None listed
Conditions
Interventions
Drug : 1. Teclistamab (Each cycle = 28 days)
1) Cycle 1
Two step-up doses (0.06 mg/kg and 0.3 mg/kg, SC) on Days 2 and 4, followed by 1.5 mg/kg SC on Days 8 and 15.
2) Cycles 2–24
3 mg/kg SC on Day 1
Sponsors
Asan Medical Center
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects with newly diagnosed MM or suspected MM, as defined by the International Myeloma Working Group (IMWG) criteria. Bone marrow plasma cells =10% must be confirmed prior to the first administration of the investigational medicinal product (IMP). (See Appendix IA) Age = 19 years at the time of obtaining informed consent. Eastern Cooperative Oncology Group (ECOG) performance status 0–2. Not considered a candidate for high-dose chemotherapy with ASCT, due to one of the following: Ineligibility related to age (=70 years at the time of transplant), or Deferral of high-dose chemotherapy with ASCT as part of initial therapy, or Patient preference or refusal regarding autologous stem cell transplantation (for subjects =65 years). No prior therapy for multiple myeloma, except for short-term corticosteroids (up to 40 mg dexamethasone per day or equivalent for a maximum of 4 days, not exceeding a total of 160 mg dexamethasone or equivalent). Measurable disease, fulfilling at least one of the following criteria (at screening or prior to induction therapy): Serum monoclonal (M) protein = 1.0 g/dL Urine M-protein = 200 mg/24 hours Serum free light chain = 10 mg/dL with an abnormal kappa/lambda ratio Availability of a FISH report indicating the presence or absence of high-risk cytogenetic abnormalities [del(17p), t(4;14), t(14;16), 1q gain/amplification, 1p deletion]. Available results for albumin, beta-2 microglobulin, and lactate dehydrogenase (LDH) at screening or prior to initiation of anticancer therapy. Adequate laboratory values within 28 days prior to initiation of study treatment: Absolute neutrophil count (ANC) = 1,000/mm³, independent of growth factor support Hemoglobin > 7.5 g/dL Platelet count = 75,000/mm³, independent of transfusion support Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3 × upper limit of normal (ULN) Total bilirubin < 1.5 mg/dL (unless due to Gilbert’s syndrome or non-hepatic causes) Creatinine clearance = 30 mL/min (calculated using the Cockcroft–Gault formula) Voluntary provision of informed consent. Women of childbearing potential (WOCBP) must agree to use effective contraception during the study and must have a negative urine (or serum) pregnancy test =7 days prior to first dosing. Effective contraception must be continued for 5 months after the last dose of teclistamab and 3 months after the last dose of daratumumab. For subjects receiving lenalidomide, two effective contraceptive methods—one of which must be a highly effective method—must be used from 4 weeks prior to treatment until 4 weeks after treatment, with two negative pregnancy tests required prior to initiation (10–14 days before and within 24 hours of first dosing). Male subjects who are not sterile must use highly effective contraception during the study and for =90 days after the last dose of study treatment, and must not donate sperm. (A “sterile” male is defined as one with documented azoospermia confirmed by prior semen analysis.) Highly effective methods of contraception include: Intrauterine device (IUD) Bilateral tubal occlusion (surgical sterilization preventing fertilization) Vasectomy of the female partner’s male partner (confirmed successful upon medical assessment) Hormonal contraception that inhibits ovulation: combined estrogen/progestin oral contraceptives, progestin-only pills, transdermal patch, vaginal ring, or subcutaneous injectable contraceptives Sexual abstinence (only if refraining from heterosexual int
Exclusion criteria
Exclusion criteria: Diagnosis of amyloidosis, POEMS syndrome, Waldenström macroglobulinemia, or plasma cell leukemia. Major surgery, radiotherapy, or clinically significant infection requiring treatment within 14 days prior to initiation of study therapy. History of another primary malignancy except for: Subjects who have remained disease-free for =3 years, or The following non-invasive malignancies: basal cell carcinoma of the skin, squamous cell carcinoma in situ (Stage 0), cervical carcinoma in situ, ductal carcinoma in situ (DCIS) of the breast, early-stage gastric cancer, and prostate cancer that is T1a or T1b or otherwise considered cured. Prior history of solid organ transplantation or other causes of severe immunodeficiency. History of severe allergic reaction or anaphylaxis to humanized or murine monoclonal antibodies, or known hypersensitivity or allergy to murine-derived products. Unstable angina or myocardial infarction within 4 months prior to enrollment, NYHA Class III or IV heart failure, history of severe coronary artery disease, uncontrolled severe ventricular arrhythmias, sick sinus syndrome, or ECG evidence of acute ischemia or Grade 3 conduction abnormalities. (Subjects with functioning pacemakers are exempt.) Any serious medical condition or clinical laboratory abnormality that, in the opinion of the investigator or medical monitor, could compromise patient safety, interfere with study participation, or impact data interpretation. Cerebrovascular disease presenting as stroke or TIA within 12 months prior to study treatment initiation. Known HIV infection. (HIV-positive subjects with persistently undetectable viral load may be enrolled.) Positive serology for hepatitis B, defined as HBsAg positivity. Subjects with resolved infection (HBsAg-negative with anti-HBc positivity, regardless of anti-HBs status) must undergo HBV DNA RT-PCR screening. Subjects with positive HBV DNA are excluded. Subjects with serology indicating prior vaccination (isolated anti-HBs positivity with known vaccination history) do not require HBV DNA testing. For subjects with positive hepatitis C antibody, HCV RNA must be negative prior to enrollment. Subjects with detectable HCV RNA are excluded. Clinically significant peripheral neuropathy (Grade 3–4, or Grade 2 with pain) within 28 days prior to enrollment. Pregnant or breastfeeding women. Breastfeeding women must agree to discontinue breastfeeding while receiving lenalidomide. Inability or unwillingness to comply with antithrombotic prophylaxis (e.g., aspirin, enoxaparin, low-molecular-weight heparin). Alcohol or substance abuse disorder. Uncontrolled active infections (e.g., tuberculosis, hepatitis B) at screening. Inability to swallow medications or conditions significantly affecting gastrointestinal absorption, including malabsorption syndrome, diseases interfering with GI function, prior gastrectomy or significant small bowel resection, symptomatic inflammatory bowel disease, ulcerative colitis, or partial/complete bowel obstruction. Receipt of systemic corticosteroids with a cumulative dose equivalent to =20 mg of dexamethasone during the screening period. COPD with FEV1 < 50% predicted. FEV1 testing is required only for subjects with suspected COPD. Moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification. Subjects with controlled intermittent asthma or controlled mild persistent asthma may participate.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Sustained MRD negativity for = 6 months (at a threshold of 10?5 as determined by NGF);safety profile;Dose-limiting toxicity | — |
Secondary
| Measure | Time frame |
|---|---|
| Sustained MRD negativity for = 12 months (at a threshold of 10?5).;Proportion of imaging-negative + MRD-negative patients. Proportion of patients achieving stringent complete response (sCR) or better. Proportion of patients achieving complete response (CR) or better. Proportion of patients achieving very good partial response (VGPR) or better. Overall response rate (ORR). Progression-free survival (PFS). Overall survival (OS).;Patient-reported outcome measures (EORTC QLQ-C30).;Incidence of grade 3 or 4 infection;Evaluation of the Prognostic Value of Mass Spectrometry;Evaluation of the association between the composition and functional profiles of immune cell subsets in bone marrow and peripheral blood before and during treatment, the tumor microenvironment characterized by spatial transcriptomics, and clinical efficacy outcomes. | — |
Countries
Korea, Republic of
Contacts
Public ContactNa Eun Lee
Asan Medical Center
Outcome results
None listed