Advanced solid tumors or Lymphoma
Conditions
Interventions
HG146 5mg group:HG146 5mg
HG146 10mg group:HG146 10mg
HG146 15mg group:HG146 15mg
HG146 20mg group:HG146 20mg
HG146 combination with PD-(L)1 inhibitor group:HG146 combination with PD-(L)1 inhibitor
Sponsors
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Aged >=18 years, gender is not limited; 2. Indications for Phase Ia and Phase Ib dose escalation: advanced/metastatic malignant solid tumors or lymphomas diagnosed by histology or cytology that have progressed after standard therapy or currently have no standard therapy available; 3. Indications for Phase Ib Combination Expansion Phase: Cohort 1, advanced malignant solid tumors or lymphomas confirmed by pathology or cytology, no standard treatment, or failure of standard treatment, or inaccessibility of standard treatment, or refusal to accept standard treatment, Patients who have not received anti-PD-(L)1 antibody therapy (including but not limited to MSI-H/dMMR advanced solid tumors, TPS>=1% non-small cell lung cancer without driver gene, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, gastric cancer , liver cancer, renal cell carcinoma, urothelial cell carcinoma, etc.); cohort 2, pathologically or cytologically confirmed advanced malignant solid tumor or lymphoma, no standard therapy, or standard therapy failure, or intolerance to standard therapy, or Those who refuse to accept standard treatment and whose disease progresses after treatment with anti-PD-(L)1 antibody; 4. According to RECISTv1.1 criteria, there is at least 1 measurable target lesion, and the lesion has not received radiation therapy (for solid tumors); or according to Lugano2014 criteria, there is at least 1 measurable or evaluable lesion ( for lymphoma); 5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; 6. Expected survival >= 12 weeks; 7. The function of each organ is good, the specific indicators are as follows: No blood transfusion or colony-stimulating factor treatment within 2 weeks before screening: absolute neutrophil count (ANC) >=1.5 x 10^9/L ( >=1,500/µL) Platelet count >= 100 x 10^9/L (>=100,000/µL) and hemoglobin > 9.0g/dL ( > 5.6mmol/L); Activated partial thromboplastin time (APTT) and international normalized ratio (INR)= 50ml/min (according to the Cockcroft-Gault formula); 8. Cardiac function: Hemodynamically stable and left ventricular ejection fraction (LVEF) >= 50% as determined by echocardiography (ECHO) or radionuclide active angiography (MUGA); or New York Heart Association (NYHA) ) Heart failure classification; 9. Eligible patients (male and female) of childbearing potential must agree to use a reliable contraceptive method (barrier method or abstinence) with their partner during the trial and for at least 3 months after the last dose; female patients of childbearing age before enrollment A blood or urine pregnancy test within 7 days must be negative. Infertile female patients must meet at least one of the following criteria, and all other female patients (including those with tubal ligation) are considered fertile: Postmenopausal status, defined as follows: In the absence of other causes at least Menopause for 12 consecutive months; Hysterectomy and/or bilateral oophorectomy; Medically proven ovarian failure; 10. Patients must be informed and consented to this
Exclusion criteria
Exclusion criteria: 1. Those who are known to be allergic to any active ingredient or excipient of the study drug; 2. Currently or in the past with other malignant tumors (except for adequately treated skin basal cell carcinoma or squamous cell carcinoma, cervical carcinoma in situ), unless radical treatment has been performed and there is no evidence of recurrence and metastasis within the past 5 years; 3. Received any anti-tumor therapy, including chemotherapy, growth factors, and small molecule targeted therapy within 28 days before the first dose of the study treatment or within 5 half-lives of the drug (whichever is shorter); the first dose of the study treatment Immunotherapy or monoclonal antibody therapy for the first 1.5 months; 4. Received immunosuppressive therapy with systemic corticosteroids within 14 days before the first dose of study treatment; 5. Received major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks before the first administration, or required elective surgery during the trial; 6. The presence of clinically significant active infections: bacterial, fungal or viral infections, including tuberculosis, hepatitis B virus (HBV), hepatitis C virus (HCV), COVID-19, syphilis, human immunodeficiency virus (HIV) Infection or known acquired immunodeficiency syndrome (AIDS)-related disease; 7. Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past (limited to Phase Ib combination therapy stage); 8. Autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, etc.) and other diseases that damage the immune system as judged by the investigator (limited to the phase Ib combination drug stage) ; 9. History of adrenal insufficiency (including patients using replacement therapy) (limited to phase Ib combination therapy); 10. Patients with symptomatic brain metastases requiring steroid therapy. Patients with previously diagnosed brain metastases, who have completed treatment prior to screening and have recovered from acute adverse reactions due to radiotherapy or surgery, have discontinued corticosteroid therapy for brain metastases for at least 4 weeks, and are currently neurologically stable, are eligible to participate this research; 11. Unstable or severe concurrent diseases, such as pancreatitis, severe/unstable angina, QT interval (QTcF) prolongation corrected by Fridericia formula >450 ms (calculated as three repetitions) within 6 months before enrollment Mean of readings at intervals of no more than 2 min and no history of torsades de pointes or symptomatic QTc abnormalities), symptomatic congestive heart failure, myocardial infarction and/or pulmonary hypertension, life-threatening patients receiving maintenance therapy of ventricular arrhythmias, strokes and uncontrolled severe seizures; 12. Suffering from severe lung disease (history of or combined with severe interstitial lung disease, severe chronic obstructive pulmonary disease, severe pulmonary insufficiency, and symptomatic bronchospasm); 13. Current or recent (within 3 months) suffering from any gastrointestinal disease that may affect the ability to swallow and/or absorb the study drug (eg, gastrointestinal surgery, malabsorption syndrome, etc.); 14. Pregnant or lactating women; 15. Patients who use drugs or alcohol for a long time, which affects the evaluation of the test results; 16. Other conditions deemed inappropriate by the
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Area under the curve (AUC);Plasma drug peak concentration (Cmax);Time to peak (Tmax);Half life (T1/2);objective response rate (ORR);Progress-free survival (PFS);Duration of overall response (DOR);Best overall response (BOR); | — |
Primary
| Measure | Time frame |
|---|---|
| Adverse Event;Severe Adverse Event (SAE);Dose limiting toxicity (DLT);Phase 2 recommended dose (RP2D); | — |
Countries
China
Contacts
Public ContactWang Yongsheng
West China Hospital of Sichuan University
Outcome results
None listed