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

Innovent Biologics

Status and phase: Completed; Phase 3

Conditions: Esophageal Squamous Cell Carcinoma

Treatments: Biological: Sintilimab; Drug: Cisplatin; Drug: Placebo; Drug: Paclitaxel; Drug: Fluorouracil

Study type: Interventional

Funder types: Industry

Identifiers

NCT03748134

2020-000533-40 (Registry Identifier)

CIBI308A301

Details and patient eligibility

About

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

Enrollment: 746 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

746 participants in 3 patient groups

Randomized Part: Experimental: Sintilimab + chemotherapy

Experimental group

Description:

Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil

Treatment:

Biological: Sintilimab

Drug: Cisplatin

Drug: Paclitaxel

Drug: Fluorouracil

Randomised Part: Active Comparator: Placebo + chemotherapy

Active Comparator group

Description:

Placebo in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil

Treatment:

Drug: Placebo

Drug: Cisplatin

Drug: Paclitaxel

Drug: Fluorouracil

Open-label part: Sintilimab+ chemotherapy

Experimental group

Description:

Sintilimab in combination with investigator's choice of chemotherapy TP regimen: Cisplatin + paclitaxel or CP regimen: Cisplatin + fluorourcil

Treatment:

Biological: Sintilimab

Drug: Cisplatin

Drug: Paclitaxel

Drug: Fluorouracil