A Dose Escalation Study of Talquetamab in Participants with Relapsed or 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
- EUCTR2017-002400-26-NL
- Lead Sponsor
- Janssen-Cilag International NV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 718
1. =18 years of age.
2. Criterion modified per Amendment 11
2.1. Documented initial diagnosis of multiple myeloma according to IMWG diagnostic a criteria
3. Criterion modified per Amendment 1, 11, 13, 16
3.4. Part 1: Subjects with measurable multiple myeloma who have progressed on, or could not tolerate, all available established therapies.
Part 2: Subjects with multiple myeloma measurable by central laboratory assessment who have progressed on, or could not tolerate, all available established therapies:
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 FLC =10 mg/dL and abnormal serum immunoglobulin kappa lambda FLC ratio
If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%.
Part 3: Measurable disease
Cohort A, Cohort B and 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.
If central laboratory assessments are not available, relevant local laboratory measurements must exceed the minimum required level by at least 25%.
Prior treatment
- Cohort A and Cohort C: have previously received =3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have not been exposed to T cell redirection therapies such as CAR-T or bispecific antibodies.
- Cohort B: have previously received =3 prior lines of therapy that included at least one PI, one IMiD, and an anti-CD38 monoclonal antibody, and have been exposed to T cell redirection therapies such as
CAR-T or bispecific antibodies.
Cohorts A, B and C:
Undergone at least 1 complete cycle of treatment for each line of therapy, unless progressive disease was the best response to the line of therapy.
Subject must have documented evidence of progressive disease based on investigator's determination of response by the IMWG 2016 criteria on or within 12 months of their last line of therapy. Criteria for progressive disease on or within 12 months of therapy does not apply to patients with CAR-T as last line of therapy. Also, subjects with documented evidence of progressive disease within the previous 6 months and who are refractory or non-responsive to their most recent line of therapy afterwards are eligible.
4. Criterion modified per Amendment 11, 12
4.2. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 for Parts 1 and 2 and 0-2 for Part 3 of the study..
5. Criterion modified per Amendment 1, 9, 11, 12
5.4. Pretreatment clinical laboratory values meeting the predefined criteria during the Screening Phase
6. Criterion modified per Amendment 10, 11
6.2 Women of childbearing potential (WOCBP) 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.
. a woman is considered of childbearing potential (WOCBP) ie, fertile, following menarche and until becoming postmenopausal unless permanently sterile. Permanent sterilization method
1. Criterion modified per Amendment 11 and 13
1.2. Prior Grade 3 or higher CRS (Per Lee Criteria 2014) related to any T cell redirection (eg, CD-3 redirection technology or CAR-T cell therapy) or any prior GPRC5D targeting therapy
2. Criterion modified per Amendment 10, 11, 13.
2.3 Prior antitumor therapy as follows, prior to the first dose of study drug:
. Gene modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells [CAR-T], natural killer [NK] cells) within 3 months.
. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or 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.
. Radiotherapy within 14 days. However, if palliative focal radiation is used, the subject is eligible irrespective of the end date of radiotherapy.
Part 3 only:
. Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time.
. Cohort B: T cell redirection therapy within 3 months
3. Criterion modified per Amendment 11, 16
3.2. Participants who received or plan to receive any live, attenuated vaccine within 4 weeks prior to the first dose, during treatment, or within 4 weeks of the last dose of talquetamab. Non-live or non-replicating vaccines approved or authorized for emergency use (eg, COVID-19) by local health authorities are allowed.
4. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
5. Criterion modified per Amendment 11.
5.1. 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).
6. Received either of the following:
. An allogenic stem cell transplant within 6 months before first dose of study drug. Subjects who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft versus host disease (GVHD).
. An autologous stem cell transplant =12 weeks before first dose of study drug
7. Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required.
8. Criterion modified per Amendment 6
8.1. Criterion modified per Amendment 11
8.2. 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 [M-protein], and skin changes), or primary amyloid light chain amyloidosis.
9. Known to be seropositive for human immunodeficiency virus or acquired immune deficiency syndrome.
10. Criterion modified per Amendment 11
10.1. Hepatitis B infection as defined according to the American Society of Clinical Oncology guidelines. 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 HCV-RNA testing. Subjects with a history of Hepatitis C virus antibody positivity must undergo HCV-RNA testing.
11. Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxyge
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