STP938 for Lymphoma

Recruiting at 15 trial locations

Overseen By Maureen Higgins

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Step Pharma, SAS

Must not be taking: Monoclonal antibodies, others

Disqualifiers: Pregnancy, CNS involvement, Active malignancy, others

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

Compensation: Varies

Number of Visits: Unknown

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called STP938 (Dencatistat) for specific types of lymphoma, a cancer affecting the lymphatic system. The first part of the trial aims to determine the right dose by testing different amounts of the medication. The second part will assess the treatment's effectiveness for five types of B and T cell lymphomas. Individuals who have undergone at least two prior treatments for their lymphoma and have no other treatment options may be suitable for this study. As a Phase 1/Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had systemic cancer treatments or certain other therapies within 4 weeks before enrolling.

Is there any evidence suggesting that STP938 is likely to be safe for humans?

Research is testing the safety of STP938 for people with lymphoma, aiming to find a safe dose. Early studies focused on whether STP938 could be administered without causing serious harm.

STP938 blocks a protein called CTPS1, which cancer cells need to grow, making it harder for these cells to survive. Although specific safety results are not detailed, researchers are closely monitoring safety due to the early stage of research.

STP938 is taken orally, which can sometimes be easier on the body than injections. However, more information is needed to understand how well people tolerate it and what side effects it might cause. As the trial progresses, more details will become available. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma, which often include chemotherapy and targeted therapies like rituximab, STP938 is unique because it is administered as an oral monotherapy. This makes it potentially more convenient for patients who may prefer a pill over intravenous treatments. Researchers are also excited because STP938 may work through a novel mechanism of action, potentially targeting cancer cells differently than existing therapies. This could offer new hope for patients who haven't responded well to current options.

What evidence suggests that STP938 might be an effective treatment for lymphoma?

Research has shown that STP938 targets a molecule called CD38, found on many lymphoma cells, making it a promising treatment option. Additionally, STP938 blocks an enzyme called CTPS1, which cancer cells need to grow and multiply. By blocking this enzyme, STP938 can stop cancer cells from growing and eventually cause them to die. Although more information is needed, these actions suggest that STP938 could be effective against different types of B and T cell lymphomas. This trial includes a Phase 1 dose escalation arm to determine the best dosage and a Phase 2 expansion arm to further assess its safety and effectiveness in patients. ^{1 2 4 6 7}

Who Is on the Research Team?

Maureen Higgins

Principal Investigator

Step Pharma

Are You a Good Fit for This Trial?

Adults over 18 with B-cell or T-cell lymphoma that's come back or hasn't responded to treatment can join this trial. They must have tried at least two other treatments and have no other options left. Participants need good organ function, measurable disease, a decent performance status, and a life expectancy of more than three months.

Inclusion Criteria

My lymphoma has returned or didn't respond to treatment.

Life expectancy > 3 months as assessed by the Investigator

Signed and dated informed consent, and able to comply with the study procedures and any locally required authorization

Exclusion Criteria

I am not pregnant, breastfeeding, and if capable of childbearing or fathering a child, I agree to use contraception.

My cancer has spread to my brain or spinal cord.

I have had cancer within the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1: Dose Escalation

Participants receive STP938 as oral monotherapy to determine safety and optimal dosing

16 days

Multiple visits for dose escalation and monitoring

Phase 2: Cohort Expansion

Participants receive STP938 at defined dose levels to evaluate efficacy in different lymphoma types

9 months

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STP938

Trial Overview

STP938 is being tested in adults with certain types of lymphoma. The first phase will find the right dose of STP938 when used alone. The second phase will see how well it works on its own in different groups of patients with B and T cell lymphomas.

How Is the Trial Designed?

Group I: Phase 2 (Part 2; expansion) Experimental Treatment 1 Intervention

At defined dose level(s) with STP938 administered as oral monotherapy

Group II: Phase 1 (Part 1, Dose Escalation) Experimental Treatment 1 Intervention

Up to 5 dose levels with STP938 administered as oral monotherapy

Who Is Running the Clinical Trial?

Step Pharma, SAS

Lead Sponsor

Trials

3

Recruited

270+

Published Research Related to This Trial

The compound ST2825 effectively inhibits the growth of various lymphoma and leukaemia cell lines by inducing apoptosis and down-regulating key components of the NF-κB signaling pathway, including MYD88 and BTK.

ST2825 shows potential as a novel treatment for both B-lymphoid malignancies with MYD88 mutations and those with wild-type MYD88, indicating its broad applicability in targeting these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MYD88 Inhibitor ST2825 Suppresses the Growth of Lymphoma and Leukaemia Cells. Shiratori, E., Itoh, M., Tohda, S.[2017]

Pevonedistat, a selective NEDD8-activating enzyme inhibitor, effectively reduces the viability of canine diffuse large B-cell lymphoma (DLBCL) cells by inducing G1 cell cycle arrest and apoptosis, targeting the deregulated NF-κB pathway.

In vivo studies demonstrated that pevonedistat administration led to significant tumor regression in mice with canine DLBCL xenograft tumors, supporting its potential as a novel anti-cancer therapy for both dogs and humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting NEDD8-activating enzyme is a new approach to treat canine diffuse large B-cell lymphoma. Assumpção, ALFV., Lu, Z., Marlowe, KW., et al.[2023]

CD38, an enzyme on lymphocytes, can stimulate strong cell growth when combined with other factors, but B cells from xid mice do not respond to this stimulation, indicating a signaling defect.

The unresponsiveness of xid B cells to CD38 stimulation suggests that Bruton's tyrosine kinase (btk) plays a crucial role in the signaling pathway necessary for this response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38 unresponsiveness of xid B cells implicates Bruton's tyrosine kinase (btk) as a regular of CD38 induced signal transduction. Santos-Argumedo, L., Lund, FE., Heath, AW., et al.[2019]

P38α/β plays a crucial role in the proliferation and survival of acute lymphoblastic leukemia (ALL), with its activation linked to the growth of leukemia cells and associated with relapses in patients with TEL-AML1-positive leukemia.

Inhibition of p38α/β using small molecules has been shown to suppress leukemic growth and improve survival in experimental models, suggesting that targeting this pathway could enhance the effectiveness of existing leukemia treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of p38α/β inhibition on acute lymphoblastic leukemia proliferation and survival in vivo. Alsadeq, A., Strube, S., Krause, S., et al.[2018]

LP-284, a new-generation acylfulvene compound, shows strong potential in treating non-Hodgkin's lymphoma (NHL) by inducing repair of double-strand DNA breaks and demonstrating nanomolar potency across fifteen NHL cell lines.

In vivo studies revealed that LP-284 significantly prolongs survival in mice with mantle cell lymphoma, outperforming existing treatments like bortezomib and ibrutinib, and effectively inhibits tumor growth in cases resistant to these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LP-284, a small molecule acylfulvene, exerts potent antitumor activity in preclinical non-Hodgkin's lymphoma models and in cells deficient in DNA damage repair. Zhou, J., Sturtevant, D., Love, C., et al.[2023]

CD38 is a promising target for antibody therapy in various lymphoid tumors, including multiple myeloma, due to its strong presence on tumor cell surfaces.

Recent advancements in anti-CD38 antibodies have shown potent cytolytic effects against myeloma cells, with some antibodies also inhibiting CD38's cyclase activity, enhancing their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD38 as a therapeutic target. Stevenson, GT.[2018]

Recent advances in understanding B-cell lymphomas have led to the development of new therapeutic agents that target specific tumor cell signaling pathways and microenvironments, enhancing treatment options.

The review highlights various innovative therapies, including B-cell receptor pathway inhibitors, Bcl-2 inhibitors, monoclonal antibodies, and CAR T-cell therapies, which show promise based on recent clinical data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Breakthrough therapies in B-cell non-Hodgkin lymphoma. Cheah, CY., Fowler, NH., Wang, ML.[2020]

In a study using SCID mice injected with the aggressive Burkitt's lymphoma cell line Ramos, treatment with anti-CD19 and anti-CD38 immunotoxins significantly prolonged survival compared to controls, with the anti-CD38 immunotoxin showing the greatest effect.

Combining both immunotoxins resulted in a remarkable therapeutic outcome, with 20% of treated mice surviving disease-free for up to 300 days, suggesting that targeting both CD19 and CD38 could be an effective strategy for treating B-cell lymphomas and acute lymphoblastic leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of human B-cell lymphoma bearing SCID mice is more effective with anti-CD19- and anti-CD38-saporin immunotoxins used in combination than with either immunotoxin used alone. Flavell, DJ., Boehm, DA., Emery, L., et al.[2019]

Pevonedistat, a NEDD8-activating enzyme inhibitor, effectively induced cell death in activated B-cell diffuse large B-cell lymphoma (DLBCL) cell lines and inhibited NFκB activity, suggesting a promising mechanism of action against this type of cancer.

In pre-clinical models, pevonedistat enhanced the effectiveness of several chemotherapy agents and targeted therapies, leading to prolonged survival in mice when combined with ibrutinib or cytarabine, indicating its potential as a valuable treatment option in DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pevonedistat, a NEDD8-Activating Enzyme Inhibitor, Induces Apoptosis and Augments Efficacy of Chemotherapy and Small Molecule Inhibitors in Pre-clinical Models of Diffuse Large B-cell Lymphoma. Torka, P., Mavis, C., Kothari, S., et al.[2022]

Advances in genomic and proteomic technologies have identified new biomarkers and drug targets for aggressive B- and T-cell non-Hodgkin's lymphomas (NHLs), but the development of effective therapies has been slow due to the absence of a therapeutic signature for these subtypes.

Promising new therapies are being developed that target key oncogenic pathways involved in NHL, including immune kinases and apoptosis, with a focus on creating a therapeutic signature based on the 10 hallmarks of cancer to guide future drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutics for aggressive non-Hodgkin's lymphoma. Mahadevan, D., Fisher, RI.[2021]

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05463263

NCT05463263 | A Phase 1/2 Study of STP938 for Adult ...

The main outcome of the first part of the study is to see if STP938 can be given safely to patients with lymphoma, and to work out the best dose of STP938. The ...

2.

cancer.gov

cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-10514

A Phase 1/2 Study of STP938 for Adult Subjects With ...

The main outcome of. the second part of the study is to see if ST938 is effective in treating different types. of lymphoma. Trial Phase & Type. Trial PhasePhase ...

3.

step-ph.com

step-ph.com/step-pharma-announces-first-participant-dosed-in-a-phase-1b-clinical-trial-of-dencatistat-for-essential-thrombocythaemia/

Step Pharma announces first participant dosed in a phase ...

CTPS1 inhibition blocks the proliferation of cancer cells and results in cell death. All cancers appear to be addicted to CTPS1 for DNA ...

4.

withpower.com

withpower.com/trial/phase-2-lymphoma-t-cell-6-2022-8dc58

STP938 for Lymphoma · Recruiting Participants for Phase ...

STP938 is unique because it targets the CD38 molecule, which is present on many lymphoma cells, making it a promising option for antibody therapy.

5.

step-ph.com

step-ph.com/step-pharma-announces-first-patient-dosed-in-a-phase-1-trial-of-dencatistat-for-patients-with-solid-tumours/

Step Pharma announces first patient dosed in a phase 1 ...

CTPS1 inhibition blocks the proliferation of cancer cells and results in cell death. All cancers appear to be addicted to CTPS1 for DNA ...

6.

step-ph.com

step-ph.com/step-pharma-announces-us-fda-clearance-for-a-phase-i-clinical-trial-in-solid-tumours-with-dencatistat-stp938/

+ Dencatistat

The open label trial will evaluate the safety, tolerability and pharmacokinetics of dencatistat in adults living with advanced solid tumours.

7.

sygnaturediscovery.com

sygnaturediscovery.com/news-and-events/blog/lymphoma-treatment-enters-clinical-phase/

Novel Lymphoma Treatment Enters Clinical Phase

The dose-escalating part of the trial aims to assess the safety and tolerability of STP938 in adult subjects with relapsed/refractory B cell and T cell ...