Advanced/Metastatic Solid tumors and Lymphomas
Conditions
Interventions
Experimental group:DNV3
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Full understood the study procedure and content, signed the informed consent voluntarily; 2.Aged >=18 when signed inform consent(For part I, aged 16 to 65 years old), male or female; 3.Histopathological diagnosis confirmed subject with advanced/metastatic solid tumors and Lymphomas patients, who are unresectable and failed after standard treatment, or cannot tolerate standard treatment and /or have no standard treatment; 4.Willing to provide archived tumor tissue sections or fresh tissue sections (optional); 5.ECOG score was 0 or 1; 6.Expected survival >= 3 months; 7.At least 1 measurable outside CNS lesion (solid tumor based on RECIST v1.1 criteria; lymphomas based on Lugano 2014 criteria); 8.Those who have received any chemotherapy drugs at least 3 weeks before the first application(such as nitrosourea and mitomycin C,should be more than 6 weeks before the last chemotherapy);Those received monoclonal antibody (including antibody/drug against immune checkpoints, such as PD-1,PD-L1,CTLA-4) at least 4 weeks ago; or other small molecular targeted drug at least 2 weeks ago(or 5 half-life, chosing the longer one); 9.Radiotherapy (>= 30% bone marrow exposure) have be finished for at least 4 weeks before the first application existence of Grade 1 or less toxicity due to previous radiotherapy; 10.Those who have undergone general anesthesia major surgey at least 4 weeks ago before the first application;local/epidural anesthesia surgeyundergone at least 2 weeks ago; 11.Those have received antitumor biotherapy (vaccine,cytocine or growth factor that can control tumor) have been completed for at least 4 weeks; 12.Adequate organ function:Blood system (in the absence of blood transfusion or hematopoietic stimulating factor winthin 14 days); ANC >= 1.0x10^9/L; PLT >= 90x10^9/L; Hb>=90g/L; TBIL =2.8g/dLCR=50mL/min (when C>1.5xULN, use Cockcroft-Gault Formula to calculate CCR); aPPT = 50 can be considered postmenopausa if she has had amenorrhea for 12 months or more after discontinuation of exogenous hormone therapy, adiation-induced oophorectomy and last menstruation occurring in 1 year agoor chemotherapy-induced menopause and the last menstrual period till now is more than 1 year, women who have undergone surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); 15.All reproductive age subjects(female and male)should use contraceptives(such as hormone,barrier
Exclusion criteria
Exclusion criteria: 1.Have previously received antibody / drug treatment against LAG-3 immune checkpoints; 2.Have previously received CAR-T; 3.Patients who participated in other interventional clinical trials within 4 weeks before the first application; 4.Have received live or attenuated vaccine within 4 weeks before administration; 5.Patients with other malignant tumors within the past 5 years, except for those who have cured skin basal cell carcinoma and superficial bladder cancer, except for breast and cervical carcinoma in situ; 6.Patient with symptomatic or active progression of central nervous system (CNS) can be enrolled if they had a treated CNS lesion or untreated asymptomatic subjects and fit the following criterias: past history of intracranial hemorrhage or spinal cord hemorrhage;Subjects did not receive stereotactic radiotherapy or whole-brain radiotherapy within 4 weeks before administration;subjects without persistent-usage of corticosteroids during CNS treatment were allowed to receive a steady dose of anticonvulsants; metastases are located at the cerebellum or supratentorial area (i.e. no metastases to the midbrain, pons, medulla, or spinal cord); Imaging examination at least 4 weeks prior to administration showed no progress and any neurological symptoms had returned to baseline; 7.Have any types of active autoimmune diseases or have a history of autoimmune disease with expectations to relapse or clinical symptom, patients need systematic steroid or immune inhibitary therapy.Children with vitiligo or cured asthma/specific responses may be enrolled. People with intermittent bronchodilators or topical steroid injections, type I diabetes, and stable hypothyroidism who require hormone replacement therapy should not be excluded; 8.There are complication that require treatment with immune inhibitory drugs, or that require immune inhibitory doses (prednisone > 10mg/day or equivalent dose of similar drugs) for systematic treatment; In the absence of active autoimmune disease, patient can inhale or local administration topical corticosteroids, or adrenal hormone equivalent 480ms according to the Fridericia Formula correction, have cerebrovascular disease (CVA within 6 months before the first application or history of TIA), uncontrolled diabetes, uncontrolled hypertension(systolic blood pressure>= 150mmHg and/or diastolic blood pressure>= 100mmHg after treatment), active gastrointestinal ulcer, active bleeding, etc; 10.There is uncontrollable effusion in the chest, pericardium after proper Intervene or peritoneal cavity need frequent draining (previous drainage 2 times or more); 11.Patients current or previous with interstitial lung disease, allergic pneumonia, pulmonary fibrosis, acute lung disease, etc; 12.Have active infection that need system treatment; 13.Have active tuberculosis infection; Have a history of tuberculosis ; 14.HBsAg positive and HBV-DNA higher than the upper limit of normal value; HCV-Ab posi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability;Total lifetime; | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics;Pharmacodynamics;Immunogenicity;Objective remission rate;Duration of remission;Disease Control Rate;Progression-free survival; | — |
Countries
China
Contacts
Public ContactShi Yuankai
Outcome results
None listed