ST-067 and Teclistamab for the Treatment of Relapsed or Refractory Multiple Myeloma

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 or therapies, including investigational drugs, within 7 days of cycle 1 day 1. * Corticosteroids for other purposes, including for pain control, are allowed during the screening period but must also be stopped >= 7 days prior to cycle 1 day 1. * Similarly, focal radiation therapy for palliative purposes is permitted during the screening period but must also be completed >= 7 days prior to cycle 1 day 1
• 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