A Study to Evaluate SHR-1210 in Combination With Famitinib Plus Chemotherapy in Subjects With NSCLC.

Non-squamous Non-small-cell Lung Cancer Clinical Trial

Official title:

A Multi-center, Randomized, Double-blind, Phase III Trial of SHR-1210 in Combination With Famitinib or Placebo Plus Chemotherapy in Subjects With Non-squamous Non-small-cell Lung Cancer.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04619433
• Other study ID #: SHR-1210-III-324
• Status: Recruiting
• Phase: Phase 3
• Start date: February 1, 2021
• Est. completion date: October 15, 2023

Study information

• Verified date: November 2020
• Source: Jiangsu HengRui Medicine Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study is being conducted to evaluate the efficacy and safety of SHR-1210 in combination with Famitinib plus chemotherapy in subjects with NSCLC.

Description:

The study is being conducted to evaluate the efficacy and safety of Camrelizumab in combination with Famitinib plus chemotherapy in subjects with NSCLC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 560
• Est. completion date: October 15, 2023
• Est. primary completion date: December 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Signed Informed Consent Form, male or female, 18-70 years of age.

2. Histologically or cytologically confirmed, Stage IIIB-IV non-squamous NSCLC

3. EGFR mutation and ALK rearrangement status must be negative.

4. No prior system chemotherapy for advanced/metastatic NSCLC.

5. Measurable diseaseas defined by RECIST v1.1.

6. ECOG performance status of 0 or 1.

7. Has a life expectancy of at least 3 months.

8. Adequater organ function.

9. Female subjects of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose, and be willing to use a recognized effective contraceptive measure during the study and within 3 months after the last dose of the study drug; Male subjects with partners of childbearing potential must either be surgically sterilized or agree to take effective contraceptive measures during the study and within 3 months after the last dose of the study drug. Exclusion Criteria: 1? Cancer-Specific Exclusions

1. Other histological types of non-small cell lung cancer.

2. Subjects with carcinomatous meningitis and spinal cord compression.

3. Subjects with untreated central nervous system (CNS) metastasis.

4. Subjects who can be treated with surgical resection or radical radiotherapy.

5. Subjects who previously received anti-PD-1(L1) or CTLA4 monoclonal antibody, VEGF or VEGFR signaling pathway single target/multiple target inhibitor or monoclonal antibodies.

2. Medical history and complications

1. Subjects with any active, known, or suspected autoimmune diseases.

2. Subjects who require systemic corticosteroids prednisone (> 10 mg/day or equivalent) or other immunosuppressants within 14 days prior to the first dose.

3. Subjects who received cancer vaccines or other immunostimulatory anti-cancer agents (interferon, interleukin, thymosin, or immune cell therapy) within 1 month prior to the first dose.

4. Subjects who received anti-cancer TCM within 14 days prior to the first dose.

5. Subjects who are in another clinical study or last participated (last dose) in a clinical study less than 4 weeks (or 5 half-lives of the study drug) from the first dose, whichever is shorter.

6. Subjects who are expected to require other forms of anti-cancer treatment during the study.

7. Subjects who received major surgery within 4 weeks prior to the first dose, non-thoracic radiation therapy > 30 Gy within 4 weeks prior to the first dose, thoracic radiation therapy > 30 Gy within 24 weeks prior to the first dose, or palliative radiation = 30 Gy within 2 weeks prior to the first dose, and failed to recover from the toxicities and/or complications of these interventions to NCI-CTC AE Grade = 1 (except for alopecia and fatigue). Palliative radiotherapy for symptomatic control is permitted, but must be completed within 2 weeks prior to starting the study treatment.

8. Subjects highly suspected of interstitial lung disease, or with conditions that may interfere with the testing or management of suspected treatment-related pulmonary toxicities, or other moderate to severe lung diseases that seriously affect pulmonary function.

9. Subjects with a history of malignant tumors.

10. Subjects with severe cardiovascular disease.

11. Subjectss with hypertension which cannot be well controlled by antihypertensives.

12. Subjects with clinically significant hemorrhage or clear bleeding tendency within 3 month prior to the first dose.

13. Events of arterial/venous thrombosis within 6 months prior to the first dose.

14. Subjects who require long-term anticoagulant therapy with warfarin or heparin.

15. Subjects who require long-term antiplatelet therapy.

16. Significant vascular invasions or a high possibility of significant vascular invasions that may cause bleeding as determined by the investigator during treatment.

17. Subjects with active pulmonary tuberculosis (TB).

18. Subjects with serious infection within 4 weeks prior to the first dose, including but not limited to infective complications, bacteremia, and severe pneumonia that require hospitalization.

19. Subjects who prepare to receive or have previously received tissue/organ transplants.

20. Gastrointestinal disorder or surgical history that may affect the swallowing, digestion, and absorption of the oral drug as determined by the investigator.

21. Subjects who plan to receive or have received live vaccines within 30 days prior to the first dose.

22. Subjects with uncontrolled cancer pain.

3. Physical examination and laboratory tests

1. Known history of human immunodeficiency virus (HIV) seropositive status or acquired immunodeficiency syndrome (AIDS).

2. Active hepatitis B virus or hepatitis C virus infection.

3. Subjects with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

4. Allergies and adverse drug reactions

1. Severe allergic reactions to other monoclonal antibodies.

2. Allergy or intolerance during an infusion.

3. History of severe allergies to pemetrexed, carboplatin, or their premedications.

5. Subjects with mental illness, alcohol abuse, inability to quit smoking, and drug or substance abuse.

6. Based on the investigator's judgment, subjects with a history or current evidence of diseases, treatments, or laboratory abnormalities that may affect study results, interfere with study procedures, or are not in the best interests of the subjects, should be excluded.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-squamous Non-small-cell Lung Cancer

Intervention

Drug:
• Camrelizumab;Pemetrexed and Carboplatin; Famitinib;
Part 1: Drug: Camrelizumab; Pemetrexed; Carboplatin; Famitinib Part 2: Drug: Camrelizumab; Pemetrexed; Carboplatin; Famitinib
• Camrelizumab;Pemetrexed and Carboplatin;Placebo
Part 2: Drug: Camrelizumab; Pemetrexed; Carboplatin; Placebo

Locations

Country	Name	City	State
China	Beijing Cancer Hosipital	Beijing	Beijing
China	Beijing Cancer Hosipital	Beijing	Beijing
China	West China Hospital,Sichuan University	Chengdu	Sichuan
China	Shanghai Lung Hospital	Shanghai	Shanghai
China	Shengjing Hospita of China Medical University	Shenyang	Liaoning
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Hubei Cancer Hospita	Wuhan	Hubei
China	Henan Cancer Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu HengRui Medicine Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1:Serum concentrations of Camrelizumab		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Plasma concentrations of Famitinib		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Area Under the Plasma Concentration Versus Time Curve (AUC) of Famitinib.		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Maximum Concentration (Cmax) of Famitinib.		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Time to Maximum Concentration (Tmax) of Famitinib.		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Half-life (t1/2 z) of Famitinib.		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Apparent Clearance (CL/F) of Famitinib		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 1:Vz/F of Famitinib.		Cycle 2; each cycle is 21 days (up to 42 days)
Primary	Part 2: Progression-free Survival (PFS) as Assessed by BICR according to RECIST 1.1.		up to 24 months
Secondary	Part 1:Objective Response Rate (ORR) as Assessed by investigators		Cycle 2; each cycle is 21 days (up to 42 days)
Secondary	Part 1:Duration of Response (DOR) as Assessed by investigators		Cycle 2; each cycle is 21 days (up to 42 days)
Secondary	Part 1:Progression-free Survival (PFS) as Assessed by investigators		Cycle 2; each cycle is 21 days (up to 42 days)
Secondary	Part 1:Overall Survival (OS).		Up to approximately 60 months
Secondary	Part 2:Overall Survival (OS)		Up to approximately 60 months
Secondary	Part 2:Progression-free Survival (PFS) as Assessed by investigators according to RECIST 1.1.		up to 24 months
Secondary	Part 2:Objective Response Rate (ORR) as Assessed by investigators and BICR according to RECIST 1.1		up to 24 months
Secondary	Part 2:Duration of Response (DOR) as Assessed by investigators and BICR according to RECIST 1.1		up to 24 months
Secondary	Part 2:Disease Control Rate(DCR) as Assessed by investigators and BICR according to RECIST 1.1		up to 24 months
Secondary	Part 2:Number of Participants With Adverse Events and Serious Adverse Event as Assessed by CTCAE v5.0.		up to 24 months