SGR-1505 for B-Cell Lymphoma

Recruiting at 17 trial locations

Overseen By Study Physician

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Schrödinger, Inc.

Disqualifiers: Immediate cytoreductive therapy, Invasive malignancy, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

52 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing SGR-1505, a new oral drug that blocks a protein called MALT1, in patients with B-cell lymphomas that have returned or did not respond to previous treatments. The goal is to find the safest and most effective dose while also seeing how well it works against the cancer.

Do I have to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug SGR-1505 for B-Cell Lymphoma?

The research mentions YM155, a drug similar to SGR-1505, which shows strong antitumor activity against aggressive non-Hodgkin lymphoma, including B-cell lymphoma, by inhibiting tumor growth and increasing survival in models. This suggests that SGR-1505 might also be effective due to its potential similarities with YM155. ^{1 2 3 4 5}

What makes the drug SGR-1505 unique for treating B-cell lymphoma?

SGR-1505 is unique because it may target specific pathways involved in B-cell lymphoma, such as those related to the B-cell receptor, which are not effectively addressed by standard treatments like R-CHOP. This could potentially improve outcomes for patients with certain subtypes of B-cell lymphoma, such as CD5+ DLBCL, which have poorer prognoses with existing therapies. ^{1 3 6 7 8}

Research Team

Frank G Basile, M.D.

Principal Investigator

Schrodinger Inc.

Eligibility Criteria

This trial is for people with various types of mature B-cell cancers, like lymphoma and leukemia. Participants must have a confirmed diagnosis, measurable disease, be relatively active (ECOG 0-2), and expected to live at least 12 weeks. They can't join if they've had another cancer in the last 2 years or need immediate treatment for indolent NHL/CLL unless out of options.

Inclusion Criteria

Life expectancy ≥ 12 weeks.

My disease can be measured or detected with tests.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I had cancer that spread into surrounding tissues within the last 2 years.

My cancer has spread to my brain and is causing symptoms.

Subject has a known allergy to SGR-1505 or excipients of SGR-1505.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive SGR-1505 across up to 9 dose levels to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD)

21 days

Multiple visits for dose escalation and monitoring

Exploratory Cohorts

Evaluation of additional pharmacokinetics, pharmacodynamics, preliminary anti-tumor activity, and safety to establish the recommended dose (RD) of SGR-1505

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• SGR-1505

Trial Overview The study is testing SGR-1505's safety and how well patients tolerate it. It aims to find the highest dose patients can handle without severe side effects (MTD) or suggest an optimal dose for further research (RD).

Participant Groups

Group I: Dose Escalation Experimental Treatment 1 Intervention

Up to 9 dose levels in total will be evaluated across two dosing schedules. Eligible patients will be assigned to a dose level cohort according to an accelerated titration design that will transition to a traditional 3+3 dose escalation.

Who Is Running the Clinical Trial?

Schrödinger, Inc.

Lead Sponsor

Trials

3

Recruited

150+

Findings from Research

Serum levels of soluble CD155 (sCD155) are significantly higher in patients with diffuse large B cell lymphoma (DLBCL) at diagnosis compared to healthy controls, indicating its potential role as a biomarker for this cancer.

Elevated sCD155 levels are associated with a lack of response to the standard treatment regimen CHOP with or without rituximab, suggesting that sCD155 could be a prognostic indicator for treatment outcomes in DLBCL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of serum soluble CD155 level at diagnosis on interim response to CHOP with or without rituximab in diffuse large B cell lymphoma. Azzazi, MO., Hegab, HM., El-Ghammaz, AMS., et al.[2022]

YM155 effectively inhibits the growth of aggressive non-Hodgkin lymphoma, showing 50% growth inhibition in various diffuse large B-cell lymphoma cell lines at concentrations between 0.23 and 3.9 nM.

In in vivo models, continuous infusion of YM155 not only eradicated established tumors but also significantly improved survival compared to the standard treatment rituximab, suggesting its potential as a promising therapy for aggressive lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effects of YM155, a novel survivin suppressant, against human aggressive non-Hodgkin lymphoma. Kita, A., Nakahara, T., Yamanaka, K., et al.[2022]

CD5+ diffuse large B-cell lymphoma (DLBCL) is associated with poorer outcomes compared to non-CD5+ DLBCL, often affecting older female patients with advanced disease and a high risk of central nervous system relapse.

Traditional treatments like R-CHOP are less effective for CD5+ DLBCL, but higher-dose therapies such as R-DA-EPOCH and novel drugs like lenalidomide show promise in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances. Xu, Y., Sun, W., Li, F.[2021]

In a phase II study involving 41 patients with refractory diffuse large B-cell lymphoma (DLBCL), YM155 showed limited efficacy as a single agent, achieving a complete remission in only 2.4% of patients and a median progression-free survival of 58 days.

YM155 was well tolerated overall, with the most common side effects being anemia and fatigue, suggesting it may be safer for patients, but its effectiveness may improve when combined with other treatments like rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma. Cheson, BD., Bartlett, NL., Vose, JM., et al.[2022]

Bruton's tyrosine kinase (BTK) inhibitors, particularly ibrutinib, have shown excellent response rates and a favorable safety profile, making them a strong candidate for frontline therapy in certain types of B cell non-Hodgkin lymphomas (NHLs).

While PI3K inhibitors can be effective for some relapsed lymphomas, their use is often limited by side effects, highlighting the need for ongoing research to improve treatment options and address resistance to BTK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting the B cell receptor pathway in non-Hodgkin lymphoma. Valla, K., Flowers, CR., Koff, JL.[2019]

The study analyzed gene expression in 90 DLBCL patients, revealing that all CD5-positive DLBCL cases were classified as activated B-cell-like (ABC) DLBCL, which is associated with a poor prognosis and high rates of CNS relapse.

The identification of SH3BP5 as a key gene related to CD5 expression suggests that targeting ABC DLBCL therapeutic strategies could be beneficial for treating CD5(+) DLBCL, potentially addressing the underlying causes of its aggressive nature.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene expression profiling of diffuse large B-Cell lymphomas supervised by CD5 expression. Miyazaki, K., Yamaguchi, M., Imai, H., et al.[2018]

Disruption of B cell receptor signaling is crucial for treating B cell lymphomas, as it can lead to the death of malignant B cells, highlighting the importance of targeting this pathway.

Small molecule tyrosine kinase inhibitors, such as those targeting Syk, BTK, and PI3K, show promising results in clinical trials for patients with relapsed and refractory B cell lymphomas, indicating their potential efficacy in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The future of B-cell lymphoma therapy: the B-cell receptor and its downstream pathways. Kenkre, VP., Kahl, BS.[2021]

A new risk scoring system for diffuse large B-cell lymphoma (DLBCL) was developed using data from 197 patients, combining clinical and biological factors to predict overall and progression-free survival, with significant hazard ratios ranging from 0.15 to 5.49.

This scoring system was validated in an independent group of 166 DLBCL patients, demonstrating its potential to improve treatment personalization and outcomes for patients receiving R-CHOP immunochemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated prognostic model for diffuse large B-cell lymphoma treated with immunochemotherapy. Rodríguez, M., Alonso-Alonso, R., Fernández-Miranda, I., et al.[2022]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Impact of serum soluble CD155 level at diagnosis on interim response to CHOP with or without rituximab in diffuse large B cell lymphoma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Antitumor effects of YM155, a novel survivin suppressant, against human aggressive non-Hodgkin lymphoma. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

De Novo CD5+ Diffuse Large B-Cell Lymphoma: Biology, Mechanism, and Treatment Advances. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

A phase II study of the survivin suppressant YM155 in patients with refractory diffuse large B-cell lymphoma. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Targeting the B cell receptor pathway in non-Hodgkin lymphoma. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Gene expression profiling of diffuse large B-Cell lymphomas supervised by CD5 expression. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

The future of B-cell lymphoma therapy: the B-cell receptor and its downstream pathways. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

An integrated prognostic model for diffuse large B-cell lymphoma treated with immunochemotherapy. [2022]