Clinical trial NCT05203276: Envafolimab Combined With Endostar in the First-line Treatment of Advanced NSCLC
Official title: A Prospective, Multi-center, Single-arm Exploratory Clinical Study of Envafolimab Combined With Endostar in the First-line Treatment of Driver Gene-negative Advanced Non-small Cell Lung Cancer With PD-L1 Positive Expression
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lung Neoplasms
Keywords: Envafolimab
Endostar
NSCLC
PD-L1
Lead sponsor: The First People's Hospital of Lianyungang
Sponsor class: OTHER
First posted: 2022-01-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of envafolimab combined with endostar in the first-line treatment of advanced Non-small Cell Lung Cancer With PD-L1 positive expression

Detailed description: Endostar indication: ENDOSTAR + NP chemotherapy regimen is used to treat Stage III/IV NSCLC patients either untreated or pretreated. This indication is based on a completed multi-center Phase III clinical trial.

Envafolimab indication: Envolimab is the world's first subcutaneous injection of PD-L1 monoclonal antibody.Suitable for adult patients with advanced solid tumors with unresectable or metastatic microsatellite highly unstable (MSI-H) or mismatch repair gene defects (dMMR).

Eligibility criteria: Inclusion Criteria:

1. The subject voluntarily joins the study, can complete the signing of the informed consent form, and has good compliance;
2. Age from 18 to 80 years old (when signing the informed consent form), both male and female;
3. According to the 8th edition of the TNM staging classification of lung cancer by the International Association for the Research of Lung Cancer and the American Joint Committee on Cancer Classification, the driver gene (EGFR/ALK/ROS1) is negative and untreated patients with stage IIIB to IV NSCLC;
4. Archived tumor tissue samples or newly obtained (without anti-tumor treatment since the biopsy) core or tumor lesions (not receiving radiotherapy) excised biopsy tissue have been provided. Formalin-fixed and paraffin-embedded (FFPE) tissue blocks are better than sections. The newly obtained biopsy tissue is better than the archived tissue, and the tissue samples are tested by immunohistochemistry for PD-L1 ≥ 1%;
5. According to the evaluation criteria for the efficacy of solid tumors (RECIST Version 1.1), there is at least one imaging measurable lesion; that is, in CT or MRI detection, the longest diameter of a single lesion is ≥10mm, or the lymph node is pathologically enlarged, and a single lymph node is scanned by CT Short diameter ≥15mm;
6. The Eastern Cooperative Oncology Group (ECOG) performance status score is 0-1;
7. The expected survival period is ≥3 months;
8. Newly treated patients who have not received systematic anti-tumor therapy, including radiotherapy and chemotherapy, targeted and immunotherapy, or patients who relapse after follow-up after adjuvant chemotherapy for more than 6 months;
9. With sufficient organ and bone marrow function, the laboratory test values within 7 days before entry into the group meet the following requirements (no blood components, cell growth factors, albumin and other corrective treatment drugs are allowed within the first 14 days of obtaining laboratory tests ),details as follows:

1) Blood routine: absolute neutrophil count (ANC) ≥1.5×109/L, platelet (PLT) ≥75×109/L, hemoglobin (HGB) ≥90 g/L (no blood transfusion or no red blood cells within 14 days) Genin-dependent); 2) Liver function: serum total bilirubin (TBIL) ≤2 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤5 times ULN, serum Albumin ≥28 g/L; Alkaline phosphatase (ALP) ≤5×ULN; 3) Renal function: Serum creatinine (Cr) ≤1.5×ULN, or creatinine clearance ≥50 mL/min (using the standard Cockcroft-Gault formula): urine routine results show urine protein \<2+; urine routine testing at baseline Patients who show urine protein ≥2+ should be collected for 24 hours and the quantification of 24-hour urine protein should be less than 1g; 4) Coagulation function: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN; if the subject is receiving anticoagulation therapy, as long as the INR is within the intended use range of anticoagulant drugs; 10. For female subjects of childbearing age, a urine or serum pregnancy test should be performed 3 days before receiving the first study drug administration and the result is negative; 11. It is necessary to provide tissue samples for biomarker (such as PD-L1) analysis, preferably newly obtained tissues. Patients who cannot provide newly obtained tissues can provide 3-5μm-thick paraffin sections of tissues that are archived and saved within 2 years before enrollment. 5-8 sheets.

Exclusion Criteria:

1. Imaging (CT or MRI) shows that the tumor has invaded large blood vessels or those who are judged to be very likely to invade important blood vessels and cause fatal hemorrhage during the follow-up study;
2. Currently participating in interventional clinical research treatment, or receiving treatment with other research drugs or research devices within 4 weeks before the first administration;
3. Received Chinese patent medicines with anti-tumor indications or immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first administration, or received major surgery within 3 weeks before the first administration;
4. There are active hemoptysis, active diverticulitis, abdominal abscess, gastrointestinal obstruction and peritoneal metastasis that require clinical intervention;
5. Regardless of the severity, patients with any signs of bleeding or medical history; patients with any bleeding or bleeding event ≥ CTCAE level 3 within 4 weeks before enrollment, unhealed wounds, ulcers or fractures;
6. Grade III-IV congestive heart failure (New York Heart Association classification), poorly controlled and clinically significant arrhythmia;
7. Any arterial thrombosis, embolism or ischemia, such as myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, occurred within 6 months before being selected for treatment;
8. Known to have allergic reactions to the drug in this study;
9. Patients who require long-term systemic use of corticosteroids. Patients who require intermittent use of bronchodilators, inhaled corticosteroids, or local injections of corticosteroids due to COPD and asthma can be included in the group;
10. Symptomatic central nervous system metastasis. Patients with asymptomatic brain metastases or brain metastases with stable symptoms after treatment can participate in this study as long as they meet all the following criteria: there are measurable lesions outside the central nervous system; no midbrain, pons, cerebellum, meninges, Medulla oblongata or spinal cord metastasis; maintain a clinically stable state for at least 2 weeks; stop hormone therapy 3 days before the first dose of study drug;
11. There is an active infection that needs to be treated or systemic anti-infective drugs have been used within one week before the first administration;
12. 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);
13. Known human immunodeficiency virus (HIV) infection history (ie HIV 1/2 antibody positive);
14. Untreated active hepatitis B (defined as HBsAg positive and the number of copies of HBV-DNA 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:

1. The HBV viral load before the first administration is less than 1000 copies/ml (200 IU/ml), and the subject should receive anti-HBV treatment during the entire study chemotherapy drug treatment period to avoid viral reactivation;
2. 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.

15. Active HCV infected subjects (HCV antibody-positive and HCV-RNA level is higher than the lower limit of detection); 16. Live vaccine has 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 within 30 days before the first administration; however, it is not allowed to receive live attenuated influenza vaccine for intranasal administration.

17. Pregnant or lactating women; 18. The medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the test results, prevent the subjects from participating in the study, or the investigator believes that it is not suitable for inclusion in the group. The investigator believes that there are other potential risks and is not suitable for participation this research.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: up to 24 months
measure: Number of participants with adverse events as a measure of safety and tolerability
timeFrame: up to 24 months
Secondary outcomes:
measure: PFS
timeFrame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months
measure: DCR
timeFrame: Each 42 days up to intolerance the toxicity or PD (up to 24 months)
measure: OS
timeFrame: From randomization until death (up to 24 months)
measure: DOR
timeFrame: Each 42 days up to intolerance the toxicity or PD (up to 24 months)
Other outcomes:
Locations:
city: Lianyungang
country: China
facility: The First People'S Hospital of Lainyungang
state: Jiangsu
Study officials:
affiliation: The First People's Hospital of Lianyungang
name: Xiaodong Jiang, Doc
role: STUDY_CHAIR
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