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

• ClinicalTrials.gov Identifier: NCT03748134
• Recruitment Status: Recruiting
• First Posted: November 20, 2018
• Last Update Posted: February 2, 2021
• Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• 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: February 2, 2021
• Actual Study Start Date: December 13, 2018
• Estimated Primary Completion Date: July 14, 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: March 26, 2020)

• 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

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
• 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.
• 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: Placebo
  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

Study Arms

• 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: Placebo + chemotherapy

  Placebo in combination with investigator's choice of chemotherapy

  TP regimen: Cisplatin + paclitaxel

  or

  CP regimen: Cisplatin + fluorourcil

  Interventions:

  • Drug: Placebo
  • Drug: Cisplatin
  • Drug: Paclitaxel
  • Drug: Fluorouracil

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 26, 2020): 676
• Original Estimated Enrollment (submitted: November 18, 2018): 640
• Estimated Study Completion Date: July 30, 2022
• Estimated Primary Completion Date: July 14, 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 within 12 months to randomization.
• 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: Agnes Sun; +86 21 31820291; xiaolei.sun@innoventbio.com

Contact: Peter Pan; +86 21 31655781; xinchun.pan@innoventbio.com

• Listed Location Countries: Australia, Belgium, China, France, Spain, United States

Administrative Information

• NCT Number: NCT03748134
• Other Study ID Numbers: CIBI308A301
• 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

• Responsible Party: Innovent Biologics (Suzhou) Co. Ltd.
• Study Sponsor: Innovent Biologics (Suzhou) Co. Ltd.
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Innovent Biologics (Suzhou) Co. Ltd.
• Verification Date: January 2021