An Open label Study of Teclistamab in Subjects with Relapsed and Refractory Multiple Myeloma
- Conditions
- Relapsed or Refractory Multiple MyelomaMedDRA version: 20.0Level: HLGTClassification code 10005330Term: Blood and lymphatic system disorders congenitalSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002122-36-GB
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 228
1. =18 years of age.
2. Documented diagnosis of MM according to IMWG diagnostic criteria.
3. Part 1 and Part 2
Measurable MM that is relapsed or refractory to established therapies with known clinical benefit in relapsed/refractory MM or be intolerant of those established MM 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 anti-CD38 monoclonal antibody are allowed. In Part 2 (dose expansion), in addition to above criteria, MM must be measurable per current IMWG published guidelines by central lab assessment. If central lab assessment is not available, relevant local lab measurement must exceed the minimum required level by at least 25%.
Part 3
Measurable disease
Cohort A, B,C: MM must be measurable by central lab assessment:
- Serum monoclonal paraprotein (M-protein) level =1.0 g/dL or urine M-protein level =200 mg/24 hours; or
- Light chain MM 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. If central lab assessments are not available, relevant local lab measurements must exceed the min required level by at least 25%.
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 B: received =4 prior lines of therapy and whose disease is penta-drug refractory to an anti-CD38 monoclonal antibody, =2 PIs, =2 IMiDs (refractory multiple myeloma as defines by IMWG consensus criteria).
- 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 lab values meeting the predefined criteria during the Screening Phase (see table on pg 107-108 of protocol)
6. Women 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 (ß human chorionic gonadotropin [ß-hCG]) or urine.
7. Women of childbearing potential and fertile men who are sexually active must agree to use a highly effective method of contraception (<1% / year failure rate) from the time of signing the ICF during the study and for 90 days after the last dose of study drug. Contraception must be consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials.
When a woman is of childbearing potential the following are required:
- Subject must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly). Examples of highly effective contraceptives include:
– user-independent methods: 1) implantable progestogen-only hormone contraception associated with inhibition of ovulation; 2) intrauterine device;
intrauterine hormone-releasing system; 3) vasectomized partner;
– user-dependent methods: 1) combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation: oral orintravaginal or transdermal; 2) progestogen-only hormone contraception associated with in
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 immunosuppressive 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 10 to the 9th/L plasma cells by standard differential), Waldenström’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
10. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation.
11. Known allergies, hypersensitivity, or intolerance to the study drug (teclistamab) or its excipients.
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 or seizure 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 the investigational site, to understand informed consent or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
Any potential subject who meets any of the following criteria will be excluded from participating in Part 3:
16. The following cardiac conditions:
•New York Heart Association stage III or IV congestive heart failure
•Myocardial infarction or coronary artery bypass graft (CABG) =6 months prior to enrollment
•History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
•History of severe non-ischemic cardio
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method