Recurrent or metastatic advanced malignant tumors
Conditions
Interventions
Phase Ia: Dose escalation stage:Gh2616 tablets for oral therapy
Phase Ib: Dose Expansion Study:Gh2616 tablets for oral therapy
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female aged 18 years or older. 2. The researchers assessed the following two points and considered it suitable to participate in this study: a. The subjects fully understood the requirements of this study and voluntarily signed a written informed consent; b. Be able to comply with the medication requirements of the study and all procedures and evaluations related to the study. 3. Tumor types that meet the following criteria: Stage Ia: Subjects with recurrent or metastatic advanced malignant tumors diagnosed histologically or cytologically with standard treatment failure or intolerance or no standard treatment, including but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), triple negative breast cancer (TNBC), Urothelial carcinoma (BLCA), colorectal cancer (CRC), etc. Stage Ib: Subjects with histologically or cytologically confirmed, laboratory-confirmed recurrent or metastatic advanced malignant tumors with TP53 gene mutation and genomic doubling (WGD) features, including but not limited to high-grade serous ovarian cancer (HGSOC), uterine carcinosarcoma (UCS), non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), Triple negative breast cancer (TNBC), urothelial carcinoma (BLCA), colorectal cancer (CRC), etc. The specific requirements for each tumor type are as follows: 1) High-grade serous ovarian cancer: platinum-resistant ovarian cancer that has progressed/recurred after at least first-line and more platinum-containing chemotherapy, or platinum-sensitive ovarian cancer that has progressed/recurred after at least second-line and more platinum-containing chemotherapy. "Platinum-resistant" was defined as =6 months between the time of discovery of tumor recurrence and the time of the last prior chemotherapy. The interval should be calculated from the date of the last platinum drug treatment to the date of disease progression. 2) Uterine carcinosarcoma: Progression/recurrence after at least first-line and more platinum-containing chemotherapy. 3) Non-small cell lung cancer: progression or recurrence after treatment with at least a platinum-containing regimen, and known positive gene drivers such as epidermal growth factor receptor (EGFR) sensitive mutation/anergic lymphoma kinase (ALK) fusion /c-ros oncogene-1 (ROS1) fusion gene require progression or recurrence after standard targeted therapy. 4) Small cell lung cancer: Progression or recurrence after treatment with at least a platinum-containing regimen. 5) Triple-negative breast cancer: progression/recurrence after at least first-line chemotherapy. 6) Urothelial carcinoma: Progression/recurrence after at least first-line and above standard treatment. 7) Colorectal cancer: progression/recurrence after at least second-line and above standard treatment. Note: Participants with adjuvant therapy who developed disease progression less than 6 months after the end of treatment could be considered to have received first-line treatment; 4. Expected survival >=12 weeks. 5. ECOG Physical status Score (Appendix 1: ECOG Physical Status Scale) 0 or 1; 6. Have at least one measurable lesion according to RECIST 1.1 (Appendix 2
Exclusion criteria
Exclusion criteria: 1. GH2616 tablets were treated with chemotherapy within 21 days before the first administration, or with anti-tumor agents such as radiotherapy, biotherapy, endocrine therapy, targeted therapy, and immunotherapy within 28 days before the first administration. In addition, special provisions are made for the following anti-tumor drugs or therapies: 1) nitrosourea or mitomycin C is treated within 6 weeks before the first administration of the investigational drug; 2) Oral fluorouracil, small molecule targeted drugs and Chinese medicines with anti-tumor indications within 14 days before the first use of the study drug; 3) Local palliative radiotherapy was prescribed within 14 days prior to the first use of the study drug. 2. Received other investigational drugs or treatments that are not on the market within 28 days prior to initial dosing. 3. In the 28 days prior to the first administration of GH2616 tablets, acute toxicity due to previous antitumor therapy did not return to the baseline level specified by the National Cancer Institute General Terminology Standard for Adverse Events (NCI CTCAE) version 5.0 470 ms (increased ECG frequency if clinically indicated). A variety of clinically significant cardiac rhythm, conduction, and resting ECG morphological abnormalities, such as complete left bundle branch block, degree III block, degree II block, and PR interval > 250 ms. Various factors that may increase the risk of prolonged QTc or arrhythmia events, such as heart failure, hypokalemia, congenital long QT syndrome, immediate family history of long QT syndrome or sudden unexplained death before the age of 40, are taking any medications with known prolonged QT interval. 5. There is persistent or active infection, including: a) Active hepatitis B (hepatitis B surface antigen (HbsAg) positive with hepatitis B virus deRNA (HBV-DNA) > 500 IU/ml or 1000 cps/ml or lower limit of study center detection [only when lower limit of study center detection is higher than 500 IU/ml or 1000 cps/ml]), Allow antiviral therapy other than interferon; Active hepatitis C (subjects who are positive for hepatitis C virus (HCV) antibodies but have hepatitis C virus ribonucleic acid (HCV-RNA) < the lower limit of the study center detection are allowed to be included); b) HIV infected persons (HIV 1/2 antibody positive); c) Known active syphilis infection. 6. Central nervous system (CNS) metastases with symptomatic or active progression. Asymptomatic subjects with CNS lesions, treated or untreated, are eligible only if they meet all of the following criteria: a) The presence of measurable lesions outside the CNS as determined by RECIST 1.1. b) Subjects had no history of intracranial or spinal bleeding. c) Subjects did not undergo stereotactic radiation therapy whole brain radiation therapy and did not undergo neurosurgical resection within 28 days prior to initiation of study therapy. d) The subject did not use corticosteroids continuously during treatment for CNS disease. e) Metastasis is limited to the cerebellum or supratentorial area (i.e., no metastasis to the midbrain, pons, medulla, or spinal cord). f) There is no evidence of intermediate progress between completion of CNS targeted therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety, tolerability, and dose limiting toxicity (DLTs) of GH2616 tablets in advanced solid tumors; | — |
Secondary
| Measure | Time frame |
|---|---|
| Evaluation indicators for anti-tumor activity; | — |
Countries
China
Contacts
Public ContactZhengbo Song
Zhejiang Cancer Hospital
Outcome results
None listed