Phase II Study Evaluating Safety and Efficacy of Tislelizumab for Elderly Patients Unfit for Chemotherapy, With Advanced Esophageal Squamous-cell Carcinoma (SAFE ESO)

PRODIGE 102 - FFCD 2201 - SAFE-ESO Phase II Study Evaluating Safety and Efficacy of Tislelizumab for Elderly Patients Unfit for Chemotherapy, With Advanced Esophageal Squamous-cell Carcinoma

The goal of this clinical trial is to assess the percentage of patients alive at 6 months in elderly patients, not eligible to an platinum-based chemotherapy, but who can received the Tislelizumab treatment alone as first-line treatment for an advanced esophageal squamous-cell carcinoma (ESCC).

Tislelizumab is a monoclonal antibody administred by intravenous infusion

This study aims to anwer too at the questions:

• the Safety of the drug
• Overall survival (OS) at 6 months according the diagnostic of PD-L1 expression (PD-L1 is a protein present on the surface of immune cells)
• Overall response rate (ORR) according to imagery criteria
• Progression-free survival (PFS) at 3 and 6 months according to imagery criteria and depending on PDL1 expression
• Patients' health-related quality of life
• OS and PFS according to geriatric parameters
• Prognostic value of immune biomarkers

Study Overview

• Status: Recruiting
• Conditions: Esophageal Squamous Cell Carcinoma (ESCC)
• Intervention / Treatment: Drug: Tislelizumab is a fully humanized monoclonal antibody specific for human PD-1

Detailed Description

This is a multicenter open-label single arm phase II study to evaluate Tislelizumab in monotherapy in frontline metastatic or locally advanced ESCC.

Patient aged ≥70 years will be selected for inclusion after a diagnosis of metastatic or locally advanced ESCC, and if they are not eligible for a platinum-based chemotherapy regimen.

Tislelizumab (200 mg flat dose every 3 weeks) will be received by intravenous perfusion until progression or unacceptable toxicity, for a maximum of 2 years.

The patients will be included regardless of PD-L1 status; A comparison for all study population will be carried out centrally as part of the ancillary enquiries.

• Study Type: Interventional
• Enrollment (Estimated): 95
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lise Laclautre; Phone Number: 0473754963; Email: promo_interne_drci@chu-clermontferrand.fr

Study Locations

• France
  • Amiens, France
    • Not yet recruiting
    • CHU Amiens
    • Principal Investigator: Vincent HAUTEFEUILLE
  • Avignon, France
    • Not yet recruiting
    • Institut régional du cancer Provence d'Avignon
    • Principal Investigator: May MABRO
  • Bayonne, France, 64100
    • Not yet recruiting
    • Centre Hospitalier de la Cote Basque
    • Principal Investigator: Franck Audemar
  • Besançon, France
    • Recruiting
    • CHU Besancon
    • Principal Investigator: Angélique VIENOT
  • Beuvry, France
    • Recruiting
    • ICHF Centre Pierre Curie
    • Principal Investigator: BASSON Laurent
  • Beuvry, France
    • Recruiting
    • CH Béthune et Beuvry
    • Principal Investigator: Hélène VAN DAMME
  • Brest, France
    • Recruiting
    • CHRU BREST
    • Principal Investigator: Jean-Philippes METGES
  • Caen, France
    • Recruiting
    • Centre Francois Baclesse
    • Principal Investigator: Aurélie PARZY
  • Clermont-Ferrand, France
    • Not yet recruiting
    • Chu Clermont-Ferrand
    • Contact: Lise Laclautre
    • Contact: Lise Laclautre; Phone Number: 0473754963; Email: promo_interne_drci@chu-clermontferrand.fr
    • Principal Investigator: Marine JARY
  • Dijon, France
    • Not yet recruiting
    • CHU Dijon
    • Principal Investigator: Sylvain MANFREDI
  • Grenoble, France
    • Not yet recruiting
    • Groupe Hospitalier Mutualiste
    • Principal Investigator: Hélène FLESCH
  • Lille, France
    • Recruiting
    • CHRU LILLE
    • Principal Investigator: Anthony TURPIN
  • Limoges, France
    • Not yet recruiting
    • CHU Limoges
    • Principal Investigator: Frédéric THUILLIER
  • Lyon, France
    • Not yet recruiting
    • Centre Léon BERARD de Lyon
    • Principal Investigator: Clélia COUTZAC
  • Nancy, France
    • Recruiting
    • CHU Nancy
    • Principal Investigator: Marie MULLER
  • Paris, France
    • Recruiting
    • Hopital Europeen Georges-Pompidou
    • Principal Investigator: Aziz ZANAAN
  • Paris, France
    • Recruiting
    • Hôpital Saint-Louis Lariboisière
    • Principal Investigator: Thomas APARICIO
  • Paris, France
    • Recruiting
    • Le Groupe Hospitalier Diaconesses Croix Saint-Simon de Paris
    • Principal Investigator: Olivier DUBREUIL
  • Perpignan, France
    • Not yet recruiting
    • Centre Hospitalier de Perpignan
    • Principal Investigator: Faiza KHEMISSA AKOUZ
  • Poitiers, France
    • Recruiting
    • CHU Poitiers
    • Principal Investigator: David TOUGERON
  • Reims, France
    • Not yet recruiting
    • CHU de Reims
    • Principal Investigator: Olivier BOUCHE
  • Reims, France, 51726
    • Not yet recruiting
    • Centre Régional du Lutte Contre Le Cancer - Institut Godinot
    • Principal Investigator: Damien BOTSEN
  • Rennes, France
    • Recruiting
    • CHU Rennes
    • Principal Investigator: Astrid LIEVRE
  • Rouen, France
    • Recruiting
    • CHU Rouen
    • Principal Investigator: Frédéric DI FIORE
  • Saint-Herblain, France
    • Recruiting
    • Institut de Cancérologie de l'Ouest
    • Principal Investigator: Judith RAIMBOURG
  • St-Malo, France
    • Recruiting
    • Groupe Hospitalier Rance Emeraude
    • Principal Investigator: Anaïs BODERE
  • Strasbourg, France
    • Not yet recruiting
    • Institut Public de Cancérologie Strauss Europe,
    • Principal Investigator: Meher BEN ABDELGHANI
  • Tours, France
    • Not yet recruiting
    • CHRU Tours
    • Principal Investigator: Thierry LECOMTE
  • Villeurbanne, France
    • Recruiting
    • Medipole Hopital Mutualiste
    • Principal Investigator: Matthieu SARABI
  • Epagny Metz-Tessy
    • Annecy, Epagny Metz-Tessy, France, 74370
      • Not yet recruiting
      • Centre Hospitalier Annecy Genevois
      • Principal Investigator: Aude Montchaud

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically proven esophageal squamous cell carcinoma (ESCC)
• Metastatic or locally advanced cancer
• Absence of previous treatment (immunotherapy, chemotherapy or radiotherapy) in first line setting
• Ineligibility for a platinum-based chemotherapy assessed by oncologist and geriatrician
• At least one evaluable and/or measurable lesion as defined by RECIST v1.1 criteria
• Patients ≥ 70 years
• Subjects with WHO performance status ≤ 2
• Estimated life expectancy >3 months
• Adjuvant therapy finished >6 months

• Adequate marrow and organ functions defined as:

  • Absolute neutrophil count (ANC) ≥ 1 × 109/L,
  • Platelet count ≥ 75 × 109/L,
  • Hemoglobin ≥ 90 g/L,
  • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 × ULN, or AST and ALT ≤5 ×ULN for patients with liver metastases
  • ALP ≤ 5 x ULN unless liver metastases are present, in which case it must be ≤ 10x ULN
  • Measured creatinine clearance (CL) > 40 mL/min (MDRD method)
• Male patients must use a condom during treatment and for 6 months after the last dose when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential during treatment and for 6 months after the last dose.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations including follow up.
• Signed written informed consent obtained prior to any study specific procedures
• Patient affiliated to a social security scheme

Exclusion Criteria:

• History of another primary malignancy. May be included, patients with:

  • Malignancy treated with curative intent and with no known active disease ≥ 2 years before the first dose of treatment
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
  • Adequately treated carcinoma in situ without evidence of disease
• Locally advanced esophageal carcinoma that is resectable or potentially curable with radiation therapy per local investigator
• Participation in another clinical study with an investigational product during the last 2 months.
• Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• History of allogenic organ, bone marrow, or double umbilical cord blood transplantation

• Active documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). May be included:

  • Patients with vitiligo or alopecia
  • Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients with celiac disease controlled by diet alone
• Previous immune checkpoint inhibitor therapy within the 2 years before inclusion

• Uncontrolled intercurrent illness; uncontrollable pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention (recurrence ≤ 14 days after intervention). Patients with the following diseases are not excluded and may proceed to further screening:

  • Controlled Type I diabetes
  • Hypothyroidism (provided it is managed with hormone replacement therapy only)
  • Controlled celiac disease
  • Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
  • Any other disease that is not expected to recur in the absence of external triggering factors
• Patients with evidence of fistula (either oesophageal/bronchial or oesophageal/aorta)
• Patients considered at poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease, or active, uncontrolled ventricular arrhythmia, recent (within 6 months) myocardial infarction, pulmonary embolism/deep vein thrombosis, cerebrovascular accident, and heart failure, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, interstitial bilateral lung disease on high Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug abuse or dependence that will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or AEs or might impair compliance with study conduct. A history of severe hypersensitivity reactions to other monoclonal antibodies. Has received any chemotherapy, immunotherapy (eg, interleukin, interferon, thymosin, etc) or any investigational therapies within 14 days or 5 half-lives (whichever is shorter) of the first study drug administration.
• Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of MDS/AML.
• Patient with symptomatic central nervous system (CNS) metastases.
• History of active primary immunodeficiency.
• Known non-controlled serologically positive human immunodeficiency virus (HIV) patients with CD4 < 400 / mm3.
• Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), active untreated hepatitis B (known positive HBV surface antigen (HBsAg) result), active untreated hepatitis C. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.

• Current or prior use of immunosuppressive medication within 14 days before the first dose of -immunotherapy. The following are exceptions to this criterion:

  • Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)
• Receipt of live attenuated vaccine within 30 days prior to the first dose of ICI
• Follow-up impossible, according to investigator's decision
• Any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol or follow-up schedule
• Persons i) deprived of liberty by judicial or administrative decision, persons subject to psychiatric care under Articles L. 3212-1 and L. 3213-1 who do not fall under the provisions of Article L. 1121-8 and persons admitted to a health or social care facility for purposes other than research, and (ii) adults subject to a legal protection measure or unable to express their consent (Article L1121-8)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: all patients receive the Tislelizumab on monotherapy	Drug: Tislelizumab is a fully humanized monoclonal antibody specific for human PD-1; It is the first study which evaluate efficacy and safety of anti PD-1 immune checkpoint inhibitor alone in the first-line treatment of elderly esophageal squamous-cell carcinoma patients who no fit to received chemotherapy with platine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the percentage of patients alive at 6 months in elderly patients, not eligible to platinum-based chemotherapy, treated by anti-PD1 Tislelizumab alone as first-line treatment for an advanced ESCC	to assess the rate of evaluable patients (i.e., those not lost to follow-up at 6 months and who have received at least one dose of the study treatment) who are alive at 6 months after inclusion to patient rate measurement	6 month after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety according to NCI-CTCAE version 5.0	all grade and severe (grade 3-5) toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, will be recorded until 90 days after the last administration of treatment	time between the date of the first dose treatment with tislelizumab and the date within the 90 days after the last dose of treatment
- Overall survival (OS) at 6 months depending on PD-L1 expression	Overall survival (OS) will be estimated by the time between the date of the first dose treatment with tislelizumab and the date of death (whatever the cause) or date of last news for alive patients	time between the date of the first dose treatment with tislelizumab and the date of death (whatever the cause) or date of last news for alive patients
- Overall response rate (ORR) according to RECIST 1.1 criteria	The Overall Response Rate (ORR): is defined as the proportion of patients who achieved complete response (CR) or partial response (PR) as the best response during the treatment. evaluated by the investigator according to RECIST 1.1 criteria.	the time between the date of the first dose treatment with tislelizumab and the date of last dose of treatment
Progression-free survival (PFS) at 3 and 6 months according to RECIST 1.1 criteria and depending on PDL1 expression	Progression free survival (PFS) is defined by the time between the date of the first dose treatment with tislelizumab and the date of first progression (clinical and/or radiological; RECIST 1.1 criteria) determined by the investigator, or date of death (whatever the cause), whichever occurs first. Patients alive without progression will be censored at the date of last news.	at 3 month and 6 month after inclusion
Patients' health according the questionnary quality of life C30 of EORTC	Quality of life will be assessed with the questionnary quality of life C30 of EORTC (version 3.0) at each evaluation. Each questionnaire will be scored according to the relevant scoring manual. If half or more of the elements, which calculate a scale, are missing then the scale will be set to missing as per the scoring manuals. A scale cannot be estimated for the single item scales if the question they relate to has not been answered	time between the date of the first dose treatment with tislelizumab and the date within the 30 days after the last dose of treatment
Patients' health according the questionnary quality of life OES-18 of EORTC	Quality of life will be assessed with the questionnary quality of life OES-18 of EORTC at each evaluation. Each questionnaire will be scored according to the relevant scoring manual. If half or more of the elements, which calculate a scale, are missing then the scale will be set to missing as per the scoring manuals. A scale cannot be estimated for the single item scales if the question they relate to has not been answered	time between the date of the first dose treatment with tislelizumab and the date within the 30 days after the last dose of treatment
Patients' health according the questionnary quality of life ELD14 of EORTC	Quality of life will be assessed with the questionnary quality of life ELD14 of EORTC at each evaluation. Each questionnaire will be scored according to the relevant scoring manual. If half or more of the elements, which calculate a scale, are missing then the scale will be set to missing as per the scoring manuals. A scale cannot be estimated for the single item scales if the question they relate to has not been answered	time between the date of the first dose treatment with tislelizumab and the date within the 30 days after the last dose of treatment
Geriatric assessment according the questionnary G-CODE	Geriatric assessment will be performed at baseline and during treatment using the complete G-CODE which assesses the patient's autonomy in their daily life	time between the date of the first dose treatment with tislelizumab and the date within the 30 days after the last dose of treatment
Prognostic value of immune biomarkers	All patients, participating in the clinical study, will have blood drawn for the biological assessments at baseline and at the first radiological tumoral evaluation.	the time between the date of the first dose treatment with tislelizumab and the first radiological tumoral evaluation at 9 weeks after C1J1

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Federation Francophone de Cancerologie Digestive; BeiGene USA, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030

Study Registration Dates

• First Submitted: September 12, 2025
• First Submitted That Met QC Criteria: September 25, 2025
• First Posted (Actual): October 3, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: chemotherapy; immunotherapy; oncology; Ederly patients; digestive oncology; microenvironment biomarker; oncogeriatric domain
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Neoplasms
• Other Study ID Numbers: PHRC K 2023 JARY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No