Multiple Myeloma MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. =18 years of age. 2. Documented multiple myeloma as defined by the criteria below: a. Multiple myeloma diagnosis according to the IMWG diagnostic criteria b. Measurable disease at screening as defined by any of the following: 1) Serum M-protein level =0.5 g/dL (central laboratory); or 2) Urine M-protein level =200 mg/24 hours (central laboratory); or 3) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum immunoglobulin free light chain =10 mg/dL (central laboratory), and abnormal serum immunoglobulin kappa lambda free light chain ratio (0.22 to 1.52 [central laboratory]). 3. Relapsed or refractory disease as defined below: a. Relapsed disease is defined as an initial response to prior treatment, followed by confirmed progressive disease by IMWG criteria >60 days after cessation of treatment. b. Refractory disease is defined as 300 cells/mm3 at screening - No acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 6 months of screening - Receiving highly active antiretroviral therapy (HAART). Any changes in HAART due to resistance/progression should occur at least 3 months prior to screening. A change in HAART due to toxicity is allowed up to 4 weeks prior to screening. 9. A female participant of childbearing potential must have a negative highly sensitive urine or serum (ß human chorionic gonadotropin [ß hCG]) pregnancy test at screening, within 24 hours prior to the start of study treatment, and must agree to further urine or serum pregnancy tests during the study and within 100 days after receiving the last dose of study treatment. 10. A female participant must be: a. Not of childbearing potential, or b. Of childbearing potential and 1) Practicing true abstinence; or 2) Have a sole partner who is bilaterally vasectomized; or 3) Practicing 2 effective methods of contraception (at least 1 highly-effective, method of contraception). For participants who are of childbearing potential, see protocol Section 6.12.3 for details regarding concomitant use of estrogen containing products and pomalidomide 11. A female participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for at least 100 days after the last dose of study treatment. Female participants should consider preservation of eggs
Exclusion criteria
Exclusion criteria: 1. Contraindications or life-threatening allergies, hypersensitivity, or intolerance to study drug excipients (refer to the talquetamab IB and appropriate package inserts). 2. Disease is considered refractory to an anti-CD38 monoclonal antibody as defined per IMWG consensus guidelines (progression during treatment or within 60 days of completing therapy with an anti-CD38 monoclonal antibody). 3. Prior or concurrent exposure to any of the following, in the specified time frame prior to randomization: a. GPRC5D-directed therapy b. Received prior pomalidomide therapy c. T cell redirection therapy (for example, antibody therapy or BiTE’s) within 3 months d. Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, NK cells) within 3 months e. Targeted therapy, epigenetic therapy, or treatment with an investigational drug or an invasive investigational medical device within 21 days or =5 half-lives, whichever is less f. Investigational vaccine other than SARS CoV-2 vaccine approved/ in use under emergency approval within 4 weeks g. Live, attenuated vaccine within 4 weeks h. Monoclonal antibody therapy within 21 days i. Cytotoxic therapy within 21 days j. PI therapy within 14 days k. IMiD agent therapy within 14 days l. Radiotherapy within 14 days or focal radiation within 7 days 4. Received either of the following: a. An allogeneic SCT within 6 months before the first dose of study treatment. Participants who received an allogeneic transplant must be off all immunosuppressive medications during the 6 weeks before the start of study treatment administration without signs of graft versus host disease b. An autologous SCT within 12 weeks before the start of study treatment administration. 5. A maximum cumulative dose of corticosteroids to =140 mg of prednisone or equivalent within 14-day period before the first dose of study drug 6. Known active CNS involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain MRI and lumbar cytology are required. 7. Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis. 8. Myelodysplastic syndrome or active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than relapsed/refractory multiple myeloma. The only allowed exceptions are: a. Non-muscle invasive bladder cancer (solitary Ta- Papillary Urothelial Neoplasm of Low Malignant Potential or low grade, 6 months prior to full study screening and considered to have a very low risk of recurrence e. History of localized prostate cancer and receiving androgen deprivation therapy and considered to have a very low risk of recurrence f. Breast cancer: adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents an
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of Tal-DP and Tal-D, respectively, with DPd;Secondary Objective: 1. To further compare the efficacy of Tal-DP and Tal- D, respectively, with DPd 2. To assess the safety profile of Tal-DP and Tal-D 3. To characterize the PK of talquetamab 4. To assess the immunogenicity of talquetamab and daratumumab 5. To assess changes in patient-reported outcomes (PROs) with Tal-DP, DPd, and Tal-D;Primary end point(s): Progression Free Survival;Timepoint(s) of evaluation of this end point: Subjects will have disease evaluation performed by the central laboratory Day 1 of every cycle until disease progression. This endpoint will be evaluated at interim analysis and primary analysis. The projected time frame is up to 4 years. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. -Overall response (PR or better) - VGPR or better - CR or better - Overall MRD negativity status - OS - PFS2 - TTNT 2. Incidence and severity of AEs 3. PK parameters using population PK approach 4. Presence of ADAs to talquetamab and daratumumab 5. -Time to worsening in symptoms, functioning, and overall HRQoL - Change from baseline in symptoms, functioning, and overall HRQoL;Timepoint(s) of evaluation of this end point: These endpoints will be evaluated at interim analysis and primary analysis. | — |
Countries
Belgium, Brazil, China, Czechia, Czech Republic, France, Germany, Greece, Israel, Italy, Japan, Korea, Republic of, Netherlands, Poland, Spain, Taiwan, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed