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

NCT03802240 | Completed Phase 3

• 1 other identifier: CIBI338A301
• Study Type: interventional
• Target: 492
• Locations: 1 country
• Sites: 1

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.

Conditions

Non-Squamous Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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.

Study Arms (3)

Sintilimab +IBI305+Pemetrexed+Cisplatin

EXPERIMENTAL

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; Drug: IBI305; Drug: Pemetrexed; Drug: Cisplatin

Sintilimab +Placebo2+Pemetrexed+Cisplatin

EXPERIMENTAL

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; Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo2

Placebo1+Placebo2+Pemetrexed+Cisplatin

ACTIVE COMPARATOR

Drug: Pemetrexed 500mg/m2 IV Q3W Drug: Cisplatin 75mg/m2 IV Q3W Drug: Placebo1 Placebo1 IV Q3W Drug: Placebo2 Placebo2 IV Q3W

Drug: Pemetrexed; Drug: Cisplatin; Drug: Placebo1; Drug: Placebo2

Interventions

Sintilimab DRUG

200mg IV Q3W

Also known as: IBI308

Sintilimab +IBI305+Pemetrexed+Cisplatin; Sintilimab +Placebo2+Pemetrexed+Cisplatin

IBI305 DRUG

15mg/kg IV Q3W

Sintilimab +IBI305+Pemetrexed+Cisplatin

Pemetrexed DRUG

500mg/m2 IV Q3W

Placebo1+Placebo2+Pemetrexed+Cisplatin; Sintilimab +IBI305+Pemetrexed+Cisplatin; Sintilimab +Placebo2+Pemetrexed+Cisplatin

Cisplatin DRUG

75mg/m2 IV Q3W

Placebo1+Placebo2+Pemetrexed+Cisplatin; Sintilimab +IBI305+Pemetrexed+Cisplatin; Sintilimab +Placebo2+Pemetrexed+Cisplatin

Placebo1 DRUG

Placebo1 IV Q3W

Placebo1+Placebo2+Pemetrexed+Cisplatin

Placebo2 DRUG

Placebo2 IV Q3W

Placebo1+Placebo2+Pemetrexed+Cisplatin; Sintilimab +Placebo2+Pemetrexed+Cisplatin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent before any trial-related processes;
• Age ≥ 18 years and \<75 years male or females;
• 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;
• Patients with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment
• EGFR-TKI resistance, confirmed by RECIST 1.1
• 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;

You may not qualify if:

• 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);
• 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);
• Has received EGFR-TKI treatment within 2 weeks;
• 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.
• History of pneumonitis requiring steroid therapy or the presence of interstitial lung disease within 1 year prior to the first dose of study drugs;
• Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis.
• Hemoptysis within 3 months,
• Full-dose oral or parenteral anticoagulant or thrombolytic agent for 10 consecutive days within 2 weeks. prophylactic use of anticoagulants is allowed;

Sponsors & Collaborators

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

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

Location

Related Publications (2)

• Lu S, Wu L, Jian H, Cheng Y, Wang Q, Fang J, Wang Z, Hu Y, Han L, Sun M, Miao L, Ding C, Cui J, Wang K, Li B, Li X, Ye F, Liu A, Pan Y, Cang S, Zhou H, Sun X, Shen Y, Wang S, Zhang W, He Y. Sintilimab plus chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer with disease progression after EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): second interim analysis from a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2023 Jul;11(7):624-636. doi: 10.1016/S2213-2600(23)00135-2. Epub 2023 May 5.

  PMID: 37156249 DERIVED

• 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.

  PMID: 35908558 DERIVED

MeSH Terms

Interventions

sintilimab; Pemetrexed; Cisplatin

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2019
• First Posted: January 14, 2019
• Study Start: July 11, 2019
• Primary Completion: July 31, 2021
• Study Completion: June 30, 2023
• Last Updated: November 27, 2023

Record last verified: 2023-11

Locations

CN (1)