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A WIN Consortium phase I study exploring avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer Callejo Perez, Ana Berchem, Guy Bazhenova, Lyudmila Saintigny, Pierre Solomon, Benjamin Bar, Jair Felip Font, Enriqueta Institut Català de la Salut [Solomon B] Avera Cancer Institute, Sioux Falls, South Dakota, USA. [Callejo A, Felip E] Vall d'Hebron Hospital Universitari, Barcelona, Spain. Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. [Bar J] Chaim Sheba Medical Center, Tel Hashomer, Israel. [Berchem G] Centre Hospitalier de Luxembourg, Luxembourg Institute of Health, Luxembourg City, Luxemburg. [Bazhenova L] University of California San Diego, Moores Cancer Center, San Diego, California, USA. [Saintigny P] Centre Léon Bérard, Cancer Research Center of Lyon, University of Lyon, Lyon, France Vall d'Hebron Barcelona Hospital Campus Pulmons - Càncer - Tractament Quimioteràpia combinada DISEASES::Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Carcinoma, Non-Small-Cell Lung Other subheadings::Other subheadings::Other subheadings::/drug therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma de pulmón de células no pequeñas Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada Genomics; Transcriptomics; Lung cancer Genómica; Transcriptómica; Cáncer de pulmón Genòmica; Transcriptòmica; Càncer de pulmó Background The Worldwide Innovative Network (WIN) Consortium has developed the Simplified Interventional Mapping System (SIMS) to better define the cancer molecular milieu based on genomics/transcriptomics from tumor and analogous normal tissue biopsies. SPRING is the first trial to assess a SIMS-based tri-therapy regimen in advanced non-small cell lung cancer (NSCLC). Methods Patients with advanced NSCLC (no EGFR, ALK, or ROS1 alterations; PD-L1 unrestricted; ≤2 prior therapy lines) received avelumab, axitinib, and palbociclib (3 + 3 dose escalation design). Results Fifteen patients were treated (five centers, four countries): six at each of dose levels 1 (DL1) and DL2; three at DL3. The most common ≥Grade 3 adverse events were neutropenia, hypertension, and fatigue. The recommended Phase II dose (RP2D) was DL1: avelumab 10 mg/kg IV q2weeks, axitinib 3 mg po bid, and palbociclib 75 mg po daily (7 days off/21 days on). Four patients (27%) achieved a partial response (PR) (progression-free survival [PFS]: 14, 24, 25 and 144+ weeks), including two after progression on pembrolizumab. Four patients attained stable disease (SD) that lasted ≥24 weeks: 24, 27, 29, and 64 weeks. At DL1 (RP2D), four of six patients (66%) achieved stable disease (SD) ≥6 months/PR (2 each). Responders included patients with no detectable PD-L1 expression and low tumor mutational burden. Conclusions Overall, eight of 15 patients (53%) achieved clinical benefit (SD ≥ 24 weeks/PR) on the avelumab, axitinib, and palbociclib combination. This triplet showed antitumor activity in NSCLC, including in tumors post-pembrolizumab progression, and was active at the RP2D, which was well tolerated. This work was supported by the ARC Foundation for Cancer Research, Villejuif, France and Worldwide Innovative Network (WIN) Association––WIN Consortium, Villejuif, France, sponsor of the study. WIN was responsible for the study design, collection, analysis, and interpretation of data as well as writing of the report. The study drugs were provided by Pfizer, as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer. Funded in part by National Cancer Institute grant P30 CA023100 and the Joan and Irwin Jacobs Fund philanthropic fund (RK). 2022-08-12T10:47:07Z 2022-08-12T10:47:07Z 2022-07 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Solomon B, Callejo A, Bar J, Berchem G, Bazhenova L, Saintigny P, et al. A WIN Consortium phase I study exploring avelumab, palbociclib, and axitinib in advanced non-small cell lung cancer. Cancer Med. 2022 Jul;11(14):2790–800. 2045-7634 https://hdl.handle.net/11351/8001 10.1002/cam4.4635 35307972 000776243800001 eng Cancer Medicine;11(14) https://doi.org/10.1002/cam4.4635 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Wiley Scientia