Using ST-067 and teclistamab to treat relapsed or refractory multiple myeloma

Phase 1b Study of ST-067 (Decoy-Resistant IL-18) With Teclistamab in Multiple Myeloma

This study is testing a new combination of two treatments, ST-067 and teclistamab, to see if they can help people with relapsed or refractory multiple myeloma feel better and improve their health.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Washington (other)
• Drugs / interventions: prednisone, teclistamab
• Locations: 1 site (Seattle, Washington)
• Trial ID: NCT06588660 on ClinicalTrials.gov

What this trial studies

This phase Ib trial evaluates the safety, side effects, and optimal dosage of ST-067 in combination with teclistamab for patients with relapsed or refractory multiple myeloma. ST-067 is an engineered variant of interleukin-18 designed to enhance the immune response against cancer cells, while teclistamab is a bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3 on T-cells. Participants will receive these treatments in a structured dosing schedule, with ongoing monitoring through blood samples and bone marrow biopsies. The study aims to determine the effectiveness and tolerability of this combination therapy.

Who should consider this trial

Good fit: Ideal candidates are adults with relapsed or refractory multiple myeloma who have undergone at least four prior lines of therapy.

Not a fit: Patients with early-stage multiple myeloma or those who have not yet received multiple lines of treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat multiple myeloma.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, suggesting potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Multiple myeloma, as defined by the presence of at least one International Myeloma Working Group (IMWG) MM-defining event
* Measurable disease as defined by IMWG criteria, requiring one or more of the following:

  * Serum M-protein ≥ 0.5 g/dL
  * Urine M-protein ≥ 200 mg/24h
  * Involved serum free light chain ratio ≥ 10 mg/dL with abnormal kappa/lambda ratio
  * Measurable plasmacytoma, defined as ≥ 1 lesion with cross-sectional diameter ≥ 2 centimeters)
  * Bone marrow plasma cell percentage ≥ 30%
* Eligibility to receive commercial tec per the Food and Drug Administration (FDA) package insert. This requires (1) at least 4 prior lines of therapy including a proteasome inhibitor (PI), immune modulatory imide drug (IMID), and CD38 monoclonal antibody (mAb); and (2) refractoriness, intolerance, or ineligibility (as deemed by the patient's treating physician) to other established therapies known to provide clinical benefit in MM

  * If the FDA package insert for tec is changed to allow for its use in earlier lines of therapy, the above-mentioned stipulations still apply until a protocol modification is approved
* Age ≥ 18 at study screening
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2
* Anticipated survival of \> 3 months
* Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min using the Modification of Diet in Renal Disease equation
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) both ≤ 3 x the lab's upper limit of normal (ULN)
* Total bilirubin ≤ 2 x ULN
* Platelets ≥ 25,000/μL at screening (no more than 1 transfusion in the 7-day period leading up to screening labs)
* Hemoglobin ≥ 7 g/dL at screening (no more than 1 transfusion in the 7-day period leading up to screening labs)
* Absolute neutrophil count (ANC) ≥ 1000 cells/mm\^3 at screening (no more than one administration of growth factor in the 7-day period leading up to screening labs)
* For patients of reproductive potential only: Willingness to use an effective contraceptive method before, during, and for at least 5 months after the last dose of study therapy
* Ability to understand and provide informed consent as well as willingness to comply with study requirements including visits and biopsies

Exclusion Criteria:

* History of prior BCMA-directed therapy in the past 12 months
* History of another primary malignancy that has not been in remission for at least 1 year

  * However, the following diagnoses are eligible for inclusion: non-melanoma skin cancer, localized prostate cancer, superficial bladder cancer, cervical carcinoma in situ, or any prior malignancy with an estimated \> 90% 1-year cure rate per sponsor-investigator
* Any condition requiring systemic treatment with corticosteroids (\> 10mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of study drug administration. This includes active cytokine release syndrome (CRS), active graft-versus-host disease, or autoimmune conditions

  * Inhaled or topical steroids are allowed, as are replacement corticosteroids for adrenal insufficiency
* Concurrent use of other anti-MM agents, including investigational drugs, within 7 days of study screening
* Known central nervous system (CNS) involvement of MM at time of study screening
* Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) at time of study screening
* Current pregnancy or breastfeeding, or planned pregnancy or breastfeeding within the next 12 months
* Corrected QT (QTc) interval (Bazett formula) ≥ 500 milliseconds on screening electrocardiogram (ECG)
* Uncontrolled or concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

Where this trial is running

Seattle, Washington

• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (RECRUITING)

Study contacts

• Principal investigator: Rahul Banerjee, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Rahul Banerjee, MD

Conditions: Recurrent Multiple Myeloma, Refractory Multiple Myeloma