Study of Chemotherapy and PD-1 Inhibitor Combination With Anti-angiogenesis to Treat Elderly Lung Cancer

Phase I Clinical Study of Tislelizumab in Combination With Bevacizumab and Pemetrexed for the First-line Treatment of Advanced Non-squamous Non-small Cell Lung Cancer in Elderly Patients

This single-center, open-label, phaseⅠstudy is to evaluate the efficacy of Tislelizumab in combination with Bevacizumab and Pemetrexed for the first-line treatment of advanced Non-squamous Non-small Cell lung cancer in Elderly Patients

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tislelizumab; Drug: Pemetrexed; Drug: Bevacizumab

Detailed Description

Patients received Bevacizumab, 7.5mg/kg d1, Pemetrexed, 500mg/m2, d1 and Tislelizumab 200mg, d4, Q3W, for 4 cycles; then Tislelizumab 200mg, d1 Q3w and Bevacizumab 7.5mg/kg d1 Q3W, maintenance treatment for 2 years.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects who must meet all the following criteria should be selected:

1. Agree to participate in this trial and sign written informed consent form.
2. Male or female, age ≥ 65 years.
3. Expected survival time ≥ 3 months and able to be followed-up.
4. Stage IIIB/IIIC/IV non-squamous NSCLC patients without previous systemic therapy (according to AJCC8th) or patients with stage IIIB/IIIC/IV non-squamous NSCLC who have relapsed after surgery (if adjuvant therapy was administered, more than 6 months of drug discontinuation is required).
5. Without EGFR mutation and ALK and ROS1 fusion genes.
6. Patients can not receive concurrent chemoradiothrapy after multidisciplinary consultation and discussion.
7. At least one measurable tumor indicator along with a lesion with a maximum diameter of ≥ 1 cm (diagnosed by imaging, e.g., CT, MRI, ECT).
8. ECOG PS 0-1 within 7 days before enrollment.
9. Within 14 days prior to the start of treatment, laboratory results of routine blood, liver and kidney function and hormone levels meet the following criteria: platelets (PLT) ≥ 100 × 109/L, neutrophils (ANC) ≥ 1.5 × 109/L, hemoglobin (HGB) ≥ 90 g/L, aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (≤ 5 × ULN for liver metastases), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, and alanine aminotransferase (ALT) ≤ 1.5 × ULN. × ULN), alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN for liver metastases), total bilirubin (TIBC) ≤ 1.5 × ULN, serum creatinine (CR) ≤ 1.25 × ULN; cortisol and thyroid function are in the normal range.
10. Toxic effects of prior chemotherapy have resolved to grade 1 or less (except alopecia). Subjects must have recovered from toxicity or complications of these interventions if they have received major surgical treatment or > 30Gy of radiation therapy, i.e., they are still eligible for enrollment after 6 months.

Exclusion Criteria:

Subjects who meet any of the following criteria could not participate in this study:

1. Received bevacizumab and/or pemetrexed within 6 months prior to the first dose of study drug.
2. Other malignant tumors with disease progression or requiring aggressive treatment within 5 years of enrollment. Exceptions included early-stage tumors (carcinoma in situ or stage I tumors) that received radical treatment, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or carcinoma in situ of the breast that received potentially radical treatment.
3. Have had an allogeneic tissue/organ transplant.
4. Participating or have participated in investigational drug therapy within 4 weeks prior to the first dose of the trial.
5. Receiving systemic hormone therapy or are receiving any other form of immunosuppressive therapy (except docetaxel pretreated glucocorticoids) within 14 days prior to the first dose of the experimental treatment.
6. Received anti-tumor monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or major surgical procedure within 1 month prior to the first use of study drug; received chest radiation therapy greater than 30 Gy within 6 months prior to the first use of study drug; received chest radiation therapy at 30 Gy or less within 1 month prior to the first use of study drug.
7. Prior treatment with other PD-1 antibodies and other immunotherapy targeting PD-1/PD-L1.
8. Active autoimmune disease requiring systemic therapy (e.g., use of disease-relieving drugs, corticosteroids, or immunosuppressants) within the past 2 years Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic therapy.
9. Having congenital or acquired immune deficiency (e.g., HIV-infected patients), active hepatitis B (HBV-DNA ≥ 2.5 x 10^3 copies/ml), or hepatitis C (positive for hepatitis C antibodies and HCV-RNA above the lower limit of detection for the assay).
10. Patients who have received live vaccine within 4 weeks prior to the first administration of study drug are permitted to receive inactivated viral vaccine for seasonal influenza, administered by injection, but not live attenuated influenza vaccine administered via the nose.
11. Patients with known active central nervous system (CNS) metastases and/or cancerous meningitis. Subjects who have had treatment for brain metastases may also participate in this study provided that the subject is stable (no evidence of progression for at least 4 weeks and all neurological symptoms have returned to baseline levels as determined by MRI prior to the first dose), has no evidence of new or expanding brain metastases, and has not used hormone therapy for at least 3 days prior to study dosing.
12. Bleeding tendency, high bleeding risk, or coagulopathy with a history of thrombotic disease within 6 months and/or hemoptysis within 3 months; being treated with full doses of oral and/or parenteral anticoagulants and thrombolytics (prophylactic anticoagulation is allowed); having used aspirin or other non-steroidal anti-inflammatory drugs that inhibit platelet function within 10 days; and CT/MRI imaging showing tumor encapsulation or invasion of the lumen of large blood vessels.
13. Poorly controlled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg) and patients with prior hypertensive crisis and hypertensive encephalopathy; severe cerebrovascular disease.
14. Non-healing wounds, peptic ulcers in active phase, tracheo-esophageal fistulas, gastrointestinal perforations and intra-abdominal abscesses within 6 months.
15. Have an active infection that requires systemic treatment via Intravenous injection.
16. Have mental illness or other condition, such as uncontrolled heart or lung disease, diabetes mellitus, etc., that prevents cooperation with study treatment and monitoring requirements.
17. History of interstitial lung disease.
18. Patients with moderate to heavy smoking need to quit smoking for more than 1 month.
19. Known allergy to any of the components of the study drug.
20. Patients who are regular users of any drug (including "recreational" use) or have recent history (within 1 year) of substance abuse (including alcohol) when signing the informed consent form.
21. Poor compliance and inability to cooperate with the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tislelizumab+Bevacizumab+Pemetrexed; Bevacizumab，7.5mg/kg，d1; Pemetrexed，500mg/m2，d1; Tislelizumab，200mg，d4; Q3W for 4 cycles; Maintenance treatment ： Tislelizumab，200mg，d1; Bevacizumab，7.5mg/kg，d1; Q3W for 2 years	Drug: Tislelizumab; Tislelizumab intravenous infusion 200mg d4; Other Names: PD-1 inhibitor; Drug: Pemetrexed; Pemetrexed intravenous infusion 500mg/m2 d1; Other Names: Chemotherapy; Drug: Bevacizumab; Pemetrexed intravenous infusion 7.5mg/kg，d1; Other Names: Anti-angiogenesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate	ORR was calculated by the percentage of patients with a confirmed complete (CR) or partial response (PR).	approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Time from the first use of the study drug to the death of the subject	approximately 3 years
Progression-free survival	Progression-free survival is defined as the time from the start of treatment to the first documentation of disease progression or death from any cause, whichever occurs first according to RECIST 1.1.	approximately 2 years
Duration of response	Duration of response is defined as the time from the first recording of evidence of CR or PR until disease progression (according to RECIST 1.1) or death from any cause, whichever occurs first	approximately 2 years
Health-related quality of life	Measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Core 30 (EORTC QLQ-C30) as presented in participants-reported outcomes.Scale construct including to assess Global health status/QoL with range from minimum scores 1 as worse outcome and maximum scores 7 as higher values represent a better; Physical functioning, Role functioning, Emotional functioning, Cognitive functioning, Social functioning, Fatigue, Nausea and vomiting, Pain Dyspnoea, Insomnia, Appetite loss, Constipation, Diarrhoea and Financial difficulties with range from maximum scores 4 as worse outcome and from minimum scores 1 as higher values represent a better.	approximately 2 years
Safety and tolerance	Incidence of Treatment-Emergent Adverse Events	approximately 2 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 1, 2022
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: January 28, 2022
• First Submitted That Met QC Criteria: March 1, 2022
• First Posted (Actual): March 10, 2022

Study Record Updates

• Last Update Posted (Actual): July 13, 2022
• Last Update Submitted That Met QC Criteria: July 11, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Bevacizumab; Pemetrexed; Immune Checkpoint Inhibitors
• Other Study ID Numbers: CCICC-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No