Anti-CTLA-4 Antibody Followed by Anti-PD-1 Antibody in Recurrent or Metastatic NSCLC

Non Small Cell Lung Cancer Clinical Trial

— SEQUENCE  

Official title:

A Phase I Study Evaluating the Safety and Efficacy of CTLA-4 Antibody Ipilimumab Followed by PD-1 Antibody SHR-1210 in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03527251
• Other study ID #: 2018-FXY-032
• Status: Recruiting
• Phase: Phase 1
• Start date: May 15, 2018
• Est. completion date: December 31, 2019

Study information

• Verified date: May 2018
• Source: Sun Yat-sen University
• Contact: Wenfeng Fang, MD
• Phone: 86-15322302066
• Email: fangwf[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Immunotherapy has made rapid progress in melanoma, Hodgkin's lymphoma, non-small cell lung cancer, and bladder cancer, etc. Preclinical data suggested that the use of anti-PD-1 antibody in combination with CTLA-4 receptor blockers may increase antitumor activity. The CheckMate-012 study showed that nivolumab and ipilimumab combination therapy achieved an overall response rate of 43% in unselected patients with non-small cell lung cancer, compared with 23% in the nivolumab monotherapy group; and in the PD-L1 positive subgroup, nivolumab in combination with ipilimumab showed a response rate of 57%, while nivolumab alone was 28%. This showed that the combination therapy of nivolumab and ipilimumab can increase the efficacy, but the adverse events of grade 3 or above of combination therapy reach 37%. The toxic side effects limit the widespread use of nivolumab in combination with ipilimumab therapy.

However, since the action of ipilimumab is limited to the initiation of the immune response (antigen presentation and immune cell activation), and its long half-time of 15.4 days, ipilimumab can used as an induction therapy, following by the PD1 monoclonal antibody. This phase I study is aimed to evaluated the safety and efficacy of CTLA-4 antibody followed by PD-1 antibody in patients with recurrent or metastatic non-small cell lung cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 31, 2019
• Est. primary completion date: December 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >=18 years old, male or female;

• Histologically confirmed locally advanced or metastatic non-small-cell lung cancer;

• At least one systemic chemotherapy regimen for locally advanced or metastatic disease (patients received neoadjuvant chemotherapy, concurrent chemoradiotherapy, or adjuvant chemotherapy within 6 months can be considered as first-line system therapy);

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1;

• At least one measurable lesion according to criteria RECIST v1.1;

• Life expectancy of at least 12 weeks;

• Patient has adequate bone marrow as defined by the following laboratory values:

White blood cell = 3.0 × 109/L Absolute neutrophil count = 1.5 × 109/L Platelets = 75 × 109/L

• Patient has adequate organ function as defined by the following laboratory values:

In absence of liver metastases, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver metastases, ALT and AST should be < 5 × ULN Total serum bilirubin < ULN; or total bilirubin = 3.0 × ULN with direct bilirubin within normal range of the central laboratory in patients with well documented Gilbert's Syndrome Serum creatinine = 1.5 × ULN

• Provide written, informed consent to participate in the study and follow the study procedures;

• Women of childbearing potential must agree and commit to the use of a highly effective non-hormonal method of contraception, ie, intrauterine device, bilateral tubal ligation, vasectomized partner, or abstinence (only when it is the preferred lifestyle of the patient), from the time of informed consent until 28 days after the last dose of the investigational products. Men and their female partners of childbearing potential must agree and commit to use a highly effective method of contraception (ie, any of the above methods or hormonal contraception associated with inhibition of ovulation) while on treatment and for 3 months after last dose of investigational products

Exclusion Criteria:

• Driver gene EGFR, ALK and ROS were positive;

• In presence of active autoimmune disease or a history of autoimmune disease (such as the following, but not limited to: interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism; Patients with hormone replacement therapy can be included; Patients with vitiligo or asthma in childhood have been completely relieved, and no intervention in adults can be included; The subjects who needed medical intervention with bronchial dilation were ineligible;

• Patients are using immunity inhibitors or systemic hormone therapy for immunosuppression purpose (such as prednisone > 10 mg/day), except for local hormone therapy.

• Patients were known to be allergic to macromolecular protein, or any components in ipilimumab or SHR-1210;

• Patients with clinical symptoms of central nervous system metastasis (e.g. brain edema, requirement of hormone intervention, or brain metastases progression);

• Another malignancy within 2 years prior to screening, with the exception of adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell carcinoma or non-melanomatous skin cancer;

• Patients with congenital or acquired immunodeficiency (such as HIV infection), or active hepatitis (HBV DNA=104/ml);

• Any severe and / or uncontrolled medical conditions.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Ipilimumab
Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.
• SHR-1210
Patients received two doses of intravenous ipilimumab (at a dose of 1 mg per kilogram of body weight) every 3 weeks, following by intravenous SHR-1210 (at a fixed dose of 200mg) every 2 weeks.

Locations

Country	Name	City	State
China	Cancer Center of Sun-Yat Sen University (CCSYSU)	GuangZhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety in the treatment of ipilimumab followed by SHR1210	Adverse events occurring up to 30 days after the last dose of ipilimumab or SHR1210 are evaluated and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0.	24 months
Secondary	Overall Response Rate (ORR)	ORR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Secondary	Clinical Benefit Response (CBR)	CBR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Secondary	Progression-free Survival (PFS)	PFS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Secondary	Overall survival (OS)	OS as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Secondary	Duration of response (DOR)	DOR as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks
Secondary	Time To Progression (TTP)	TTP as measured in accordance with the Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1	Up to 4 weeks