Tab Title Description
Describes the nature of a clinical study. Types include:
- Observational study — observes people and measures outcomes without affecting results.
- Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
- Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
NCT ID: NCT03933735
Sponsor Protocol Number: TNB383B.0001
About this study
The purpose of this study is to evaluate the safety, clinical pharmacology and clinical activity of TNB-383B, a T-cell engaging bispecific antibody, in subjects with relapsed or refractory MM who have received at least 3 prior lines of therapy. The study consists of 2 portions, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Arm A will evaluate the safety, tolerability, PK and PD profiles of escalating doses of single-agent TNB-383B ranging from 25 micrograms to 40 milligrams per dose, administered once every 3 weeks (Q3W), in approximately 24 subjects. Once the maximum tolerated dose (MTD) or recommended phase 2 dose, (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the MTD/RP2D dose of TNB 383B monotherapy in approximately 48 subjects.
Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
- Subject must be ≥ 18 years of age.
- Three or more prior lines of therapy with exposure to a PI, an IMiD, and an anti-CD38 antibody (e.g., daratumumab). In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in MM.
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
- Subject is capable of understanding and complying with parameters as outlined in the protocol and able to sign informed consent.
- Subject must have adequate bone marrow function, defined as:
- absolute neutrophil count (ANC) ≥ 1000/mm^3;
- platelets ≥ 50,000/mm^3;
- hemoglobin ≥ 8.0 g/dL;
- Transfusion and / or growth factor support is permitted prior to assessment, but neutrophils, platelets, and hemoglobin must be stable for at least 72 hours after transfusion and / or growth factor administration prior to Screening for the subject to be eligible.
- Subject must have an eGFR ≥ 30 mL/min as estimated by the MDRD formula.
- Subject must have total bilirubin ≤ 1.5 × upper limit of normal (ULN; except if the subject has a known diagnosis of Gilbert’s syndrome, in which case bilirubin must be < 3 x ULN).
- Serum calcium (corrected for albumin) at or below the ULN range (subject may enroll in the setting of hypercalcemia at Screening IF hypercalcemia resolves with standard treatment by Cycle 1 Day 1) prior to study therapy initiation.
- Measurable Disease: Subject has a diagnosis of MM and documented prior treatment with a PI, an IMiD, and an anti-CD38 mAb (ie, daratumumab) as part of 3 or more lines of therapy. In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in MM. There is no maximum number of prior regimens and prior bone marrow transplant is acceptable if subject is > 12 weeks (autologous) or > 1 year (allogeneic) status-post transplantation.
- Measurable disease is defined as at least 1 of the following:
- Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L);
- Urine M-protein ≥ 200 mg / 24h;
- Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dl (≥ 100 mg/L) and an abnormal serum FLC ratio (< 0.26 or > 1.65).
- Subject has confirmed evidence of relapse / progression from the immediately prior MM therapy, or subject is relapsed / refractory to the immediately prior MM therapy. (‘Refractory’ is defined as subjects with either progressive disease or best response of stable disease to the last therapy; ‘Relapsed / refractory’ is defined as subjects with a history of minimal response [MR] or better response to prior therapy, now with disease progression within 60 days of the last therapy. ‘Relapse’ is defined as previously treated myeloma that progresses and requires initiation of salvage therapy, without meeting IMWG uniform response criteria for relapsed / refractory).
- Subject has adequate archival tumor bone marrow tissue if available or consents to a fresh pre- treatment bone marrow tumor biopsy.
- Subject has been diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of basal cell or squamous cell carcinoma of the skin, in situ malignancy, low-risk prostate carcinoma after curative therapy, or complete resection / curative therapy of an advanced malignancy.
- Subject has a history of central nervous system (CNS) involvement by their myeloma.
- Subject has a history of Grade ≥ 3 peripheral neuropathy.
- Subject has a history of plasma cell leukemia, POEMS syndrome, or amyloidosis.
- Subject has received another investigational drug within 21 days of enrollment.
- Subject has ever received BCMA-targeted therapy. Subjects who have received targeted therapy against non-BCMA targets will not be excluded.
- Subject has received a peripheral autologous stem cell transplant within 12 weeks or an allogeneic stem cell transplant within 1 year of the first dose of study drug treatment.
- Subject has any medical or psychiatric condition which in the opinion of the investigator or Study Medical Monitor places the subject at an unacceptably high risk for toxicities, could interfere with successful or safe delivery of therapy, or could interfere with evaluation of the investigational product or interpretation of subject safety or study results. Examples include history of significant mucosal / internal bleeding, major psychiatric illness, drug abuse (including active alcoholism), or known allergy or hypersensitivity to components of the study drug formulation.
- Subject has received any therapy to treat cancer (including radiation, chemotherapy, biologics, cellular therapies and / or steroids at doses > 20 mg dexamethasone or equivalent) or undergone a major surgical procedure within 21 days, or within 5 half-lives of an anti-cancer drug, prior to the first dose of study treatment, whichever is shorter.
- Subject has known infection Grade ≥ 2 requiring anti-infective treatment. Upon completion of antibiotics and resolution to Grade ≤ 1, the subject is considered eligible for the study from an infection standpoint.
- Confirmed positive test results for human immunodeficiency virus (HIV), or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who have a history of HBV or HCV who have documented cures (HBV: hepatitis B surface antigen [HBsAg] negative; HCV: undetectable HCV RNA 24 weeks after the end of treatment) may be enrolled.
- Major cardiac abnormalities such as but not limited to the following: uncontrolled angina or unstable life-threatening arrhythmias, history of myocardial infarction ≤ 12 weeks before Screening, Class ≥ 3 New York Heart Association congestive heart failure, severe cardiac insufficiency, or persistent QTc prolongation (> 480 msec, QTc Fridericia).
- If female, subject must not be pregnant or breastfeeding and be either postmenopausal (for at least 12 consecutive months), OR permanently surgically sterile OR for women of childbearing potential practicing at least 1 protocol specified method of female birth control AND 1 protocol specified method of male birth control (vasectomy or condoms), starting at Screening through at least6 months after the last dose of study drug.
- Subject has unresolved AEs ≥ Grade 2 (NCI CTCAE v5.0) from prior anticancer therapy except for:
- Peripheral neuropathy (peripheral neuropathy ≥ Grade 3 will be excluded);
- Anemia or thrombocytopenia (the latter cytopenias must be Grade 4 to trigger exclusion, Grade 3 with symptoms or bleeding, respectively, or return within 72 hours despite transfusion support);
- Subjects with irreversible toxicity not reasonably expected to be exacerbated by any of the investigational products may be included (e.g., hearing loss) after consultation with the Study Medical Monitor.
Eligibility last updated 2/11/22. Questions regarding updates should be directed to the study team contact.
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