient has documented FGFR2 alteration in blood and/or tumor per
- •local assessment as defined by:
- •a. FGFR2 fusion or other rearrangement as detected by DNA or RNA sequencing or
- •break-apart fluorescence in situ hybridization (FISH).
- •b. FGFR2 amplifications must either include an amplified FGFR2 locus with copy
- •number >= 8 (FGFR2 probe: reference ratio >= 4 per FISH) in tumor tissue or be
- •defined as FGFR2 amplified by validated next-generation sequencing (NGS) test
- •(including but not limited to FoundationOne CDx, Tempus xT, Caris MI, or
- •Guardant360). No amplification cutoff is defined for circulating tumor DNA
- •c. FGFR2 mutations must include one or more of the following primary oncogenic
- •FGFR2 mutations or acquired FGFR2 resistance mutations:
- •o H167_N173del, S252X, P253X, F276C, Y375X, C382X, M537X, N549X, V564X,
- •E565X, L617X, K641X, K659X, and R664X (numbering based on mesenchymal isoform
- •IIIc; X represents any amino acid change except a synonymous mutation). Other
- •potentially oncogenic and/or resistance FGFR2 mutations may be considered but
- •must be approved by the Sponsor prior to enrollment.
- •d. Other potential FGFR2-dependent tumor types may be considered for Part 1.
- •7. Patient has a histologically or cytologically confirmed diagnosis of
- •unresectable or metastatic CCA or other unresectable or metastatic solid tumor.
- •8. Patient has documented FGFR2 genomic alteration (fusion, amplification, or
- •mutation) in blood and/or tumor tissue per local assessment. Patients with
- •other potential oncogenic FGFR2 alterations (eg, FGFR2 protein or mRNA
- •overexpression) and other tumor types known to exhibit an FGFR2 oncogenic
- •alteration may be eligible for the dose escalation (Part 1) of the study after
- •consultation with the Sponsor.
- •9. Patient agrees to provide archived tumor tissue (if available) or is willing
- •to undergo pretreatment tumor biopsy (if considered safe and medically
- •feasible) to assess FGFR2 status. If the patient does not have available
- •archived tumor tissue or tumor amenable to tumor biopsy, he/she may be eligible
- •for the study upon consultation with the Sponsor.
- •10. Patient will enroll based on their tumor type and prior therapy status:
- •Cholangiocarcinoma:
- •a. Groups 1A: patient must have a confirmed diagnosis of unresectable or
- •metastatic CCA with FGFR2 fusion or other rearrangement (per local assessment
- •of blood and/or tumor) and has been previously treated with chemotherapy and
- •has received prior treatment with an FGFRi.
- •b. Groups 2A: patient must have a confirmed diagnosis of unresectable or
排除标准
- •Patients who meet one or more of the following criteria will not be considered
- •eligible to participate in the clinical study:
- •1. Patient has a cancer other than FGFR2 fusion/rearrangement positive CCA and
- •has a known primary driver alteration that is amenable to approved targeted
- •therapy (eg, EGFR, ALK, ROS1, RET, HER2, BRAF, IDH1, KRAS). Patients may be
- •eligible after consultation with the Sponsor.
- •2. Patient has ongoing clinically significant FGFRi-induced retinal detachment
- •or an ongoing clinically significant corneal or retinal disorder.
- •3. Patient does not have the following adequate organ function assessments
- •within 7 days prior to the first dose of RLY-4008:
- •a. Platelet count >=75 × 109/L (platelet transfusion may be used to reach 75 ×
- •109/L but must have been administered at least 2 weeks prior to the first dose
- •of RLY-4008)
- •b. Absolute neutrophil count (ANC) >= 1 × 109/L
- •c. 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)
- •d. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 3 × the
- •upper limit of normal (ULN) if no hepatic metastases are present; < 5 × ULN if
- •metastases are present
- •e. Total bilirubin < 1.5 × ULN; < 3 × ULN with direct bilirubin < 1.5 × ULN in
- •the presence of Gilbert*s disease
- •f. Estimated (including Cockcroft-Gault, Modification of Diet in Renal Disease
- •[MDRD], or Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]
- •formulas) or measured creatinine clearance > 50 mL/min (Appendix A)
- •g. Serum phosphate < 7.0 mg/dL (2.3 mmol/L)
- •4. Patient has active infection, including human immunodeficiency virus (HIV),
- •hepatitis B virus (HBV) and/or hepatitis C virus (HCV).
- •a. Active HIV is defined by positivity for HIV 1 or HIV 2 antibodies.
- •HIV-positive patients are allowed if all of the following criteria are met:
- •CD4+ count >= 350/µL, undetectable viral load, receiving antiretroviral therapy
- •(ART) that does not interact with study drug (patients should be on established
- •ART for at least 4 weeks), and no HIV/AIDS-associated opportunistic infection
- •in the last 12 months.
- •b. Active HBV is defined by a positive HBV surface antigen (HBsAg) result.
- •Patients with a past or resolved HBV infection (defined as the presence of
- •hepatitis B core antibody [anti-HBc], absence of HBsAg, and serum HBV DNA <
- •1000 IU/mL) are eligible. Patients with well-controlled HBV, indicated by the
- •presence of HBsAg with serum HBV DNA <500 IU/mL are also eligible.
- •c. Patients positive for HCV antibody are eligible only if polymerase chain
- •reaction (PCR) is negative for HCV RNA.
- •5. Patient has a QT interval corrected using Fridericia*s formula (QTcF) > 480
- •msec. Patient has a history of prolonged QT syndrome or torsades de pointes.
- •Patient has a familial history of prolonged QT syndrome.
- •6. Patient has clinically significant, uncontrolled cardiovascular disease
- •including congestive heart failure Grade 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
- 另有 2 项未显示
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