Durvalumab in Patients With Treatment-Naive Stage IV NSCLC With an ECOG Performance Status of 2 to 3 and High PD-L1 Tumor Expression (IFCT-1802 SAVIMMUNE): A Multicenter Phase 2 Trial

Valérie Gounant; Laurent Greillier; Céline Mascaux; François Pinquie; Delphine Carmier; Lionel Moreau; Benoît Roch; Didier Debieuvre; Xavier Dhalluin; Etienne Giroux-Leprieur; Elodie Berton; Audrey Rabeau; Judith Raimbourg; Adrien Dixmier; Charles Naltet; Antoine Khalil; Lynn Ezzeddine; Mostafa El Hajjam; Alexandra Langlais; Franck Morin; Virginie Westeel; Gérard Zalcman; Michael Duruisseaux

doi:10.1016/j.jtocrr.2025.100908

Durvalumab in Patients With Treatment-Naive Stage IV NSCLC With an ECOG Performance Status of 2 to 3 and High PD-L1 Tumor Expression (IFCT-1802 SAVIMMUNE): A Multicenter Phase 2 Trial

JTO Clin Res Rep. 2025 Sep 18;6(12):100908. doi: 10.1016/j.jtocrr.2025.100908. eCollection 2025 Dec.

Authors

Valérie Gounant¹, Laurent Greillier², Céline Mascaux³, François Pinquie⁴, Delphine Carmier⁵, Lionel Moreau⁶, Benoît Roch⁷, Didier Debieuvre⁸, Xavier Dhalluin⁹, Etienne Giroux-Leprieur¹⁰, Elodie Berton¹¹, Audrey Rabeau¹², Judith Raimbourg¹³, Adrien Dixmier¹⁴, Charles Naltet¹⁵, Antoine Khalil¹⁶, Lynn Ezzeddine¹⁶, Mostafa El Hajjam¹⁷, Alexandra Langlais¹⁸, Franck Morin¹⁸, Virginie Westeel¹⁹, Gérard Zalcman¹, Michael Duruisseaux²⁰

Affiliations

¹ Université Paris Cité, Thoracic Oncology, CIC INSERM 1425, Bichat Claude Bernard Hospital, Paris, France.
² Multidisciplinary Oncology and Therapeutic Innovations, Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
³ Pulmonology, Hopitaux Universitaires de Strasbourg - Nouvel Hôpital Civil, Strasbourg, France.
⁴ Pulmonology, Centre Hospitalier du Mans, Le Mans, France.
⁵ Pulmonology, CHRU Hopitaux de Tours - Hôpital Bretonneau, Tours, France.
⁶ Pulmonology, Hôpitaux Civils de Colmar, Colmar, France.
⁷ Equipe Pneumologie et Oncologie, Service de Pneumologie, Allergologie et Oncologie Thoracique, CHU Montpellier - Université de Montpellier, Montpellier, France.
⁸ Pulmonology, E. Muller Hospital - GHRMSA, Mulhouse, France.
⁹ Pulmonology and Thoracic Oncology, Institut Cœur Poumon, Lille, France.
¹⁰ Université Paris-Saclay, UVSQ, APHP-Hôpital Ambroise Paré, Respiratory Diseases and Thoracic Oncology, Boulogne-Billancourt, France.
¹¹ Pulmonology, CHU de Grenoble, Grenoble, France.
¹² Pulmonology, CHU de Toulouse, Toulouse, France.
¹³ Medical Oncology, ICO Institut de Cancérologie de l'Ouest, Saint-Herblain, France.
¹⁴ Pulmonology and Thoracic Oncology, C.H.U. Orleans - La Source, Orleans, France.
¹⁵ Thoracic Oncology, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
¹⁶ Université Paris Cité, Medical Imaging, Bichat Claude Bernard Hospital, Paris, France.
¹⁷ Imagerie Interventionnelle, Hôpital Ambroise Paré, Boulogne-Billancourt, France.
¹⁸ Clinical Research Unit, French Cooperative Thoracic Intergroup (IFCT), Paris, France.
¹⁹ Pulmonology - Hôpital Jean Minjoz, Besançon, France.
²⁰ Pulmonology - Hôpital Louis Pradel, Hospices Civils de Lyon, Bron, France.

Abstract

Introduction: Eastern Cooperative Oncology Group performance status 2 to 3 is associated with poor survival and chemotherapy-related adverse events (AEs). The impact of poor PS on the safety and efficacy of immune checkpoint inhibitors has not been elucidated. This study aimed to assess first-line durvalumab in patients with PS 2 to 3 with advanced NSCLC and high programmed cell death-ligand 1 (PD-L1) expression.

Methods: In this single-arm, prospective, multicenter, phase II trial, patients with PS 2 to 3 aged 18 to 75 years with metastatic NSCLC and PD-L1 tumor proportion score more than or equal to 25% received durvalumab until progression or toxicity. Primary end point was safety, that is incidence of grade more than or equal to 3 TRAEs during the first 8 weeks. Secondary end points included blinded independent central review overall response rate, progression-free survival, duration of response, overall survival (OS), and PS improvement at 8 weeks and health-related quality of life.

Results: A total of 50 patients were enrolled. Median follow-up was 26.2 (19.9-35.2) months. Prevalence of grade more than or equal to 3 TRAEs during the first 8 weeks was 10.0% (five of 50, 95% confidence interval [CI] 1.7-18.3), and no grade 5 occurred. Overall response rate at 8 weeks was 26% (95% CI 13.8-38.2). Median duration of response, progression-free survival, and OS were 11.8 months (95% CI, 7.2-not reached), 2.3 months (95% CI 1.7-5.6), and 7.1 months (95% CI 3.9-14.5), respectively. The 12-month OS rate was 40% (95% CI 26.5-53.1). Median OS in patients with PS 2 and PS 3 was 11.4 (95% CI 4.4-32.8) and 3.0 (95% CI 0.2-5.6) months, respectively. Of 27 patients, 12 (44.4%) still receiving durvalumab at 8 weeks had improved PS (p = 0.0096). Mean global QLQ-C30 score significantly increased at 8 weeks.

Conclusions: In patients with a PS of 2 to 3 with advanced NSCLC and high PD-L1 expression, first-line durvalumab was safe with 40% 1-year OS.

Keywords: Durvalumab; Immune checkpoint inhibitors; NSCLC; Poor performance status; TRAE.