Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )

• ClinicalTrials.gov Identifier: NCT03748134
• Recruitment Status: Completed
• First Posted: November 20, 2018
• Last Update Posted: October 24, 2023
• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Collaborator: Fortrea
• Information provided by (Responsible Party): Innovent Biologics (Suzhou) Co. Ltd.

Tracking Information

• First Submitted Date: November 12, 2018
• First Posted Date: November 20, 2018
• Last Update Posted Date: October 24, 2023
• Actual Study Start Date: December 24, 2018
• Actual Primary Completion Date: September 9, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 26, 2020)

• OS in overall population [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
  To compare the overall survival of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with unresectable, locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ESCC)
• OS in PD-L1 positive population [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
  To compare the OS of sintilimab vs. placebo, in combination with chemotherapy, for first-line treatment in subjects with PD-L1 positive, unresectable, locally advanced, recurrent or metastatic ESCC

Original Primary Outcome Measures (submitted: November 18, 2018)

• OS [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
  Overall Survival
• OS in PD-L1 positive population [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 40 months. ]
  Overall Survival in PD-L1 positive population

Current Secondary Outcome Measures (submitted: July 26, 2021)

• ORR in overall population [ Time Frame: From date of randomization up to 28 months. ]
  To compare the objective response rate between the two treatment arms in ITT population
• PFS in overall populationsubjects in ITT population [ Time Frame: From date of randomization up to 28 months ]
  To compare the progression-free survival between the two treatment arms in ITT population
• DCR in overall population [ Time Frame: From date of randomization up to 28 months ]
  To compare the disease control rate between the two treatment arms in ITT population
• DoR in overall population [ Time Frame: From date of randomization up to 28 months ]
  To compare the duration of response between the two treatment arms in ITT population
• ORR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
  To compare the objective response rate between the two treatment arms in PD-L1 positive subjects in ITT population
• DCR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
  To compare the disease control rate between the two treatment arms in PD-L1 positive subjects in ITT population
• DoR - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
  To compare the duration of response between the two treatment arms in PD-L1 positive subjects in ITT population
• PFS - PD-L1 positive [ Time Frame: From date of randomization up to 28 months ]
  To compare the progression-free survival between the two treatment arms in PD-L1 positive subjects in ITT population

Original Secondary Outcome Measures (submitted: November 18, 2018)

PFS [ 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 28 months. ]

Progression Free Survival

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

Descriptive Information

• Brief Title: Sintilimab or Placebo With Chemotherapy in Esophageal Squamous Cell Carcinoma ( ORIENT-15 )
• Official Title: A Multicenter, Double-Blind, Randomized Phase 3 Clinical Trial Evaluating the Efficacy and Safety of Sintilimab vs. Placebo, in Combination With Chemotherapy, for First-Line Treatment of Unresectable, Locally Advanced, Recurrent, or Metastatic Esophageal Squamous Cell Carcinoma (ORIENT-15)

Brief Summary

This is a randomized, double-blind multi-center, phase III study comparing the efficacy and safety of sintilimab or placebo in combination with chemotherapy as first-line treatment in subjects with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma.

After the interim analysis conducted by the iDMC, an open-label assignment of experimental arm therapy will continue in regions outside of China, in order to further evaluate the efficacy and safety of sintilimab in combination with chemotherapy in subjects representing the western population with advanced esophageal squamous cell carcinoma

• 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: Esophageal Squamous Cell Carcinoma

Intervention

• Biological: Sintilimab
  For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1
• Drug: Cisplatin
  75mg/m^2 IV Q3W day 1
• Drug: Paclitaxel
  87.5 mg/m^2 IV Q3W day 1, day 8 for first cycle and 175mg/m^2 IV Q3W day 1 after first cycle
• Drug: Fluorouracil
  800 mg/m^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W
• Drug: Placebo
  For weight <60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1

Study Arms

• Experimental: Randomized Part: Experimental: Sintilimab + chemotherapy

  Sintilimab in combination with investigator's choice of chemotherapy

  TP regimen: Cisplatin + paclitaxel

  or

  CP regimen: Cisplatin + fluorourcil

  Interventions:

  • Biological: Sintilimab
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Fluorouracil
• Active Comparator: Randomised Part: Active Comparator: Placebo + chemotherapy
  Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
  Interventions:

  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Fluorouracil
  • Drug: Placebo
• Experimental: Open-label part: Sintilimab+ chemotherapy
  Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil
  Interventions:

  • Biological: Sintilimab
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Fluorouracil

• Publications *: Lu Z, Wang J, Shu Y, Liu L, Kong L, Yang L, Wang B, Sun G, Ji Y, Cao G, Liu H, Cui T, Li N, Qiu W, Li G, Hou X, Luo H, Xue L, Zhang Y, Yue W, Liu Z, Wang X, Gao S, Pan Y, Galais MP, Zaanan A, Ma Z, Li H, Wang Y, Shen L; ORIENT-15 study group. Sintilimab versus placebo in combination with chemotherapy as first line treatment for locally advanced or metastatic oesophageal squamous cell carcinoma (ORIENT-15): multicentre, randomised, double blind, phase 3 trial. BMJ. 2022 Apr 19;377:e068714. doi: 10.1136/bmj-2021-068714.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 10, 2021): 746
• Original Estimated Enrollment (submitted: November 18, 2018): 640
• Actual Study Completion Date: July 29, 2023
• Actual Primary Completion Date: September 9, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Histopathologically confirmed unresectable, locally advanced, recurrent or metastatic ESCC (excluding mixed adenosquamous carcinoma and other histological subtypes)
• ECOG PS of 0 or 1
• Subject must be unsuitable for definitive treatment, such as definitive chemoradiotherapy and/or surgery. For subjects who have received (neo)adjuvant or definitive chemotherapy/radiochemotherapy, time from the completion of last treatment to disease recurrence must be > 6 months Could provide archival or fresh tissues for PD-L1 expression analysis with obtainable results
• Have at least one measurable lesion as per RECIST v1.1

Key exclusion Criteria:

• ESCC with endoscopy-confirmed near-complete obstruction requiring interventional therapy
• Post stent implantation in the esophagus or trachea with risk of perforation
• Received systemic treatment for advanced or metastatic ESCC.
• Received a cumulative dose of cisplatin ≥ 300 mg/m2 and the last cisplatin dose was within 12 months of randomization or the first dose of study treatment in the open-label phase.
• High risk of hemorrhage or perforations due to tumor invasion in adjacent organs (aorta or trachea), or have fistula formation.
• Hepatic metastasis > 50% of the total liver volume.
• Received palliative therapy for a local lesion within 2 weeks prior to the first dose.
• Received systemic treatment with Chinese traditional medicines with anti-cancer indications or immunomodulators (including thymosins, interferons, and interleukins) within 2 weeks prior to the first dose of study treatment.
• Received systemic immunosuppressants within 2 weeks prior to randomization, excluding local use of glucocorticoids administered by nasal, inhaled, or other routes, and systemic glucocorticoids at physiological doses (no more than 10 mg/day of prednisone or equivalents), or glucocorticoids to prevent allergies to contrast media.

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: Australia, Belgium, China, France, Hungary, Spain, United States

Administrative Information

• NCT Number: NCT03748134
• Other Study ID Numbers: CIBI308A301; 2020-000533-40 ( Registry Identifier: EudraCT )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• 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: Fortrea
• Investigators: Not Provided
• PRS Account: Innovent Biologics (Suzhou) Co. Ltd.
• Verification Date: October 2023