PD-1 Combined With Bevacizumab and PCSK-9 Inhibitor in Patients With Advanced NSCLC Who Have Progressed After Anti- PD- 1/L1 Therapy

NCT07014215 | Not Yet Recruiting Phase 2

• 1 other identifier: 2024-ethics-134
• Study Type: interventional
• Target: 52
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluated the sintilimab combination of bevacizumab and tafolecimab in NSCLC patients who have previously been treated with anti- PD- 1/ligand (L)1 and acquired resistance. The patients were assigned to receive sintilimab(200mg Q3W) in combination with bevacizumab(7.5mg/kg Q3W) and tafolecimab(600 mg Q6W). The primary endpoints of the study were progression- free survival (PFS) assessed by RECISTv1.1 , while secondary endpoints included objective response rate (ORR), and overall survival (OS) and safety.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer); Resistance to Immunotherapy

Outcome Measures

Primary Outcomes (1)

• PFS

  The time from the beginning of treatment to the time when the disease progresses or the patient dies from any cause

  24months

Secondary Outcomes (3)

• ORR

  24months

• OS

  24months

• AE

  24months

Study Arms (1)

Experimental arm

EXPERIMENTAL

Drug: Sintilimab combined with bevacizumab and tafolecimab

Drug: Sintilimab combined with Bevacizumab and tafolecimab

Interventions

Sintilimab combined with Bevacizumab and tafolecimab DRUG

Patients who met the inclusion criteria were treated with sintilimab(200mg Q3W) combined with Bevacizumab(7.5mg/kg Q3W) and tafolecimab(600mg Q6W) until disease progression or intolerable adverse reactions or death(up to 24 months)

Experimental arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Sign written informed consent before implementing any experimental procedures
• \. Age ≥ 18 years old and ≤ 80 years old
• \. Histological or cytological confirmation of locally advanced (IIIB-IIIC), metastatic or recurrent (stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint Committee on Cancer Classification 9th edition TNM lung cancer staging)
• \. Failure after previous treatment with PD - (L) 1 inhibitors (alone or in combination with another systemic therapy) (CR, PR, SD\>6 months)
• \. Previously not receiving anti angiogenic drug treatment
• \. Confirmed by histological specimens that there are no EGFR gene sensitive mutations, ALK gene fusion mutations, ROS1 gene mutations, or RET gene mutations
• \. According to the criteria for evaluating the efficacy of solid tumors (RECIST v1.1 version), there should be at least one measurable lesion on imaging. If the lesion located within the previous radiation field is confirmed to have progressed, it can be considered a measurable lesion
• \. Subjects with brain metastases who are asymptomatic or have stable symptoms after local treatment are allowed to be enrolled, as long as they meet the following conditions:
• Measurable lesions outside the central nervous system
• No central nervous system symptoms or no worsening of symptoms within at least 2 weeks
• No need for glucocorticoid treatment, or discontinuation of glucocorticoid treatment within 7 days prior to the first dose, or stable and reduced glucocorticoid dosage to below 10mg/day of prednisone (or equivalent dose) within 7 days prior to the first dose
• \. Subjects are allowed to receive palliative radiation therapy (including cranial radiation therapy for symptomatic brain metastases), provided that the radiation therapy is completed at least one week before enrollment and the radiation related toxicity has recovered to less than or equal to degree 1 (CTCAE 5.0, except for hair loss)
• \. ECOG rating 0-1 points
• \. Expected survival time\>3 months
• \. Adequate organ function, subjects must meet the following laboratory indicators:

You may not qualify if:

• \. Pathological diagnosis of small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC
• \. The patient has received first-line or more PD - (L) 1 inhibitor monotherapy or combination chemotherapy treatment
• \. Received the following treatments:
• Received systemic anti-tumor therapy within 3 weeks prior to treatment, such as chemotherapy, targeted therapy, immunotherapy (including herbal therapy with anti-tumor indications), etc
• Received any investigational drug treatment within 4 weeks prior to treatment
• Received high doses of immunosuppressive drugs (systemic corticosteroids exceeding 10mg/day, prednisone or its equivalent) within 4 weeks prior to treatment
• Received attenuated live vaccine within 4 weeks prior to treatment (or planned to receive attenuated live vaccine during the study period)
• Has undergone major surgery (such as open cavity, thoracotomy, or Kaifu surgery) within 4 weeks before treatment, or has unhealed surgical wounds, ulcers, or fractures
• \. There is clinically uncontrollable pleural/peritoneal effusion (subjects who do not require drainage or have no significant increase in effusion after stopping drainage for 3 days can be enrolled)
• \. Subjects who have received chest radiation therapy greater than 30 Gy within the 6 months prior to treatment or palliative radiation therapy with a dose of 30 Gy or less within the 7 days prior to treatment (palliative radiation therapy for bone lesions or intracranial lesions is allowed)
• \. Within 2 years prior to the first administration, there has been an active autoimmune disease requiring systemic treatment (such as the use of disease relieving drugs, corticosteroids, or immunosuppressants). Alternative therapies (such as thyroid hormone, insulin, or physiological glucocorticoids used for adrenal or pituitary insufficiency) are not considered systemic treatments
• \. Known allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation
• \. Individuals known to be allergic to the active ingredients or excipients of the study drug
• \. Before starting treatment, if there has been no sufficient recovery from toxicity and/or complications caused by any intervention measures (i.e. ≤ grade 1 or baseline, excluding fatigue or hair loss)
• \. Known history of human immunodeficiency virus (HIV) infection (i.e. HIV 1/2 antibody positive)

Sponsors & Collaborators

• Anhui Provincial Cancer Hospital: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Zhihong Zhang

CONTACT

0551-65327766; zhangzhihope2022@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: chief physician

Study Record Dates

• First Submitted: May 21, 2025
• First Posted: June 10, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2029
• Last Updated: June 10, 2025

Record last verified: 2025-01