The Efficacy and Safety of the Bispecific Anti-PD-1/PD-L1 Antibody IBI318 Combined With Lenvatinib in NSCLC.

• Status: Recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is a prospective, single-arm phase II clinical study to evaluate the effectiveness of IBI318 combined with lenvatinib in subjects with advanced or metastatic non-small cell lung cancer who failed first-line PD-1/PD-L1 And safety research. After being screened to meet the inclusion criteria, they will receive IBI318 combined with lenvatinib until the disease progresses, death, toxicity is intolerable, informed consent is withdrawn, new anti-tumor therapy is started, or the treatment is terminated for other reasons specified in the plan.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hunan Province Tumor Hospital

Criteria

Inclusion Criteria:

• Eligible subjects selected for this study must meet all of the following criteria:

1. Sign written informed consent before implementing any trial-related procedures; 2. Age ≥18 years old and ≤75 years old; 3. Histological or cytological confirmation of locally advanced (IIIB-IIIC), metastatic or recurrent (stage IV) NSCLC (International Association for the Study of Lung Cancer and American Cancer Classification Joint Committee 8th Edition TNM Lung Cancer Staging), advanced or metastatic system Relapse after treatment failure and anti-PD-1/PD-L1 antibody treatment failure, as follows:

1) Only one anti-PD-1/PD-L1 antibody monotherapy or combination therapy is accepted in the advanced stage of the disease, and other immunotherapy is not allowed; 2) Previous anti-PD-1/L1 antibody monotherapy or combination therapy has the best curative effect (according to RECIST 1.1 criteria) as partial remission, complete remission, or stable disease for ≥6 months (defined as within 6 months from the first medication) No disease progression has occurred); 3) Disease progression confirmed by imaging studies occurred during or after the most recent treatment.

4. Histological specimens confirm that there is no sensitive mutation of EGFR gene, ALK, ROS1 gene fusion; 5. According to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1 version), there is at least one imaging measurable lesion. The lesions located in the radiation field of the previous radiotherapy can be regarded as measurable lesions if the progress is confirmed; 6. Subjects with brain metastases asymptomatic or with stable symptoms after local treatment are allowed to be included in the group, as long as the subjects meet the following conditions:

1) There are measurable lesions outside the central nervous system 2) no symptoms of the central nervous system or no worsening of symptoms within at least 2 weeks 3) No need for glucocorticoid therapy, or stop glucocorticoid therapy within 7 days before the first administration, or the dosage of glucocorticoid is stable and reduced to less than 10mg/day prednisone (or equivalent dose) within 7 days before the first administration ； 7. Subjects are allowed to receive palliative radiotherapy (including craniocerebral radiotherapy for symptomatic brain metastases), but the radiotherapy must be completed at least 1 week before enrollment, and the radiotherapy-related toxicity should be restored to less than or equal to 1 degree (CTCAE 5.0, except for hair loss).

8. ECOG score 0-1 points; 9. Expected survival time> 3 months; 10. Sufficient organ function, subjects need to meet the following laboratory indicators:

1. The absolute value of neutrophils (ANC) ≥1.5x109/L when no granulocyte colony-stimulating factor is used in the past 14 days;

2. In the case of no blood transfusion in the past 14 days, platelets ≥100×109/L;

3. In the past 14 days without blood transfusion or erythropoietin, hemoglobin>9g/dL;

4. Total bilirubin≤1.5×upper limit of normal (ULN);

5. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) within ≤2.5×ULN (subjects with liver metastases are allowed to have ALT or AST ≤5×ULN);

6. Serum creatinine ≤1.5×ULN and creatinine clearance rate (calculated by Cockcroft-Gault formula) ≥50ml/min;

7. Good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 times ULN;

8. Normal thyroid function is defined as thyroid-stimulating hormone (TSH) within the normal range. If the baseline TSH is out of the normal range, subjects whose total T3 (or FT3) and FT4 are within the normal range can also be included in the group;

9. Myocardial enzyme spectrum is within the normal range (for example, simple laboratory abnormalities that are judged by the investigator to be of no clinical significance are also allowed to be included in the group); 11. For female subjects of childbearing age, a urine or serum pregnancy test and the result should be negative within 3 days before receiving the first study drug administration (day 1 of cycle 1). If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Women of non-bearing age are defined as at least 1 year after menopause, or have undergone surgical sterilization or hysterectomy; 12. If there is a risk of conception, all subjects (whether male or female) need to adopt a low annual failure rate during the entire treatment period until 120 days after the last study drug administration (or 180 days after the last study drug administration) Less than 1% of contraceptive measures.

Exclusion Criteria:

• Subjects who meet the following criteria cannot be selected for this study:

1. The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC;

2. Non-small cell lung cancer diagnosed as EGFR gene mutation or ALK, ROS1 gene fusion;

3. Subjects who have previously used anti-PD-1, PD-L1 or other immunotherapy and meet the following conditions:

1) The toxicity that caused permanent discontinuation occurred before the termination of immunotherapy; 2) Prior to the administration of the study drug, the toxicity of the previous immunotherapy has not recovered or has not recovered to level 0-1. Asymptomatic and stable control of endocrine toxicity level 2 with appropriate replacement therapy is allowed to enter the group; 3) Adverse events that require additional immunosuppressive agents in addition to corticosteroids, or adverse events that still recur in the use of corticosteroids during previous immunotherapy.

4. Have received the following treatments:

1. Received systemic anti-tumor therapy within 2 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine with anti-tumor indications), etc.;

2. Have received any investigational drug treatment within 4 weeks before treatment;

3. Received large doses of immunosuppressive drugs within 4 weeks before treatment (systemic glucocorticoid exceeding 10mg/day prednisone or its equivalent dose);

4. Received live attenuated vaccine within 4 weeks before treatment (or plan to receive live attenuated vaccine during the study period);

5. Have received major surgery (such as open cavity, thoracotomy, or Kaifu surgery), or unhealed surgical wounds, ulcers or fractures within 4 weeks before treatment.

5. There is clinically uncontrollable pleural effusion/abdominal effusion (subjects who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included in the group); 6. Subjects who have received thoracic radiotherapy of greater than 30 Gy within 6 months before treatment or palliative radiotherapy of 30 Gy or less within 7 days before treatment (allowing palliative treatment of bone lesions or intracranial lesions) Radiation Therapy); 7. An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments; 8. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 9. Before starting treatment, have not fully recovered from toxicity and/or complications caused by any intervention (ie, ≤ Grade 1 or reached baseline, excluding fatigue or hair loss); 10. Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody positive); 11. Untreated active hepatitis B (defined as HBsAg positive and the number of HBV-DNA copies detected at the same time is greater than the upper limit of the normal value of the laboratory department of the research center);

Note: Hepatitis B subjects who meet the following criteria can also be included in the group:

6) Before the first administration, the HBV viral load is less than 1000 copies/ml (200 IU/ml), and the subject should receive anti-HBV treatment during the entire study chemotherapy drug treatment to avoid viral reactivation 7) For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is no need to receive preventive anti-HBV treatment, but close monitoring of virus reactivation is required 12. Active HCV infected subjects (HCV antibody-positive and HCV-RNA level is higher than the lower limit of detection); 13. Live vaccines have been vaccinated within 30 days before the first administration (cycle 1, day 1); Note: It is allowed to receive inactivated virus vaccine for seasonal influenza injection within 30 days before the first administration; however, it is not allowed to receive live attenuated influenza vaccine for intranasal administration.

14. Pregnant or lactating women; 15. There are any serious or uncontrollable systemic diseases, such as:

1. The resting electrocardiogram has major abnormalities in rhythm, conduction or morphology that are severe and difficult to control, such as complete left bundle branch block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;

2. Unstable angina pectoris, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) grade ≥ 2;

3. Myocardial infarction occurred within 6 months before enrollment;

4. Unsatisfactory blood pressure control (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg);

5. A history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or current clinically active interstitial lung disease;

6. Active tuberculosis;

7. There is an active or uncontrolled infection that requires systemic treatment;

8. There is clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction;

9. Liver diseases such as liver cirrhosis, decompensated liver disease, acute or chronic active hepatitis;

10. Poor control of diabetes (fasting blood glucose (FBG)> 10mmol/L);

11. Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantification is confirmed to be greater than 1.0 g;

12. Subjects who have mental disorders and cannot cooperate with treatment; 16. The medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the test results, prevent the subject from participating in the study, or the investigator believes that it is not suitable for inclusion this research.