A First-in-Human Study of ATM Inhibitor Lartesertib as Monotherapy in Patients with Advanced Solid Tumors.

Purpose: This first-in-human Phase 1, open-label study (NCT04882917) evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and maximum tolerated dose (MTD) of the highly potent and selective oral ataxia‑telangiectasia mutated (ATM) kinase inhibitor lartesertib.

Patients And Methods: Patients with advanced solid tumors received oral doses of lartesertib for a dose range of 100-400 mg once daily (QD). Dose-escalation was based on PK, PD, and safety data guided by a Bayesian 2-parameter logistic regression model.

Microtracer-Based Assessment of the Mass Balance, Pharmacokinetics, and Excretion of [C]Berzosertib, an Intravenous ATR Inhibitor, in Patients With Advanced Solid Tumors: A Phase 1 Study.

Berzosertib is a small-molecule ataxia telangiectasia and Rad3-related protein inhibitor. To assess the clearance mechanism(s) of berzosertib, a Phase 1, 2-period, open-label study was conducted in adults with advanced solid tumors who were treated with a single intravenous dose of 210 mg/m berzosertib containing approximately 3 µCi of [C]berzosertib (Period 1 Mass Balance), followed by assessment of berzosertib in combination with topotecan (Period 2 [Extension]) (NCT05246111). A total of 6 patients were enrolled in Period 1; 5 of them rolled over to Period 2.

Sustained inhibition of complement C1s with sutimlimab over 2 years in patients with cold agglutinin disease.

Cold agglutinin disease (CAD) is a rare, autoimmune, classical complement pathway (CP)-mediated hemolytic anemia. Sutimlimab selectively inhibits C1s of the C1 complex, preventing CP activation while leaving the alternative and lectin pathways intact. In Part A (26 weeks) of the open-label, single-arm, Phase 3 CARDINAL study in patients with CAD and a recent history of transfusion, sutimlimab demonstrated rapid effects on hemolysis and anemia.