Sintilimab ± IBI305 Plus Chemotherapy (Pemetrexed + Cisplatin) for EGFRm + Locally Advanced or Metastasis Non-Squamous NSCLC Patients After EGFR-TKI Treatment Failure

Non-Squamous Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Randomized, Double-blind, Multi-center, Phase III Clinical Study Assessing the Efficacy and Safety of Sintilimab ± IBI305 Combined With Pemetrexed and Cisplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (ORIENT-31)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03802240
• Other study ID #: CIBI338A301
• Status: Completed
• Phase: Phase 3
• Start date: July 11, 2019
• Est. completion date: June 30, 2023

Study information

• Verified date: November 2023
• Source: Innovent Biologics (Suzhou) Co. Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The anti-tumor activity of anti-PD-1 therapy and VEGF inhibitor in TKI-resistant EGFR-mutated non-squamous NSCLC Chinese patients will be investigated in this clinical trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 492
• Est. completion date: June 30, 2023
• Est. primary completion date: July 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Main Inclusion Criteria:

1. Signed written informed consent before any trial-related processes;

2. Age = 18 years and <75 years male or females;

3. Has a histologically or cytologically confirmed stage IIIB/IIIC (American Joint Committee on Cancer [AJCC] 8th edition) NSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy, or metastatic / recurrent non-squamous NSCLC;

4. Patients with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment

5. EGFR-TKI resistance, confirmed by RECIST 1.1

6. The investigator confirms at least one measurable lesion according to RECIST 1.1. A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed; The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1;

Exclusion criteria:

1. Squamous cell > 10%. If small cell types are present, the subject is not eligible for inclusion.;

2. Has previously received systemic anti-tumor treatment other than EGFR-TKI for or advanced non-squamous NSCLC (including cytotoxic chemotherapy for radiotherapy, do not include other systemic treatment for other cured tumors);

3. Has previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or any other stimulatory or inhibitory agents of T cell receptors (eg CTLA-4, OX-40, CD137);

4. Has received EGFR-TKI treatment within 2 weeks;

5. Diagnosed of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs.

6. History of pneumonitis requiring steroid therapy or the presence of interstitial lung disease within 1 year prior to the first dose of study drugs;

7. Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis.

Hemoptysis within 3 months,

8. Full-dose oral or parenteral anticoagulant or thrombolytic agent for 10 consecutive days within 2 weeks. prophylactic use of anticoagulants is allowed;

Related Conditions & MeSH terms

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

Intervention

Drug:
• Sintilimab
200mg IV Q3W
• IBI305
15mg/kg IV Q3W
• Pemetrexed
500mg/m2 IV Q3W
• Cisplatin
75mg/m2 IV Q3W
• Placebo1
Placebo1 IV Q3W
• Placebo2
Placebo2 IV Q3W

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Innovent Biologics (Suzhou) Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS (Progression Free Survival)		Time from randomization to first documented disease progression (radiographic) assessed by Independent Imaging Assessment Committee (IRRC) or death due to any cause. up to 24month
Secondary	OS (Overall Survival)		Time from randomization to the death of the subject due to any cause assessed up to 36 months.
Secondary	ORR (overall response rate)		The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months.
Secondary	PFS (Progression Free Survival)		Time from randomization to first documented disease progression (radiographic) assessed by investigator or death due to any cause up to 24 month.
Secondary	DCR(Disease control rate )		The proportion of subjects in the analysis population who had a complete response (CR) or partial response (PR) or stable disease (SD) up to 24 month.
Secondary	TTR(Time to objective response )		For subjects with CR or PR, defined as the time from randomization to the first documented CR or PR up to 24 month.
Secondary	DOR(Duration of response)		For subjects with CR or PR, defined as the time from the first documented CR or PR to disease progression or death up to 24 month.