SGR-1505 Earns Fast Track Designation for R/R Waldenström Macroglobulinemia

Among 5 patients with Waldenström macroglobulinemia evaluable for efficacy in a phase 1 dose escalation trial, all had responded, and responses included 2 partial responses and 3 minor responses.

The FDA has granted SGR-1505, a clinical stage MALT1 inhibitor, fast track designation for the treatment of adult patients with Waldenström macroglobulinemia who have progressed following at least 2 lines of prior therapy, including a Bruton’s tyrosine kinase (BTK) inhibitor, according to a news release from the drug’s developer, Schrödinger, Inc.¹

Support for the FDA’s decision follows results from a phase 1 dose escalation trial (NCT05544019) evaluating SGR-1505 as a monotherapy treatment in patients with relapsed/refractory B-cell malignancies. Results from the trial were exhibited in a poster presentation at the European Hematology Association (EHA) 2025 Congress.²

Data revealed that, among 49 patients with B-cell malignancies, including 6 patients with Waldenström macroglobulinemia, SGR-1505 was well-tolerated with no dose-limiting toxicities or treatment-emergent adverse effect (TEAE)-related deaths observed in the study. A total of 21 (43%) patients experienced at least 1 treatment-related AE (TRAE), with the most common TRAEs including rash (14%) and fatigue (12%). A total of 10 patients (20%) experienced treatment-emergent serious AEs (SAEs), 1 of which was related to study treatment and included a grade 3 instance of herpes simplex reactivation.

Additionally, preliminary efficacy data revealed that the agent was clinically active in numerous relapsed/refractory B-cell malignancies.Of 45 patients with at least 1 follow-up disease assessment or progression evaluable for efficacy, the overall response rate (ORR) was 22% (n = 10/45). Furthermore, among patients with Waldenström macroglobulinemia evaluable for efficacy (n = 5), all had responded, and responses included 2 partial responses and 3 minor responses. They were all previously treated with prior BTK inhibition.

“We are excited to receive fast track designation for SGR-1505, which underscores the significant need in patients with Waldenström macroglobulinemia,” Karen Akinsanya, PhD, president, head of therapeutics R&D, and chief strategy officer of partnerships at Schrödinger, said in the news release.¹ “Despite the continued therapeutic advances in the treatment of hematologic malignancies, treatment failure and disease progression due to BTK resistance remains a challenge for a growing number of patients. This unmet need represents an opportunity for novel mechanisms such as MALT1 as monotherapy and as part of new combination regimens.”

Adult patients with relapsed/refractory B-cell malignancies received SGR-1505 monotherapy orally at escalating doses in a 3+3 design. Patients in cohort A received the study drug daily starting at 50 mg up to 400 mg and those in cohort B received it twice daily starting at 50 mg up to 200 mg.

The median age of patients on study was 64 years (range, 31-82), and 65.3% of patients were male. A total of 51.0% of patients had an ECOG performance score of 0, and the median number of prior lines of therapy was 4 (range, 2-9). The most common histologies included chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL; 36.7%) and diffuse large B-cell lymphoma (DLBCL;18.4%), and patients most commonly received prior BTK inhibition (55.1%) and anti-CD20 monoclonal antibodies (93.9%).

The primary end points included safety and tolerability, as well as identifying the maximum tolerated dose, maximum administered dose, and/or recommended doses. Secondary end points included pharmacokinetics and preliminary anti-tumor monotherapy activity. An exploratory end point was pharmacodynamics.

Of note, 13 patients were still receiving treatment after at least 120 days, including 3 who had received ongoing treatment for greater than 1 year as of data cutoff. Additionally, 1 patient with Waldenström macroglobulinemia treated with 50 mg daily SGR-1505 was receiving ongoing treatment after more than 2 years (752+ days).

“We believe this fast track designation in Waldenström macroglobulinemia, combined with our encouraging phase 1 data across a broad range of relapsed/refractory B-cell malignancies such as [CLL], [DLBCL], and marginal zone lymphoma, reinforce the potential of SGR-1505 as a future therapeutic option for patients," Margaret Dugan, MD, chief medical officer at Schrödinger, stated in the news relase.¹ “We look forward to discussing our phase 1 study results and recommended phase 2 dose with the FDA later this year.”

References

1. Schrödinger receives fast track designation for SGR-1505 for the treatment of relapsed/refractory Waldenström macroglobulinemia. News release. Schrödinger, Inc. June 27, 2025. Accessed June 30, 2025. https://tinyurl.com/46ke5vfc
2. Spurgeon S, Musteata V, Karnabeda O, et al. A phase 1 study of SGR-1505, an oral, potent MALT1 inhibitor for relapsed/refractory (R/R) B-cell malignancies, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Poster 1570.