癌研連線CancerLink
已终止 NCT04000529

TNO155联合Spartalizumab或Ribociclib用于选定恶性肿瘤的第一b期研究

非小细胞肺癌结直肠癌头颈癌食管癌Phase IIII 期IV 期EGFRALKKRASPD-L1

本研究为第一b期、多中心、开放标签研究，探讨TNO155联合spartalizumab或ribociclib，包含剂量递增部分及随后的剂量扩展部分，对象为患有晚期实体瘤的成年受试者。 此两个治疗组平行招募受试者，以描述其安全性、耐受性、药物动力学（PK）、药效学（PD）及初步抗肿瘤活性。 研究治疗持续进行直至受试者出现不可接受的毒性、疾病进展

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

入组条件

纳入标准

  • 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

排除标准

  • 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.

入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。