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

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)

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.

Study Overview

• Status: Completed
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: Sintilimab; Drug: IBI305; Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo2; Drug: Placebo1

• Study Type: Interventional
• Enrollment (Actual): 492
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: tengfei zou; Phone Number: +86 0512-69566088; Email: tengfei.zou@innoventbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sintilimab +IBI305+Pemetrexed+Cisplatin; Drug: Sintilimab 200mg IV Q3W Other Name: IBI308 Drug: IBI305 15mg/kg IV Q3W Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W	Drug: Sintilimab; 200mg IV Q3W; Other Names: IBI308; Drug: IBI305; 15mg/kg IV Q3W; Drug: Pemetrexed; 500mg/m2 IV Q3W; Drug: Cisplatin; 75mg/m2 IV Q3W
Experimental: Sintilimab +Placebo2+Pemetrexed+Cisplatin; Drug: Sintilimab 200mg IV Q3W Other Name: IBI308 Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W Drug: Placebo2 Placebo2 IV Q3W	Drug: Sintilimab; 200mg IV Q3W; Other Names: IBI308; Drug: Pemetrexed; 500mg/m2 IV Q3W; Drug: Cisplatin; 75mg/m2 IV Q3W; Drug: Placebo2; Placebo2 IV Q3W
Active Comparator: Placebo1+Placebo2+Pemetrexed+Cisplatin; Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W Drug: Placebo1 Placebo1 IV Q3W Drug: Placebo2 Placebo2 IV Q3W	Drug: Pemetrexed; 500mg/m2 IV Q3W; Drug: Cisplatin; 75mg/m2 IV Q3W; Drug: Placebo2; Placebo2 IV Q3W; Drug: Placebo1; Placebo1 IV Q3W

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
OS (Overall Survival)	Time from randomization to the death of the subject due to any cause assessed up to 36 months.
ORR (overall response rate)	The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months.
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.
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.
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.
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.

Collaborators and Investigators

• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.

Publications and helpful links

General Publications

• Lu S, Wu L, Jian H, Chen Y, Wang Q, Fang J, Wang Z, Hu Y, Sun M, Han L, Miao L, Ding C, Cui J, Li B, Pan Y, Li X, Ye F, Liu A, Wang K, Cang S, Zhou H, Sun X, Ferry D, Lin Y, Wang S, Zhang W, Zhang C. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022 Sep;23(9):1167-1179. doi: 10.1016/S1470-2045(22)00382-5. Epub 2022 Jul 28. Erratum In: Lancet Oncol. 2022 Sep;23(9):e404.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2019
• Primary Completion (Actual): July 31, 2021
• Study Completion (Actual): June 30, 2023

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 10, 2019
• First Posted (Actual): January 14, 2019

Study Record Updates

• Last Update Posted (Actual): November 27, 2023
• Last Update Submitted That Met QC Criteria: November 23, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Folic Acid Antagonists; Pemetrexed
• Other Study ID Numbers: CIBI338A301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No