TIGOS-LS, an open-label, randomized study of BMS-986489 (atigotatug + nivolumab fixed-dose combination) vs durvalumab as consolidation therapy following chemoradiotherapy in limited-stage small-cell lung cancer.

Abstract

TPS8134 Background: Durvalumab consolidation was added to concurrent chemoradiotherapy for standard-of-care treatment of limited-stage small-cell lung cancer (LS-SCLC) in 2024. Although durvalumab improves overall survival (OS) and progression-free survival (PFS; Cheng et al. 2024), other agents may provide further improvement. BMS-986489 is a first-in-class fixed-dose combination of atigotatug and nivolumab. Atigotatug binds to fucosyl-monosialoganglioside-1 (fuc-GM1), which is highly expressed on SCLC cells and often absent in normal tissues. This binding causes tumor cell death via antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis, or complement-dependent cytotoxicity. These processes trigger T cells, whose activation is also potentiated by nivolumab, which is hypothesized to improve outcomes after chemoradiotherapy. In a randomized Phase II study in extensive-stage SCLC, adding atigotatug to carboplatin, etoposide, and nivolumab (CE/NIVO) improved median OS vs CE/NIVO alone (15.6 months vs 11.4 months; Kalinka et al. 2024). Methods: TIGOS-LS is an open-label, randomized study evaluating the safety and efficacy of BMS-986489 vs durvalumab consolidation after chemoradiotherapy in LS-SCLC. Approximately 250 participants will be enrolled at 70 sites within the US. Eligible participants are adults with an Eastern Cooperative Oncology Group performance status of 0 or 1, histologically or cytologically confirmed SCLC evaluable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 before standard treatment was initiated, LS disease determined by PET scan at the time of initial diagnosis or justified by the participant history, and inoperable disease, if Stage I/II. All participants must have completed concurrent chemoradiotherapy without progression. Prophylactic cranial irradiation (PCI) is permitted before study treatment. Expression of fuc-GM1 is not required; participants can enroll regardless of tissue availability for the trial. Participants requiring chronic systemic corticosteroids equivalent to >10 mg of prednisone at the time of enrollment are excluded. Stratification factors include disease stage (I/II vs III) and receipt of PCI. Randomization is 1:1 to BMS-986489 or durvalumab. BMS-986489 or durvalumab is administered intravenously at a fixed dose once every 4 weeks for up to 2 years or until discontinuation criteria are met. Response is evaluated by RECIST v1.1. Survival follow-up occurs every 12 weeks for up to 3 years. The primary endpoint is OS. Secondary endpoints include PFS, objective response rate, clinical benefit rate, disease control rate, duration of response, and safety parameters. TIGOS-LS (NCT06773910) opened to enrollment in March 2025; 232 enrollment slots remain. Clinical trial information: NCT06773910 .