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

• ClinicalTrials.gov Identifier: NCT03802240
• Recruitment Status: Completed
• First Posted: January 14, 2019
• Last Update Posted: November 27, 2023
• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Information provided by (Responsible Party): Innovent Biologics (Suzhou) Co. Ltd.

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Non-Squamous Non-Small Cell Lung Cancer	Drug: Sintilimab; Drug: IBI305; Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo1; Drug: Placebo2	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 492 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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)
• Actual Study Start Date: July 11, 2019
• Actual Primary Completion Date: July 31, 2021
• Actual Study Completion Date: June 30, 2023

Arms and Interventions

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 Name: 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 Name: 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: Placebo1; Placebo1 IV Q3W; Drug: Placebo2; Placebo2 IV Q3W

Outcome Measures

Primary Outcome Measures :

1. PFS (Progression Free Survival) [ Time Frame: 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 :

1. OS (Overall Survival) [ Time Frame: Time from randomization to the death of the subject due to any cause assessed up to 36 months. ]
2. ORR (overall response rate) [ Time Frame: The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months. ]
3. PFS (Progression Free Survival) [ Time Frame: Time from randomization to first documented disease progression (radiographic) assessed by investigator or death due to any cause up to 24 month. ]
4. DCR(Disease control rate ) [ Time Frame: 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. ]
5. TTR（Time to objective response ) [ Time Frame: For subjects with CR or PR, defined as the time from randomization to the first documented CR or PR up to 24 month. ]
6. DOR(Duration of response) [ Time Frame: 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. ]

Eligibility Criteria

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

Criteria

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;

Contacts and Locations

Locations

China, Shanghai

Shanghai Chest Hospital

Shanghai, Shanghai, China, 200030

Sponsors and Collaborators

Innovent Biologics (Suzhou) Co. Ltd.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• ClinicalTrials.gov Identifier: NCT03802240
• Other Study ID Numbers: CIBI338A301
• First Posted: January 14, 2019
• Last Update Posted: November 27, 2023
• Last Verified: November 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pemetrexed; Antineoplastic Agents; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Folic Acid Antagonists; Nucleic Acid Synthesis Inhibitors