A Prospective, Multi-cohort Clinical Research of Efficacy and Safety of Bispecific Anti-PD-1 / PD-L1 Antibody IBI318 Combined with Lenvatinib in the Treatment of Advanced NSCLC
Overview
- Phase
- Phase 2
- Intervention
- IBI318
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Hunan Province Tumor Hospital
- Enrollment
- 120
- Locations
- 1
- Primary Endpoint
- 12 weeks ORR
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The study is a prospective multi-cohort clinical study. Cohort A is evaluating the efficacy and safety of IBI318 in combined with lenvatinib in advanced NSCLC patients who had failed first-line PD-1/PD-L1 inhibitor therapy. Cohort B is the efficacy and safety of advanced NSCLC with EGFR-sensitive mutation /ALK fusion after EGFR-TKI /ALK-TKI treatment resistance. Cohort C is the efficacy and safety of first-line treatment of advanced NSCLC with negative PD-L1 expression and EGFR, ALK, and ROS1 wild-type. 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IBI318 combined with lenvatinib until the disease progresses, death, toxicity is intolerable, informed consent is withdrawn, new anti-tumor therapy is started, or the treatment is terminated for other reasons specified in the plan.
Detailed Description
The study is a prospective multi-cohort clinical study. Cohort A is evaluating the efficacy and safety of IBI318 in combined with lenvatinib in advanced NSCLC patients who had failed first-line PD-1/PD-L1 inhibitor therapy. Cohort B is the efficacy and safety of advanced NSCLC with EGFR-sensitive mutation /ALK fusion after EGFR-TKI /ALK-TKI treatment resistance. Cohort C is the efficacy and safety of first-line treatment of advanced NSCLC with negative PD-L1 expression and EGFR, ALK, and ROS1 wild-type. 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IBI318 combined with lenvatinib until the disease progresses, death, toxicity is intolerable, informed consent is withdrawn, new anti-tumor therapy is started, or the treatment is terminated for other reasons specified in the plan. During the treatment, RECIST v1.1 was used for clinical tumor imaging evaluation, once every 6 weeks; after 24 weeks of medication, evaluation can be done every 8 weeks. Subjects receiving IBI318 combined with lenvatinib have the first evidence of imaging PD according to RECIST v1.1. If the subject is clinically stable, there is no evidence of rapid imaging progress, and the investigator assesses that it can continue from the study If the patient is benefited from the drug, the subject can continue the current study treatment, and the imaging evaluation must be repeated at least 6 weeks (± 7 days) later for confirmation. If PD is confirmed by re-assessment, the subject should stop the study treatment; if PD is not confirmed, the study treatment will continue, and the assessment will be carried out at the time point of the imaging examination plan specified in the plan until the PD is confirmed by imaging.
Investigators
Yongchang Zhang
Professor, Deputy Director of Thoracic Oncology Department
Hunan Province Tumor Hospital
Eligibility Criteria
Inclusion Criteria
- •Eligible subjects selected for this study must meet all of the following criteria:
- •Sign written informed consent before implementing any trial-related procedures;
- •Age ≥18 years old and ≤75 years old;
- •No limit on the gender;
- •Cohort A: histological or cytological confirmed locally advanced (IIIB-IIIC) or metastatic (stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint Committee on the American Classification of Cancer, TNM Lung cancer stage 8) without EGFR gene sensitive mutations, ALK gene fusion or ROS1 gene fusion confirmed by histological specimens, Relapse after failure of first-line anti-PD-1 /PD-L1 antibody therapy, as follows:
- •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;
- •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);
- •Disease progression confirmed by imaging studies occurred during or after the most recent treatment.
- •Cohort B: histological or cytological confirmed locally advanced (IIIB-IIIC) or metastatic (stage IV) NSCLC (International Association for the Study of Lung Cancer and Joint Committee on the American Classification of Cancer, TNM Lung cancer stage 8) with histologically confirmed EGFR-sensitive mutations or ALK fusion, Relapse after failure of anti-EGFR-TKI or ALK-TKI therapy, as follows:
- •In patients with EGFR-tKI sensitive mutations, the specific history of previous EGFR-TKI treatment can be one of the following:
Exclusion Criteria
- •Subjects who meet the following criteria cannot be selected for this study:
- •The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC;
- •There is imaging evidence of tumor voids, tumor inclusion or invasion of large vessels. In addition, the proximity of the tumor to the large blood duct should be considered and the risk of severe bleeding associated with tumor shrinkage/necrosis after lenvatinib treatment should be excluded. (The large vessels in the chest include the main pulmonary artery, left pulmonary artery, right pulmonary artery, 4 pulmonary veins, superior vena cava, inferior vena cava and aorta);
- •To cohort A: subjects who have previously used anti-PD-1, PD-L1 or other immunotherapy and meet the following conditions:
- •The toxicity that caused permanent discontinuation occurred before the termination of immunotherapy;
- •Prior to the administration of the study drug, the toxicity of the previous immunotherapy has not recovered or has not recovered to level 0-
- •Asymptomatic and stable control of endocrine toxicity level 2 with appropriate replacement therapy is allowed to enter the group;
- •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.
- •To cohort B and C: Prior treatment: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T-cell receptor (including but not limited to CTLA-4, OX-40, CD137, etc.); Anti-pd-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T cell receptor (including but not limited to CTLA-4, OX-40, CD137, etc.);
- •Have received the following treatments:
Arms & Interventions
Cohort A
Cohort A is evaluating the efficacy and safety of IBI318 in combined with lenvatinib in advanced NSCLC patients who had failed first-line PD-1/PD-L1 inhibitor therapy.
Intervention: IBI318
Cohort B
Cohort B is the efficacy and safety of advanced NSCLC with EGFR-sensitive mutation /ALK fusion after EGFR-TKI /ALK-TKI treatment resistance.
Intervention: IBI318
Cohort C
Cohort C is the efficacy and safety of first-line treatment of advanced NSCLC with negative PD-L1 expression and EGFR, ALK, and ROS1 wild-type.
Intervention: IBI318
Outcomes
Primary Outcomes
12 weeks ORR
Time Frame: 1 year
Defined as the proportion of subjects achieving a complete remission (CR) or partial remission (PR) at around 12 weeks after the start of study treatment among all subjects.
Secondary Outcomes
- OS(1 year)
- PFS(1 year)
- DCR(1 year)
- DOR(1 year)
- adverse events (safety)(1 year)
- BOR(1 year)