Advanced recurrent or metastatic solid tumors
Conditions
Interventions
Experimental group:Oral Lucitanib+Intravenous Toripalimab(240mg/dose)
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Phase Ib: 1. Able to understand and voluntarily sign a written informed consent form (ICF); 2. Male or female aged 18-75 years (inclusive); 3. Patients with advanced recurrent or metastatic solid tumors diagnosed by histopathology,who have failed standard treatment (disease progression after treatment or intolerable toxicity and side effects of treatment) or have no effective treatment, and who are unwilling to receive standard treatment or are not suitable for standard treatment (Phase Ib) 4. Female subjects of childbearing age must undergo a pregnancy test within 7 days before starting the study drug, and the result must be negative. They must also be willing to take adequate contraceptive measures during the trial and within 6 months after the last administration of the investigational drug. Male subjects whose partners are women of childbearing age must take adequate contraceptive measures during the trial and within 6 months after the last administration of the study drug. Female subjects who have undergone sterilization surgery or have reached menopause are excluded. 5. ECOG physical condition score = 1 point; 6. Have adequate bone marrow, liver and kidney function: 7. Urine protein <1+; if urine protein = 1+, the 24-hour proteinuria should be <1.0 g/24h; 8. International normalized ratio (INR) =1.5; activated partial prothrombin time (APTT) =1.5×ULN; 9. Body weight =40 kg; 10. According to the judgment of the investigator, the patient's life expectancy is =12 cycles Inclusion criteria: Phase II: 1. Able to understand and voluntarily sign a written informed consent form (ICF); 2. Male or female aged 18-75 years (inclusive); 3. Advanced solid tumors confirmed by histopathology (hepatocellular carcinoma can be confirmed by clinical evidence), the study cohorts are as follows: Nasopharyngeal carcinoma immune failure Nasopharyngeal carcinoma chemotherapy failure Gastric adenocarcinoma (including esophageal gastric junction adenocarcinoma) Hepatocellular carcinoma (Child-Pugh =7 points), excluding fibrolamellar hepatocellular carcinoma; Small cell lung cancer Other solid tumors, etc. 4. According to the solid tumor response evaluation criteria (RECIST1.1), gastric adenocarcinoma: at least one measurable lesion outside the stomach; hepatocellular carcinoma, nasopharyngeal carcinoma, small cell lung cancer and other solid tumors: at least one measurable lesion; 5. Female subjects of childbearing age must undergo a pregnancy test within 7 days before starting the study drug, and the result must be negative. They must also be willing to take adequate contraceptive measures during the trial and within 6 months after the last administration of the investigational drug. Male subjects whose partners are women of childbearing age must take adequate contraceptive measures during the trial and within 6 months after the last administration of the study drug. Female subjects who have undergone sterilization surgery or have reached menopause are excluded. 6. ECOG physical condition score = 1 point; 7. Have adequate bone marrow, liver and kidney function: 8. Urine protein <1+; if urine protein = 1+, the 24-hour proteinuria should be <1.0 g/24h; 9. International normalized ratio (INR) =1.5; activated partial prothrombin time (APTT) =1.5×ULN; 10. Body weight =40 kg; 11. According to the judgment of the investigator, the patient's life expectancy is =12 cycles Inclusion criteria: The above inclusion criteria are II and all its cohorts share the f
Exclusion criteria
Exclusion criteria: Phase Ib and II: 1. Patients with active autoimmune diseases or a history of autoimmune diseases, including, but not limited to: hepatitis, interstitial pneumonia, uveitis, inflammatory bowel disease, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism (can be included after effective hormone replacement therapy); patients with vitiligo or asthma that has completely resolved in childhood, who do not need any intervention as an adult and require bronchodilators for medical intervention can be included; 2. Subjects who require systemic treatment with corticosteroids (>10mg/day prednisone effective dose) or other immunosuppressants within 14 days before the administration of the investigational drug. Inhaled or topical steroids and adrenal hormone replacement with a dose of >10mg/day prednisone effective dose are allowed in the absence of active autoimmune diseases; 3. Known allergy to antibody drugs, or allergy to the investigational drug and/or its excipients. 4. Subjects who had coughing up blood or hemoptysis within 28 days before enrollment (defined as coughing up =1 teaspoon of fresh blood or small blood clots or only coughing up blood without sputum), but blood in sputum is not excluded; 5. Imaging within 28 days before enrollment showed that the tumor surrounded important blood vessels or had the risk of invading blood vessels, and the investigator determined that entering the study would cause bleeding risk; 6. Toxicity related to previous anti-tumor treatment has not recovered to = CTCAE grade 1, excluding alopecia and neurotoxicity; 7. Suffering from other malignant tumors in the past 5 years (excluding basal cell carcinoma of the skin and cervical carcinoma in situ that have been effectively controlled); 8. Central nervous system (CNS) metastasis or malignant tumor-related epilepsy that requires clinical intervention. Patients with CNS metastases that have been treated and are stable for =3 months (no need for glucocorticoids or anti-epileptic drugs), as well as CNS metastases without brain metastasis-related symptoms, can participate in this study; 9. Patients who have received chemotherapy, molecular targeted therapy, immunotherapy, biological therapy, hormone therapy within 4 weeks before the first dose, or received anti-tumor Chinese medicine treatment within 2 weeks (subject to the indications in the Chinese medicine instructions, see Appendix 5 for details) and other systemic anti-tumor treatments; except for the following items: nitrosourea or mitomycin C within 6 weeks before the first use of the study drug; oral fluorouracil and small molecule targeted drugs within 2 weeks before the first use of the study drug or within 5 half-lives of the drug (whichever is longer); 10. Vaccinated with live vaccines within 4 weeks before the start of study treatment; 11. Received radical radiotherapy (including more than 25% bone marrow radiotherapy) within 4 weeks before the first dose, or received local palliative radiotherapy for bone metastases within 2 weeks; 12. Clinically uncontrollable serous effusion (such as pleural effusion that cannot be controlled by drainage or other methods); 13. Past or recent history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe lung function impairment, etc. 14. Cardiovascular system diseases 15. Arterial/venous thrombotic events or embolic events within 6 months before the first dose, such as ischemic cerebrovascu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase II-Objective Response rate;Phase Ib - Determine the recommended dose for phase II;Phase Ib-Safety;Phase Ib-Drug resistance; | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase II-Disease Control Rate;Phase II-Duration of Response;Phase II-Progression Free Survival;Phase II-Overall Survival;Phase II-Safety;Phase II-Drug resistance;PhaseII-Pharmacokinetic (PK) characteristics;PhaseIb-Pharmacokinetic (PK) characteristics;Phase Ib-Objective Response Rate;Phase Ib-Duration of Response;Phase Ib-Duration of Response;Phase Ib-Progression Free Survival;Phase Ib-Overall Survival; | — |
Countries
China
Contacts
Public Contactzhangli
Sun Yat-sen University Cancer Center
Outcome results
None listed