Advanced Solid Tumors
Conditions
Interventions
Single drug group:Intravenous infusion of BEBT-908 drug
Combination group:Intravenous infusion of BEBT-908 drug and intramuscular injection of fulvestrant injection
Combination group:Intravenous drip of BEBT-908 drug and PD-1 monoclonal antibody
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged >= 18-<=75 years, male or female; 2. The subject after a comprehensive understanding, willing to sign the informed consent form (ICF); 3. Patients with histologically or cytologically confirmed advanced solid tumors, including: BEBT-908 monotherapy group: advanced malignant solid tumor patients with standard treatment failure or lack of effective treatment (regardless of tumor type); BEBT-908 plus flurvistrant group: hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) locally advanced or metastatic postmenopausal female and male breast cancer patients who failed standard treatment;Definition of standard treatment failure:(1)evidence of recurrence of disease progression and not receiving treatment of metastatic disease during or 12 months after (new) adjuvant endocrine therapy;(2)evidence of recurrence of disease progression 12 months after completion of (new) adjuvant endocrine therapy,and then evidence of disease progression during or after first-line endocrine therapy for metastatic diseases;(3)newly diagnosed advanced breast cancer has evidence of disease progression only during or after first-line endocrine therapy; (4) treatment with aromatase inhibitors (i.e.,recurrence or disease progression occurs during or after the treatment of letrozole,anastrozole,Exemetan,etc.),aromatase inhibitor therapy may not be the last treatment. Patients need to meet any of the first three conditions and the fourth condition; BEBT-908 combined with PD-1 monoclonal antibody treatment group, each tumor should meet at least the following conditions:(1) NSCLC: metastatic non-small cell lung cancer patients with metastatic non-small cell lung cancer during or after platinum chemotherapy.Patients with tumors with EGFR or ALK gene mutations should have received targeted therapy for these mutations and disease progression;(2)SCLC:patients with metastatic small cell lung cancer (SCLC)with metastatic small cell lung cancer who developed during or after platinum-based chemotherapy and at least one other therapy.(3)HNSCC:Patients with recurrent or metastatic squamous cell carcinoma of the head and neck during or after platinum-containing chemotherapy;(4)urothelial carcinoma: patients with locally advanced or metastatic urothelial cancer progressed during or after platinum-containing chemotherapy, or within 12 months after receiving neoadjuvant or adjuvant therapy with platinum-containing chemotherapy;(5) Colorectal cancer:metastatic colorectal cancer patients treated with fluorouracil, oxaliplatin and irinotecan alone or in combination with ipilimumab;(6)Esophageal cancer:recurrent locally advanced or metastatic esophageal squamous cell carcinoma patients with disease progression after first-line or more systematic treatment; (7) Cervical cancer: recurrent or metastatic cervical cancer patients with disease progression during or after chemotherapy;(8) Hepatocellular carcinoma patients with (HCC): progression during or after first-line treatment;(9) Renal cell carcinoma:patients with advanced renal cell carcinoma who have received antiangiogenic therapy. 4. There is at least one measurable focus defined by RECIST V1.1; tumor lesions that have previously received radiotherapy or other local treatment are considered measurable lesions only if the disease progression at the treatment site is clearly recorded after the completion of the treatment. 5. The ECOG score is 0-1, and there has been no decline in physi
Exclusion criteria
Exclusion criteria: 1.Symptomatic,advanced patients (patients with visceral crisis) who have disseminated to the viscera and are at risk of life-threatening complications in the short term, and patients with inflammatory breast cancer cannot be included in the BEBT-908 combined with fulvestrant group; 2.Patients with malignant tumors accompanied by gastrointestinal invasion, active gastrointestinal ulcer, intestinal obstruction, active gastrointestinal bleeding, perforation can not be included in the BEBT-908 combined with PD-1 monoclonal antibody treatment group; 3.Known or symptomatic active CNS metastasis, manifested as the presence of clinical symptoms, cerebral edema, spinal cord compression, carcinomatous meningitis, leptomeningeal disease, and/or progressive growth; 4.Received any other antineoplastic therapy (including cytotoxic chemotherapy, molecular targeted therapy, immunotherapy or other biological therapy) within 4 weeks before the first use of the research drug, mitomycin or nitrosamine within 6 weeks, small molecule targeted drugs at least 2 weeks or at least 5 half-lives between the last administration (whichever is the longer), and traditional Chinese medicine with antineoplastic indications at least 2 weeks from the last administration; 5.Received blood transfusion, recombinant human thrombopoietin, recombinant human interleukin-11, erythropoietin and granulocyte colony stimulating factor within 2 weeks before the first use of the research drug; 6.Those who had undergone major surgery requiring general anesthesia or did not withdraw from other clinical trials within 4 weeks before entering the study; within 2 weeks before entering the group, had undergone surgery requiring local / epidural anesthesia and the patient had not yet recovered (except tissue biopsy); 7.Patients who have received PI3K inhibitors or HDAC inhibitors combined with PD-1 monoclonal antibody cannot be enrolled in the treatment group combined with PD-1 monoclonal antibody, and patients who have received PI3K inhibitors or HDAC inhibitors combined with flurvist cannot be enrolled in the combination treatment group; 8.Known to have a history of allergy or suspected allergic symptoms to any component of BEBT-908, flurvist group, or PD-1 monoclonal antibody. 9.Patients received the following treatments in the 7 days before entering the study: drugs that are known to be strong inhibitors or inducers of CYP 3A4; drugs that are known to significantly prolong QT intervals or torsion ventricular tachycardia (antiarrhythmic drugs such as quinidine, isopropylamide, procainamide, sotalol, etc.); 10.Immune-related adverse events with grade 3 or more in immunotherapy could not be included in the combined PD-1 monoclonal antibody group. 11.Patients with active, previous and possibly recurrent autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.) cannot be enrolled in the BEBT-908 plus PD-1 monoclonal antibody group. the following patients are allowed: type I diabetes, autoimmune thyroiditis with alternative treatment; 12.Patients who have received systemic corticosteroids (prednisone > 10mg/ days or equivalent doses) or other immunosuppressants within 14 days before the first administration; except for the following: treatment with local, ocular, intra-articular, intranasal and inhaled corticosteroids, and short-term use of corticosteroids for prophylaxis, such as contrast media; 13.Current or previous history of interstitia
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| ORR;Pharmacokinetics;Safety and tolerance;RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| DCR;TTR;DOR;PFS;OS; | — |
Countries
China
Contacts
Public ContactQian Changgeng
Outcome results
None listed