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Войти в исследования British journal of cancer · 2026
Phase Ib trial of SL-172154, a bispecific CD47 inhibitor and CD40 agonist Fc-fusion protein, in combination with mirvetuximab soravtansine or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод в очереди
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Drew Yvette, Gilbert Lucy, Martinez Bueno Alejandro, Oaknin Ana, Moreno Victor, Gaba Garcia Lydia, Jayson Gordon C, Kristeleit Rebecca S, Lakhani Nehal, Banerjee Susana, Matei Daniela, Oza Amit, Miller Rowan, Yiannakis Dennis, Barretina-Ginesta Maria-Pilar, Martínez García Jerónimo, Wang Guanfang, Miriyala Jayalakshmi, Franke Amy, Galvez Elisa, Pandite Lini, Richardson Debra L
Аннотация
BACKGROUND: Platinum resistant ovarian cancer (PROC) is associated with poor survival. This clinical trial sought to determine whether the bispecific CD47 inhibitor and CD40 agonist, SL-172154, could be combined safely and improve the efficacy of mirvetuximab (MIRV) or pegylated liposomal doxorubicin (PLD) through enhanced tumor cell phagocytosis and antigen presentation to T cells.
METHODS: Patients with PROC received MIRV (21-day cycle) or PLD (28-day cycle) on day 1 and SL-172154 (3 mg/kg) on days 8 and 15 of each cycle. Objectives included safety, anti-tumor activity, PK, and immunogenicity.
RESULTS: 65 patients (60% folate receptor alpha (FRα) high and 40% medium/low) were enrolled in the MIRV cohort and 21 patients in the PLD cohort. Most common TEAEs ( > 40%) in the MIRV cohort were blurred vision, nausea, infusion related reaction, transaminase increase, diarrhea, and in the PLD cohort, nausea, constipation, neutropenia and fatigue. The objective response rate in the MIRV cohort was 33% (95% CI, 19%, 50%) for FRα high subgroup, and 15% (95% CI, 4%, 35%) for FRα medium/low subgroup, and in the PLD cohort was 20% (95% CI, 6%, 44%).
CONCLUSIONS: Combination of SL172154 with MIRV did not improve upon the previously reported ORR for MIRV, while the combination with PLD resulted in a higher ORR than reported for PLD, albeit in a small number of patients. Limited tumor penetration of SL-172154, lack of durable CD47 blockade, inability to overcome T cell exhaustion and other mechanisms of resistance may explain these findings. Trial register number: NCT05483933.
METHODS: Patients with PROC received MIRV (21-day cycle) or PLD (28-day cycle) on day 1 and SL-172154 (3 mg/kg) on days 8 and 15 of each cycle. Objectives included safety, anti-tumor activity, PK, and immunogenicity.
RESULTS: 65 patients (60% folate receptor alpha (FRα) high and 40% medium/low) were enrolled in the MIRV cohort and 21 patients in the PLD cohort. Most common TEAEs ( > 40%) in the MIRV cohort were blurred vision, nausea, infusion related reaction, transaminase increase, diarrhea, and in the PLD cohort, nausea, constipation, neutropenia and fatigue. The objective response rate in the MIRV cohort was 33% (95% CI, 19%, 50%) for FRα high subgroup, and 15% (95% CI, 4%, 35%) for FRα medium/low subgroup, and in the PLD cohort was 20% (95% CI, 6%, 44%).
CONCLUSIONS: Combination of SL172154 with MIRV did not improve upon the previously reported ORR for MIRV, while the combination with PLD resulted in a higher ORR than reported for PLD, albeit in a small number of patients. Limited tumor penetration of SL-172154, lack of durable CD47 blockade, inability to overcome T cell exhaustion and other mechanisms of resistance may explain these findings. Trial register number: NCT05483933.