The Efficacy and Safety of the Bispecific Anti-PD-1/PD-L1 Antibody IBI318 Combined with Lenvatinib in NSCLC.

NCT04777084 | Recruiting Phase 2

• 1 other identifier: LIVE
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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IBI318 combined with lenvatinib until the disease progresses, death, toxicity is intolerable, informed consent is withdrawn, new anti-tumor therapy is started, or the treatment is terminated for other reasons specified in the plan.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 12 weeks ORR

  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.

  1 year

Secondary Outcomes (6)

• PFS

  1 year

• DCR

  1 year

• DOR

  1 year

• OS

  1 year

• BOR

  1 year

Study Arms (3)

Cohort A

EXPERIMENTAL

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.

Drug: IBI318

Cohort B

EXPERIMENTAL

Cohort B is the efficacy and safety of advanced NSCLC with EGFR-sensitive mutation /ALK fusion after EGFR-TKI /ALK-TKI treatment resistance.

Drug: IBI318

Cohort C

EXPERIMENTAL

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.

Drug: IBI318

Interventions

IBI318 DRUG

IBI318, 300 mg, administered by intravenous infusion on the first day of each cycle, 1 cycle every 2 weeks (Q2W), continuous medication; lenvatinib 8 mg, orally, continued medication until disease progression, death, toxicity is intolerable, Withdrawal of informed consent, start a new anti-tumor treatment or terminate the treatment for other reasons specified in the plan, the maximum use time is 2 years.

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• There is no T790M mutation in 20 exon after the failure of previous one or two generations of EGFR-TKI (including gefitinib, erlotinib, icotinib and afatinib);
• The 20 exon T790M mutation occurred after the treatment failure of the first or second generation EGFR-TKI monotherapy (including gefitinib, erlotinib, icotinib, and afatinib, etc.), and disease progression recurred after treatment with osimertinib or other third generation EGFR-TKI;
• Failure of prior osimertinib or other third-generation EGFR-TKI therapy as first-line therapy (regardless of EGFR T790M mutation status);
• Those who are allowed to receive neoadjuvant/adjuvant targeted therapy in the early stage and develop drug resistance after subsequent adjuvant targeted therapy, and their drug resistance status meets one of the three requirements of appeal.

You may not qualify if:

• 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;
• 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 0-1. 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.); 4. Have received the following treatments:
• Received systemic anti-tumor therapy within 2 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine with anti-tumor indications), etc.;
• Previously received lenvatinib, bevacizumab, anlotinib monotherapy, or in combination with anti-PD-1 / PD-L1 drugs
• Have received any investigational drug treatment within 4 weeks before treatment;
• Received large doses of immunosuppressive drugs within 4 weeks before treatment (systemic glucocorticoid exceeding 10mg/day prednisone or its equivalent dose);
• Received live attenuated vaccine within 4 weeks before treatment (or plan to receive live attenuated vaccine during the study period);
• Have received major surgery (such as open cavity, thoracotomy, or Kaifu surgery), or unhealed surgical wounds, ulcers or fractures within 4 weeks before treatment.
• \. Clinically significant cardiovascular damage occurred within 12 months of the first dose of study treatment.

Sponsors & Collaborators

• Hunan Province Tumor Hospital: lead

Study Sites (1)

Hunan Cancer hospital

Changsha, Hunan, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Study Officials

• Yongchang Zhang, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yongchang Yongchang, MD

CONTACT

+8613873123436; zhangyongchang@csu.edu.cn

Nong Yang, MD

CONTACT

+8613055193557; yangnong0217@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Deputy Director of Thoracic Oncology Department

Study Record Dates

• First Submitted: February 27, 2021
• First Posted: March 2, 2021
• Study Start: August 1, 2021
• Primary Completion: December 30, 2024
• Study Completion: December 25, 2025
• Last Updated: March 5, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)