A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody, in Subjects with Relapsed or Refractory Multiple Myeloma.
- Conditions
- Multiple Myeloma10018865
- Registration Number
- NL-OMON56207
- Lead Sponsor
- Janssen-Cilag
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 44
1. >=18 years of age. 2. Documented diagnosis of multiple myeloma according to
IMWG diagnostic criteria 3. Part 1 and Part 2: Measurable multiple myeloma that
is relapsed or refractory to established therapies with known clinical benefit
in relapsed/refractory multiple myeloma or be intolerant of those established
multiple myeloma therapies, and a candidate for teclistamab treatment in the
opinion of the treating physician. Prior lines of therapy must include a PI an
IMiD and an anti-CD38 monoclonal antibody in any order during the course of
treatment. Subjects who could not tolerate a PI, IMiD or an anti-CD38
monoclonal antibody are allowed. In Part 2 (dose expansion), in addition to
above criteria, multiple myeloma must be measurable per current IMWG published
guidelines by central lab assessment. If central lab assessment is not
available, relevant local measurement must exceed the minimum required level by
at least 25%. Part 3 Measurable disease Cohort A, Cohort C: Multiple myeloma
must be measurable by central laboratory assessment: • Serum monoclonal
paraprotein (M-protein) level >=1.0 g/dL or urine M-protein level >=200 mg/24
hours; or • Light chain multiple myeloma without measurable disease in the
serum or the urine: Serum immunoglobulin free light chain (FLC) >=10 mg/dL and
abnormal serum immunoglobulin kappa lambda FLC ratio. Prior treatment * Cohort
A: Subjects must have 1) received >=3 prior lines of therapy and 2) previously
received a PI, an IMiD, and an anti-CD38 monoclonal antibody. * Cohort C:
received >=3 prior lines of therapy that included a PI, an IMiD, an anti-CD38
monoclonal antibody, and an anti-BCMA treatment (with CAR-T cells or an ADC).
4. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
1, 5.Pretreatment clinical laboratory values meeting the incl criteria, 6.A
female subject of childbearing potential must have a negative pregnancy test at
screening and prior to the first dose of study drug using a highly sensitive
pregnancy test either serum (β human chorionic gonadotropin [β-hCG]) or urine.,
7. Female subjects of childbearing potential and fertile male subjects who are
sexually active must agree to use a highly effective method of contraception
(<1%/year failure rate). Contraception must begin from the time of signing the
ICF, continue during the study treatment, including during dose interruptions,
and through 6 months and 3 months after the last dose of study drug, for female
and male subjects, respectively. Contraception must be consistent with local
regulations regarding the use of birth control methods for subjects
participating in clinical trials. 8. Subject must sign an informed consent form
(ICF) indicating that he or she understands the purpose of and procedures
required for the study and is willing to participate in the study. Consent is
to be obtained prior to the initiation of any study-related tests or procedures
that are not part of standard-of-care for the subject*s disease., 9. Willing
and able to adhere to the prohibitions and restrictions specified in this
protocol.
1. Prior treatment with any BCMA targeted therapy, with the exception of Cohort
C in Part 3. 2.Prior antitumor therapy as follows, before the first dose of
study drug: * Targeted therapy, epigenetic therapy, or treatment with an
investigational drug or used an invasive investigational medical device within
21 days or at least 5 half-lives, whichever is less. * Monoclonal antibody
treatment for multiple myeloma within 21 days. * Cytotoxic therapy within 21
days. * Proteasome inhibitor therapy within 14 days. * Immunomodulatory agent
therapy within 7 days. * Gene modified adoptive cell therapy (eg, chimeric
antigen receptor modified T cells, natural killer [NK] cells) within 3 months.
* Radiotherapy within 14 days or focal radiation within 7 days, 3. Toxicities
from previous anticancer therapies that have not resolved to baseline levels or
to Grade 1 or less except for alopecia or peripheral neuropathy., 4. Received a
cumulative dose of corticosteroids equivalent to >=140 mg of prednisone within
the 14-day period before the first dose of study drug (does not include
pretreatment medication)., 5. Stem cell transplantation: * An allogeneic stem
cell transplant within 6 months. Subjects who received an allogeneic transplant
must be off all immunosuppresive medications for 6 weeks without signs of
graft-versus-host disease. * Received an autologous stem cell transplant <=12
weeks before the first dose of study drug, 6. Known active CNS involvement or
exhibits clinical signs of meningeal involvement of multiple myeloma., 7.
Plasma cell leukemia (>2.0 x 109/L plasma cells by standard differential),
Waldenstro*m*s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly,
endocrinopathy, monoclonal protein, and skin changes), or primary amyloid
light-chain amyloidosis., 8. Known to be seropositive for human
immunodeficiency virus or acquired immune deficiency syndrome, 9.Hepatitis B
infection or at risk for hepatitis B virus reactivation as defined according to
the American Society of Clinical Oncology guidelines. Eligibilty will be
determined by the investigator as described in the protocol. In the event the
infection status is unclear, quantitative levels are necessary to determine the
infection status. Active Hepatitis C infection as measured by positive
hepatitis C virus (HCV)-RNA testing, in subjects with positive anti-HCV
antibody or subjects with a history of HCV antibody positivity ., 10. Pulmonary
compromise requiring supplemental oxygen use to maintain adequate oxygenation.,
11. Known allergies, hypersensitivity, or intolerance to the study drug
(teclistamb) or its excipients (refer to Investigator*s Brochure), 12. Any
serious underlying medical condition, such as: * Evidence of serious active
viral, bacterial, or uncontrolled systemic fungal infection * Active autoimmune
disease or a documented history of autoimmune disease with the exception of
vitiligo, type I diabetes, and prior autoimmune thyroiditis that is currently
euthyroid based on clinical symptoms and laboratory testing * Psychiatric
conditions (eg, alcohol or drug abuse), dementia, or altered mental status *
Stroke, seizure e or transient ischemic attack within 6 months of signing ICF.
* Any other issue that would impair the ability of the subject to receive or
tolerate the planned treatment at
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method