PD-L1 Inhibitor Rechallenge After PD-1 Immunotherapy for Patients With Solid Tumor Beyond Lung Cancer

Efficacy and Safety of PD-L1 Inhibitor in Patients With Advanced Solid Tumors Beyond Lung Cancer: a PhaseⅠB Clinical Study

Anti-PD-L1 immune checkpoint inhibitor, is approved for the treatment of patients with unresectable, Stage III NSCLC whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy, or as first-line treatment of patients with ES-SCLC in combination with etoposide and either carboplatin or cisplatin in China. The clinical data regarding the PD-L1 inhibitor in other solid tumors are limited.Investigators would observe and analyze the effectiveness and safety of PD-L1 inhibitor for patients with advanced - solid tumors beyond lung cancer after muti-line therapy to explore the synergistic effect of PD-L1 inhibitor rechallenge after PD-1immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Efficacy; Safety
• Intervention / Treatment: Drug: PD-L1 inhibitor

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiaochun Zhang, Prof; Phone Number: 086053282913271; Email: zxcgcp@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed Informed Consent Form
• Ability to comply with protocol
• Aged ≥ 18 years
• Histologically documented advanced solid tumor beyond lung cancer
• Disease progression during or following at least one line treatment containing PD-1 immunotherapy.
• Measurable disease, as defined by RECIST v1.1
• ECOG performance status of 0 or 1
• Life expectancy ≥ 12 weeks
• Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment:

ANC ≥ 1.5 × 109/L (without granulocyte colony-stimulating factor support within 2 weeks of laboratory test used to determine eligibility) WBC counts > 2.5 × 109/L and < 15 × 109/L Lymphocyte count ≥ 0.5 × 109/L Serum albumin ≥ 2.5 g/dL Platelet count ≥ 100 × 109/L (without transfusion within 2 weeks of laboratory test used to determine eligibility) Hemoglobin ≥ 9.0 g/dL Patients may be transfused or receive erythropoietic treatment to meet this criterion.

Liver function tests meeting one of the following criteria:

AST or ALT ≤ 2.5 × upper limit of normal (ULN), with alkaline phosphatase

≤ 2.5 × ULN or AST and ALT ≤ 1.5 × ULN in conjunction with alkaline phosphatase > 2.5 × ULN Serum bilirubin ≤ 1.5 × ULN Patients with known Gilbert's disease who have serum bilirubin level ≤ 3 × ULN may be enrolled. INR and aPTT ≤ 1.5 × ULN This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose for at least 1 week prior to randomization. Creatinine clearance ≥ 30 mL/min Cockcroft-Gault, Chronic Kidney Disease Epidemiology Collaboration, or Modification of Diet in Renal Disease formulas may be used for creatinine clearance calculation. Note that 24-hour urine collection is not required but is allowed.

Exclusion Criteria:

• Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Uncontrolled hypertension
• Autoimmune disease
• Had undergone a serious anaphylactic reaction in previous immunotherapy

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: PD-L1 rechallenge	Drug: PD-L1 inhibitor; Enrolled patients received durvalumab/ Atezolizumab plus chemotherapy or target therapy treatment (durvalumab,1000mg，iv, d1, 21day as a cycle; Atezolizumab,1200mg iv, d1, 21day as a cycle.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	progression-free survival	From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months
DCR	Disease Control Rate	At the end of Cycle 3 (each cycle is 21 days)".

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	overall survival	From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
AE	adverse event caused by the treatment	hrough study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: The Affiliated Hospital of Qingdao University
• Investigators: Principal Investigator: Xiaochun Zhang, Prof, The Affiliated Hospital of Qingdao University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: April 6, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 6, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immune Checkpoint Inhibitors
• Other Study ID Numbers: PDL1-BEY-LUNG

Drug and device information, study documents

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