ST-067 + Teclistamab for Multiple Myeloma

Overseen By Rahul Banerjee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Washington

Must be taking: Teclistamab

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Prior BCMA therapy, Active infection, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of combining two treatments, ST-067 (Decoy-Resistant IL-18) and teclistamab, for multiple myeloma, a type of blood cancer that has either returned after treatment or not responded to previous therapies. ST-067 is designed to help the immune system target and kill cancer cells, while teclistamab disrupts cancer cell growth by binding to specific proteins on the cells. The trial seeks participants with multiple myeloma who have undergone at least four different treatments and still have active disease. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot use other anti-multiple myeloma drugs within 7 days of screening. Also, you cannot take certain steroids or immunosuppressive medications within 14 days of starting the study drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining ST-067 and teclistamab might be safe and manageable for people with relapsed or refractory multiple myeloma, indicating that severe side effects are unlikely. Early results suggest that ST-067 can enhance the immune system's response when used with teclistamab. Both treatments assist the immune system in identifying and destroying cancer cells. As this trial is in its early stages, it primarily aims to assess safety and determine the optimal dose. Although detailed information is limited, the trial's existence suggests that earlier studies have demonstrated some level of safety for these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ST-067 and Teclistamab for treating multiple myeloma because these treatments bring novel mechanisms to the table. Unlike standard therapies that commonly target cancer cells directly or modulate the immune system in broader ways, ST-067 is a novel agent that might offer a new way of harnessing the body's immune response against myeloma cells. Teclistamab, on the other hand, is a bispecific antibody that specifically targets two different markers on cancer cells and immune cells, potentially leading to a more focused and potent attack on the cancer. This dual approach could provide more effective treatment options by enhancing the body's ability to identify and destroy myeloma cells.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that teclistamab, one of the treatments in this trial, may help treat relapsed or refractory multiple myeloma, a type of blood cancer. In studies, 63% of patients responded to teclistamab, meaning their cancer shrank or disappeared. On average, patients lived 4.8 months without their disease worsening, and 60% were still alive after 9 months.

ST-067, another treatment in this trial, is a new therapy designed to strengthen the immune system to fight cancer. It avoids being blocked by certain proteins, which helps it remain effective. Although information on ST-067's effects in humans is limited, early research is promising. The trial aims to combine ST-067 with teclistamab to further boost the immune response. ^{1 4 6 7 8}

Who Is on the Research Team?

Rahul Banerjee, MD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has either returned after a period of remission or hasn't improved with previous treatments. Specific eligibility details are not provided, but typically participants must meet certain health standards and may be required to have specific characteristics related to their condition.

Inclusion Criteria

Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min

My multiple myeloma meets specific medical criteria.

I am able to get out of my bed or chair and move around.

Exclusion Criteria

My multiple myeloma has spread to my brain or spinal cord.

I have been in remission from any other cancer for at least 1 year.

Current or planned pregnancy or breastfeeding within the next 12 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Patients receive ST-067 and teclistamab subcutaneously in a dose-escalation and dose-expansion study. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 5 years

Multiple visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-ups every 3 months.

Up to 5 years

Every 3 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• ST-067
• Teclistamab

Trial Overview The trial is testing the safety and optimal dosage of ST-067 combined with teclistamab in treating relapsed or refractory multiple myeloma. ST-067 enhances immune response against cancer cells, while teclistamab targets proteins on B-cells and T-cells potentially inhibiting cancer growth.

How Is the Trial Designed?

Group I: Treatment (ST-067, teclistamab) Experimental Treatment 6 Interventions

Patients receive ST-067 SC on days 1, 8, 15 and 22 of cycle 1, on days 8, 15 and 22 of cycle 2, then on days 1 and 15 of subsequent cycles. Patients also receive teclistamab SC on days 1, 3, 5, 15 and 22 of cycle 2 then on days 1, 8, 15, and 22 or days 1 and 15 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection throughout the trial and bone marrow aspiration and biopsy during screening and on study.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Simcha Therapeutics

Collaborator

Trials

2

Recruited

40+

Published Research Related to This Trial

In a phase 1-2 study involving 165 patients with relapsed or refractory multiple myeloma, teclistamab demonstrated a high overall response rate of 63%, with 39.4% achieving a complete response, indicating its efficacy as a treatment option for heavily pre-treated patients.

While teclistamab showed promising results, common adverse effects included cytokine release syndrome (72.1% of patients) and neutropenia (70.9%), though most toxicities were grade 1 or 2, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab in Relapsed or Refractory Multiple Myeloma. Moreau, P., Garfall, AL., van de Donk, NWCJ., et al.[2023]

Teclistamab-cqyv is a bispecific T-cell engager antibody that effectively activates the immune system to target multiple myeloma cells, showing an overall response rate of over 60% in heavily pretreated patients.

The side effect profile of teclistamab-cqyv is more tolerable compared to other BCMA-targeted therapies, making it a suitable treatment option for elderly patients with relapsed or refractory multiple myeloma, and it has received FDA approval for use as monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. Hua, G., Scanlan, R., Straining, R., et al.[2023]

Teclistamab-cqyv is an FDA and EMA-approved bispecific antibody that effectively targets multiple myeloma (MM) by engaging T cells to attack cancer cells, showing a 60% overall response rate in heavily pretreated relapsed/refractory patients.

This treatment is specifically designed for patients who have undergone at least three prior therapies and have shown disease progression, highlighting its role in advanced stages of MM where other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. Martino, EA., Bruzzese, A., Labanca, C., et al.[2023]

In a phase 1 study involving 27 patients with relapsed and refractory multiple myeloma, CC-5013 was well tolerated at doses up to 25 mg/d, with no significant side effects like somnolence or neuropathy, although some patients experienced myelosuppression at higher doses.

CC-5013 demonstrated a significant efficacy, with 71% of patients showing at least a 25% reduction in paraprotein levels, indicating its potential as a treatment option for multiple myeloma, even in patients who had previously been treated with thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Richardson, PG., Schlossman, RL., Weller, E., et al.[2021]

Teclistamab is the first bispecific antibody approved for treating relapsed or refractory multiple myeloma, showing impressive efficacy in heavily pretreated patients, making it a promising option in this challenging area of treatment.

While teclistamab offers significant benefits, it also has notable adverse effects such as cytokine release syndrome, infections, and neurotoxicity, requiring careful management and precautions by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. Pan, D., Richter, J.[2023]

Cereblon is identified as a primary target for immunomodulatory drugs (IMiDs) in multiple myeloma (MM), and the IRF4 protein plays a crucial role in promoting MM cell survival by inhibiting pro-apoptotic factors.

Novel therapeutic agents, such as BET inhibitors and TAK1 inhibitors, show promise in overcoming IMiD resistance by targeting the IRF4/MYC signaling axis, potentially offering new treatment options for patients with relapsed or refractory MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanism of immunomodulatory drug resistance and novel therapeutic strategies in multiple myeloma. Zuo, X., Liu, D.[2022]

Teclistamab, a bispecific antibody targeting CD3 and BCMA, has received conditional approval in the EU and full approval in the US for treating adult patients with relapsed or refractory multiple myeloma after multiple prior therapies.

The approvals are based on its efficacy in patients who have undergone at least three to four previous treatments, including specific types of therapies, highlighting its role as a treatment option for difficult-to-treat cases of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. Kang, C.[2022]

Teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, has shown promising efficacy in treating relapsed/refractory multiple myeloma, with the recommended Phase II dose established at 1.5 mg/kg subcutaneously, which maintains drug levels above the effective concentration needed for maximum cytotoxicity.

The study utilized pharmacokinetic modeling to predict effective dosing ranges, confirming that doses of 0.27 mg/kg and 0.72 mg/kg intravenously, as well as 0.72 mg/kg subcutaneously, achieved serum concentrations that correlate with effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Girgis, S., Lin, SXW., Pillarisetti, K., et al.[2022]

Monoclonal antibodies like daratumumab and elotuzumab, especially when combined with other treatments, have shown high response rates and improved survival in patients with relapsed and refractory multiple myeloma, highlighting their efficacy in targeting specific plasma cell proteins.

CAR T cell therapy, particularly targeting B-cell maturation antigen (BCMA), has demonstrated dramatic remissions in patients with difficult-to-treat multiple myeloma, although it can lead to significant side effects like cytokine release syndrome and neurotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematologic Malignancies: Plasma Cell Disorders. Dhodapkar, MV., Borrello, I., Cohen, AD., et al.[2019]

Multiple myeloma (MM) is a challenging cancer affecting 15,000 new patients each year in the US, and current treatments are not curative.

Preliminary studies indicate that targeting the interactions between MM cells and their bone marrow environment, using treatments like thalidomide and proteasome inhibitors, may help overcome drug resistance and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic approaches for multiple myeloma. Hideshima, T., Richardson, P., Anderson, KC.[2019]

Transforming growth factor-beta (TGF-β) plays a crucial role in promoting multiple myeloma (MM) progression and drug resistance by suppressing anti-myeloma immune responses, highlighting the need to target this pathway for effective treatment.

Emerging immunotherapeutic strategies, such as CAR T cells and bispecific T cell engagers, show promise in blocking TGF-β signaling, which could enhance anti-myeloma immunity and overcome resistance to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting TGF-β signaling in the multiple myeloma microenvironment: Steering CARs and T cells in the right direction. Rana, PS., Soler, DC., Kort, J., et al.[2023]

Citations

1. simchatx.com simchatx.com/category/news/press-releases/

Press Releases Archives The multiple myeloma study is based on the hypothesis that ST-067 in combination with teclistamab will promote T-cell fitness and persistence, which could ...

2. researchgate.net researchgate.net/publication/386497118_Trial_in_Progress_ST-067_decoy-resistant_IL-18_with_Teclistamab_in_Multiple_Myeloma

ST-067 (decoy-resistant IL-18) with Teclistamab in Multiple ... If shown to have a favorable safety and efficacy profile in this and future studies, ST-067 has the potential to become a routine addition to ...

3. insight.jci.org insight.jci.org/articles/view/184545

Decoy-resistant IL-18 reshapes the tumor ... A “decoy-resistant” form of IL-18 (DR-18), that avoids sequestration by IL-18BP while maintaining its immunostimulatory potential, has recently been developed.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04787042

NCT04787042 | Phase 1a and Phase 2 Study for Safety, ... This is a multiphase, multicenter study, which includes a Phase 1a open-label, dose escalation monotherapy study of ST-067 given as an SC injection with or ...

5. globenewswire.com globenewswire.com/news-release/2025/10/21/3170153/0/en/Simcha-Therapeutics-Presents-Preclinical-Data-Demonstrating-Potential-for-Decoy-Resistant-IL-18-to-Enhance-Efficacy-of-Bi-specific-T-cell-Engagers.html

Simcha Therapeutics Presents Preclinical Data ... Its lead program, ST-067 is currently being evaluated in multiple clinical studies in solid tumors and hematologic malignancies. Simcha is ...

6. withpower.com withpower.com/trial/phase-1-neoplasms-plasma-cell-1-2025-a3290

ST-067 + Teclistamab for Multiple Myeloma Giving ST-067 in combination with teclistamab may be safe, tolerable and/or effective in treating patients with relapsed or refractory multiple myeloma. Show ...

7. cdek.pharmacy.purdue.edu cdek.pharmacy.purdue.edu/trial/NCT06588660/

Trial | NCT06588660 Giving ST-067 in combination with teclistamab may be safe, tolerable and/or effective in treating patients with relapsed or refractory multiple myeloma.

8. trialstat.com trialstat.com/2024/12/simcha-therapeutics-announces-the-opening-of-two-clinical-studies-exploring-st-067-in-hematological-indications/

Simcha Therapeutics Announces the Opening of Two ... Studies will assess ST-067 in acute myeloid leukemia or myelodysplastic syndrome and in multiple myeloma. Preclinical data to be presented ...