Schrödinger Reports Encouraging Phase 1 Data for SGR-1505 in Relapsed/Refractory B-cell Malignancies

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-12

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Schrödinger announced positive initial clinical data from a Phase 1 study of SGR-1505, an oral MALT1 inhibitor, in patients with relapsed/refractory B-cell malignancies. The drug demonstrated a favorable safety profile and encouraging preliminary efficacy. Responses were observed across various B-cell malignancies, including chronic lymphocytic leukemia (CLL) and Waldenström macroglobulinemia (WM). Dose escalation is complete, and Schrödinger plans to discuss the results with the FDA to determine the recommended Phase 2 dose. The data suggests SGR-1505 has potential as a best-in-class therapy for these cancers.

Key Highlights

  • SGR-1505 showed a favorable safety profile and was well-tolerated.
  • Encouraging preliminary efficacy was observed in patients with various B-cell malignancies.
  • Responses were seen in patients with CLL and Waldenström macroglobulinemia, even as monotherapy.
  • Dose escalation is complete, and discussions with the FDA regarding Phase 2 are planned.

Incidence and Prevalence

B-Cell Malignancies: Incidence and Prevalence

While several articles within the provided PubMed abstracts discuss various types of cancer and their respective incidence and prevalence rates, none specifically focus on B-cell malignancies as a distinct group on a global scale. The abstracts provide data on broader categories like hematologic malignancies or specific B-cell cancers like diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM), but comprehensive global figures for all B-cell malignancies are not available within these sources.

Hematologic Malignancies (including B-cell cancers):

  • Increasing Incidence: One study investigated hematologic malignancies (which include B-cell cancers) for the period 1990-2019. Globally, incident cases have been increasing since 1990, reaching 1,343.85 thousand in 2019. The burden is generally higher in men, with the gender gap decreasing after a certain age. Regional variations exist, with Central Europe, Eastern Europe, East Asia, and the Caribbean showing the largest increasing trends for different subtypes.
  • Declining Mortality: Despite rising incidence, the age-standardized death rate (ASDR) for all types of hematologic malignancies has been declining. In 2019, the ASDR for leukemia, multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma were 4.26, 1.42, 3.19, and 0.34 per 100,000 population, respectively. Hodgkin lymphoma showed the most significant decline.

Diffuse Large B-Cell Lymphoma (DLBCL):

  • Prevalence Estimates: A study using SEER data (2000-2018) estimated the US prevalence of DLBCL, accounting for cure rates. Estimates ranged from 63,883 to 142,889, depending on the assumed cure rate (52.8% to 68.9%) and timing of cure (1 to 20 years post-diagnosis). Without considering cure, the estimated prevalence was 179,475.

Multiple Myeloma (MM):

  • Growing Burden: Data from the 2021 Global Burden of Diseases study showed that global MM prevalence, incidence, mortality, and DALYs more than doubled between 1990 and 2021, especially among males. This increase was observed across all Social-Demographic Index (SDI) regions, with the middle SDI regions experiencing the fastest growth. Projections suggest a continued rise in the MM burden over the next 15 years.
  • Risk Factors: High body mass index (BMI) is a contributing factor to MM. The proportion of MM cases attributable to high BMI increased globally from 6.40% in 1990 to 7.96% in 2021.
  • Age Distribution: MM predominantly affects older adults, with the highest incidence and mortality rates in the 70-74 age group.

Conclusion:

While specific global incidence and prevalence data for all B-cell malignancies combined are not provided in the given abstracts, the information on related categories and specific B-cell cancers highlights the dynamic nature of these diseases. Further research and data collection are needed to provide a more comprehensive understanding of the global burden of B-cell malignancies as a whole.

Emerging Mechanism of Action

B-cell malignancies encompass a diverse group of cancers originating from different B-cell developmental stages, including lymphomas, leukemias, and plasma cell dyscrasias. Several key mechanisms of action (MoAs) have emerged as effective therapeutic strategies:

  • BTK Inhibition: Bruton's tyrosine kinase (BTK) plays a crucial role in B-cell receptor signaling, proliferation, and survival. Ibrutinib, a first-in-class BTK inhibitor, has demonstrated efficacy in treating various B-cell malignancies. However, off-target effects and resistance have led to the development of second- and third-generation BTK inhibitors like acalabrutinib, zanubrutinib, tirabrutinib, and orelabrutinib, which offer improved selectivity and potentially reduced side effects. These inhibitors work by covalently binding to BTK, disrupting its function. Zanubrutinib, for example, has shown a generally well-tolerated safety profile in a pooled analysis of 779 patients, with lower rates of atrial fibrillation, hypertension, and diarrhea compared to ibrutinib. Common adverse events included upper respiratory tract infection (39%), rash (27%), and bruising (25%).
  • Anti-CD20 Monoclonal Antibodies: Rituximab, a chimeric anti-CD20 monoclonal antibody, has significantly improved outcomes for B-cell malignancies since its approval. However, resistance and relapse have spurred the development of next-generation anti-CD20 antibodies like ofatumumab and obinutuzumab. These newer agents bind to distinct epitopes on CD20 or have modified Fc portions, leading to enhanced efficacy. Obinutuzumab, in particular, has demonstrated improved progression-free survival compared to rituximab in clinical trials. The emergence of rituximab biosimilars is also increasing global access to this therapy.
  • Bi-specific Antibodies: Blinatumomab, a bi-specific T-cell engager (BiTE) antibody, represents a novel immunotherapy approach. It binds to both CD19 on B cells and CD3 on T cells, redirecting the patient's T cells to eliminate CD19-expressing tumor cells. Clinical trials have shown blinatumomab's efficacy in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and B-cell non-Hodgkin's lymphoma. Odronextamab, another CD20xCD3 bispecific antibody, has shown promising antitumor activity in a phase 1 trial of 145 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, with an objective response rate of 51%.

These emerging MoAs offer promising treatment options for B-cell malignancies, particularly in cases of relapse/refractory disease. Ongoing research continues to explore novel agents and combination strategies to further improve patient outcomes.

Drug used in other indications

The provided text discusses the S1505 trial, which investigated neoadjuvant chemotherapy for resectable pancreatic ductal adenocarcinoma (PDA), not B-cell malignancies. The trial compared two chemotherapy regimens:

  • Arm 1: mFOLFIRINOX
  • Arm 2: gemcitabine/nab-paclitaxel

The study design was a randomized phase II trial. This means patients were randomly assigned to either Arm 1 or Arm 2, and the study was designed to assess the feasibility and efficacy of these treatments before potentially moving to a larger phase III trial. The trial enrolled 147 patients, but 44 (30%) were deemed ineligible. Of the 103 eligible patients, 77 (76%) completed preoperative therapy and underwent surgery. Of those who underwent surgery, 73 (95%) had successful resections. The study did not involve any other indications besides resectable PDA. It focused specifically on evaluating these two modern systemic therapies in a neoadjuvant/perioperative setting for this particular cancer.