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

NCT03748134 | Completed Phase 3 DMC FDA Drug

• 2 other identifiers: CIBI308A3012020-000533-40
• Study Type: interventional
• Target: 746
• Locations: 7 countries
• Sites: 48

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

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

ESCC; Esophageal Cancer; Esophageal Neoplasms; Esophageal Neoplasms Malignant; Esophageal Squamous Cell Carcinoma; Neoplasms, Squamous Cell; Esophageal Diseases; Carcinoma, Squamous Cell; Gastrointestinal Diseases; Paclitaxel; Cisplatin; Fluorouracil; Antineoplastic Agents; Anti-PD-1; Sintilimab

Outcome Measures

Primary Outcomes (2)

• OS in overall population

  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)

  From date of randomization until the date of death from any cause, assessed up to 40 months.

• OS in PD-L1 positive population

  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

  From date of randomization until the date of death from any cause, assessed up to 40 months.

Secondary Outcomes (8)

• ORR in overall population

  From date of randomization up to 28 months.

• PFS in overall populationsubjects in ITT population

  From date of randomization up to 28 months

• DCR in overall population

  From date of randomization up to 28 months

• DoR in overall population

  From date of randomization up to 28 months

• ORR - PD-L1 positive

  From date of randomization up to 28 months

Study Arms (3)

Randomized Part: Experimental: Sintilimab + chemotherapy

EXPERIMENTAL

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

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

Randomised Part: Active Comparator: Placebo + chemotherapy

ACTIVE COMPARATOR

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

Drug: Cisplatin; Drug: Paclitaxel; Drug: Fluorouracil; Drug: Placebo

Open-label part: Sintilimab+ chemotherapy

EXPERIMENTAL

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

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

Interventions

Sintilimab BIOLOGICAL

For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1

Open-label part: Sintilimab+ chemotherapy; Randomized Part: Experimental: Sintilimab + chemotherapy

Cisplatin DRUG

75mg/m\^2 IV Q3W day 1

Open-label part: Sintilimab+ chemotherapy; Randomised Part: Active Comparator: Placebo + chemotherapy; Randomized Part: Experimental: Sintilimab + chemotherapy

Paclitaxel DRUG

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

Open-label part: Sintilimab+ chemotherapy; Randomised Part: Active Comparator: Placebo + chemotherapy; Randomized Part: Experimental: Sintilimab + chemotherapy

Fluorouracil DRUG

800 mg/m\^2 IV continuous infusion over 24 hours daily on Days 1-5 Q3W

Open-label part: Sintilimab+ chemotherapy; Randomised Part: Active Comparator: Placebo + chemotherapy; Randomized Part: Experimental: Sintilimab + chemotherapy

Placebo DRUG

For weight \<60kg, 3mg/kg IV Q3W day 1, and for weight≥60kg, 200mg IV Q3W day 1

Randomised Part: Active Comparator: Placebo + chemotherapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (48)

St. Joseph Heritage Healthcare - Virginia K. Crosson Cancer Center

Anaheim, California, 92835, United States

Location

UC Irvine

Orange, California, 92868, United States

Location

Rocky Mountain Cancer Centers, LLP

Denver, Colorado, 80218, United States

Location

IACT Health - John B. Amos Cancer center

Columbus, Georgia, 31904, United States

Location

Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Texas Oncology, P.A.

Austin, Texas, 78705, United States

Location

Northwest Cancer Specialists, P.C.

Vancouver, Washington, 98684, United States

Location

Border Medical Oncology

East Albury, New South Wales, 2640, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Austin Hospital

Heidelberg, Victoria, 3079, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

St John of God Subiaco Hospital

Subiaco, Western Australia, 6008, Australia

Location

University Hospital Gent

Ghent, Corneel Heymanslaan 10, 9000, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, Herestraat 49, 3000, Belgium

Location

Cliniques Universitaires Saint-Luc Av.

Brussels, Hippocrate 10, 1200, Belgium

Location

Institut Jules Bordet

Brussels, 1000, Belgium

Location

Centre Hospitalier Regional de Verviers

Verviers, 4800, Belgium

Location

Beijing Cancer Hospital

Beijing, China

Location

Hôpital Jean Minjoz

Bettancourt-la-Ferrée, 25000, France

Location

Institut Bergonié

Bordeaux, 33000, France

Location

Centre François Baclesse

Caen, 14000, France

Location

CHU Estaing

Clermont-Ferrand, 63000, France

Location

CHU Estaing

Clermont-Ferrand, 63100, France

Location

Faculte de Medecine

Dijon, 21000, France

Location

Universite de Bourgogne - Faculte de Medecine - INSERM U866

Dijon, 21079, France

Location

Oscar Lambret Centre

Lille, 59020, France

Location

CHU Hôpital de la Timone

Marseille, 13005, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

CHU de Poitiers

Poitiers, 86021, France

Location

Hôpital Charles-Nicolle de Rouen

Rouen, 76000, France

Location

Institut de Cancérologie de Lorraine

Vandœuvre-lès-Nancy, 54500, France

Location

Országos Onkológiai Intézet

Budapest, Ráth György U. 7-9, 1122, Hungary

Location

Jósa András Oktatókórház

Nyíregyháza, Szent István U. 68, 4400, Hungary

Location

University Hospital Marqués de Valdecilla

Santander, Cantabria, 39008, Spain

Location

Hospital del Mar

Barcelona, 08001, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Universitario de Fuenlabrada

Fuenlabrada, 28942, Spain

Location

Hospital Universitari de Girona Doctor Josep Trueta

Girona, Spain

Location

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, 25198, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, 280402, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

Clínica Universidad de Navarra

Pamplona, 31008, Spain

Location

Parc Taulí Sabadell Hospital Universitari

Sabadell, 08208, Spain

Location

Complexo Hospitalario Universitario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41003, Spain

Location

Consorci Hospital General Universitari de València

Valencia, 46016, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

Related Publications (3)

• Lu Z, Kong L, Wang B, Wang J, Liu L, Shu Y, Yang L, Sun G, Cao G, Ji Y, Cui T, Liu H, Qiu W, Li N, Li G, Luo H, Hou X, Zhang Y, Yue W, Xue L, Liu Z, Pan Y, Gao S, Wang X, Pan Z, Zhang S, Lin G, Xie Y, Gu K, Ren T, Li W, Li T, Wang S, He W, Fan Y, Liang J, Xia B, Zhao L, Wang S, Shen L. Effects of sintilimab plus chemotherapy as first-line treatment on health-related quality of life in patients with advanced esophageal squamous cell carcinoma: results from the randomized phase 3 ORIENT-15 study. EClinicalMedicine. 2024 May 17;72:102623. doi: 10.1016/j.eclinm.2024.102623. eCollection 2024 Jun.

  PMID: 38800802 DERIVED

• Zhang Y, Li C, Du K, Pengkhun N, Huang Z, Gong M, Li Y, Liu X, Li L, Wang D, Wang C, Chen F, Li J. Comparative analysis of immune checkpoint inhibitors in first-line treatment of esophageal squamous cell carcinoma: a network meta-analysis. Immunotherapy. 2023 Jul;15(10):737-750. doi: 10.2217/imt-2022-0236. Epub 2023 May 4.

  PMID: 37139963 DERIVED

• 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.

  PMID: 35440464 DERIVED

MeSH Terms

Conditions

Esophageal Squamous Cell Carcinoma; Esophageal Neoplasms; Neoplasms, Squamous Cell; Esophageal Diseases; Carcinoma, Squamous Cell; Gastrointestinal Diseases

Interventions

sintilimab; Cisplatin; Paclitaxel; Fluorouracil

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic 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: November 12, 2018
• First Posted: November 20, 2018
• Study Start: December 24, 2018
• Primary Completion: September 9, 2021
• Study Completion: July 29, 2023
• Last Updated: October 24, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

ES (15); FR (13); US (7); HU (2); AU (5); BE (5); CN (1)