癌研連線CancerLink
已終止 NCT04000529

TNO155聯合Spartalizumab或Ribociclib用於選定惡性腫瘤的第一b期研究

非小細胞肺癌大腸直腸癌頭頸癌食道癌Phase IIII 期IV 期EGFRALKKRASPD-L1

本研究為第一b期、多中心、開放標籤研究，探討TNO155聯合spartalizumab或ribociclib，包含劑量遞增部分及隨後的劑量擴展部分，對象為患有晚期實體瘤的成年受試者。 此兩個治療組平行招募受試者，以描述其安全性、耐受性、藥物動力學（PK）、藥效學（PD）及初步抗腫瘤活性。 研究治療持續進行直至受試者出現不可接受的毒性、疾病惡化

適應症：Non-small Cell Lung Carcinoma、Head and Neck Squamous Cell Carcinoma、Esophageal SCC、Gastrointestinal Stromal Tumors、Colorectal Cancer

收案條件

納入條件

  • Signed informed consent must be obtained prior to participation in the study.
  • Age ≥ 18 years. For Japan only: written consent is necessary both from the patient and his/her legal representative if he/she is under the age of 20 years.
  • ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.
  • Dose escalation part: Patients with advanced solid tumors, with evaluable disease as determined by RECIST version 1.1, and fit into one of the following groups:
  • a. For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT NSCLC, after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.
  • ii. Advanced HNSCC or esophageal SCC, after progression on or intolerance to platinum-containing combination chemotherapy.
  • iii. Advanced CRC, after progression on or intolerance to all standard-of-care (SOC) therapy per local guidelines.
  • b. For TNO155 plus ribociclib combination: Advanced solid malignancies with the exception of CRC or GIST, after progression on or intolerance to all SOC therapy per local guidelines. The exclusion of CRC applies only as of Protocol Amendment 4.
  • Dose expansion part: Patients with advanced solid tumors, with at least one measurable lesion as determined by RECIST version 1.1, who fit into one of the following groups:
  • a. For TNO155 plus spartalizumab combination: i. Advanced EGFR WT, ALK WT, KRAS G12C NSCLC after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.
  • ii. Advanced EGFR WT, ALK WT, KRAS WT NSCLC, after progression on or intolerance to platinum-containing combination chemotherapy and after progression on anti-PD-1 or anti-PD-L1 therapy.
  • iii. Advanced HNSCC, after progression on or intolerance to, platinum-containing combination chemotherapy.
  • b. For TNO155 plus ribociclib combination: i. Advanced EGFR WT, ALK WT, KRAS WT NSCLC, after progression on or intolerance to platinum-containing chemotherapy and anti-PD-1 or anti-PD-L1 therapy ii. Advanced HNSCC, after progression on or intolerance to all SOC per local guidelines
  • Patients with NSCLC whose tumors harbor genomic aberrations for which SOC targeted therapies exist and are locally approved and available must have had progression on or after, or intolerance to, the SOC targeted therapy/therapies as indicated
  • Patients must have a site of disease amenable to biopsy

排除條件

  • Prior treatment with a MAPK pathway inhibitor
  • Clinically significant cardiac disease or risk factors
  • Use of any agent known to prolong the QT interval unless it can be permanently discontinued for the duration of study (see list in Section 6.2.2).
  • History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease) or impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drugs
  • Symptomatic CNS metastases which are neurologically unstable
  • Insufficient bone marrow function at screening:
  • Absolute Neutrophil Count (ANC) \< 1.5 x 109/L.
  • Hemoglobin \< 9.0 g/dL.
  • Platelets \< 75 x 109/L for TNO155 plus spartalizumab combination; \< 100 x 109/L for TNO155 plus ribociclib combination.
  • Insufficient hepatic or renal function at screening:
  • Serum total bilirubin \> upper limit of normal (ULN) or, for TNO155 plus spartalizumab combination only, if liver metastases are present at baseline, serum total bilirubin \> 1.5 x ULN. An exception for either combination is for patients with Gilbert's syndrome, who are excluded if total bilirubin \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 x ULN for TNO155 plus spartalizumab combination or \> 2.5 x ULN for TNO155 plus ribociclib combination, or \> 5 x ULN for either combination if liver metastases are present.
  • Creatinine clearance \< 60 mL/min (calculated using Cockcroft-Gault equation).
  • Pregnant or breast-feeding (lactating) women.
  • History of severe hypersensitivity reactions to other mAbs.
  • Active, known or suspected autoimmune disease.
  • History of or current interstitial lung disease or pneumonitis grade ≥ 2.
  • Human Immunodeficiency Virus (HIV) infection, unless the patient is on antiviral therapy and has undetectable viral load.
  • Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
  • Systemic chronic steroid therapy
  • Patients who discontinued prior anti-PD-1 therapy due to an anti-PD-1-related toxicity.
  • Systolic Blood Pressure (SBP) \< 90 mmHg.
  • International Normalized Ratio (INR) \> 1.5 (unless the patient is receiving anticoagulants and the INR is within the therapeutic range of intended use for that anticoagulant within seven days prior to the first dose of study drug).
  • History of HIV infection (testing not mandatory)
  • Currently receiving any of the following substances and cannot be discontinued seven days prior to Cycle 1 Day 1:
  • Concomitant medications or herbal supplements, that are strong inducers or inhibitors of CYP3A4/5,
  • Medications that have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
  • Previous treatment with a CDK4/6 inhibitor.
  • Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment.

收案條件維持 ClinicalTrials.gov 原始英文登錄資料，實際收案資格以研究團隊的正式評估與受試者同意書為準。資料來源：ClinicalTrials.gov，每兩週自動更新，最後同步：2026年10月8日。