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.

Tracking Information

• First Submitted Date: January 7, 2019
• First Posted Date: January 14, 2019
• Last Update Posted Date: November 27, 2023
• Actual Study Start Date: July 11, 2019
• Actual Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 18, 2022): 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 ]
• Original Primary Outcome Measures (submitted: January 10, 2019): PFS (Progression Free Survival) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8.7 month. ]

Current Secondary Outcome Measures (submitted: January 18, 2022)

• OS (Overall Survival) [ Time Frame: Time from randomization to the death of the subject due to any cause assessed up to 36 months. ]
• 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. ]
• 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. ]
• 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. ]
• 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. ]
• 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. ]

Original Secondary Outcome Measures (submitted: January 10, 2019)

• OS (Overall Survival) [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 11.3 month. ]
• ORR (overall response rate) [ Time Frame: Percentage of patients whose disease decreased (Partial response - PR) and/or disappears (Complete response - CR) after randomization. assessed up to 24 month. ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sintilimab ± IBI305 Plus Chemotherapy (Pemetrexed + Cisplatin) for EGFRm + Locally Advanced or Metastasis Non-Squamous NSCLC Patients After EGFR-TKI Treatment Failure
• 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• 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: Placebo1
  Placebo1 IV Q3W
• Drug: Placebo2
  Placebo2 IV Q3W

Study Arms

• 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

  Interventions:

  • Drug: Sintilimab
  • Drug: IBI305
  • Drug: Pemetrexed
  • Drug: Cisplatin
• 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

  Interventions:

  • Drug: Sintilimab
  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Placebo2
• 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

  Interventions:

  • Drug: Pemetrexed
  • Drug: Cisplatin
  • Drug: Placebo1
  • Drug: Placebo2

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 23, 2023): 492
• Original Estimated Enrollment (submitted: January 10, 2019): 480
• Actual Study Completion Date: June 30, 2023
• Actual Primary Completion Date: July 31, 2021 (Final data collection date for primary outcome measure)

Eligibility 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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT03802240
• Other Study ID Numbers: CIBI338A301
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Innovent Biologics (Suzhou) Co. Ltd.
• Verification Date: November 2023