A Phase 2 Study to Evaluate Safety and Efficacy of Teclistamab-, Talquetamab-, and JNJ-79635322-based Combination Regimens in Participants with Newly Diagnosed Transplant Eligible Multiple Myeloma OBJECTIVES: To evaluate the safety and tolerability of teclistamab-, talquetamab-, and JNJ-79635322-based combination regimens over the entire treatment phase for each arm, in participants with ND-TEMM To evaluate the efficacy of teclistamab- and talquetamab-based combination regimens as induction and post-transplant maintenance treatments; JNJ-79635322-based combinations as induction and as replacement for HDT+ASCT following induction; and teclistamab in combination with talquetamab
OVERALL DESIGN: 160 participants will be enrolled with 10 participants in Arm A, 20 participants in Arm A1, 20 participants in Arm B, 10 participants in Arms C and 10 in C2, 20 participants in Arm D, 10 participants in each Arm E, E1 and optionally F and F, and 20 participants in Arm G. Cohorts may be further expanded. Arms A, A1, B, D, E, E1, F, F1 will receive Induction therapy of 6 cycles (28-days each): Treatment: Tec-DRd (Arm A, A1), Tec-DVRd (Arm B), Tal-DRd (Arms E, E1), Tal-DVRd (Arms F, F1) followed by HDT and a single ASCT according to local SoC treatment. Thereafter a Maintenance Therapy of maximum 18 cycles with either Tec-D (Arms A, A1, B, E, F) or Tal-D (E1, F1) is performed. Arm D will receive 6 28-days cycles Tec-DVRd induction followed by 18 cycles Tec-Tal. Arm G will receive 6 28-day cycles of JNJ-79635322-DRd induction, followed by JNJ-79635322-D. No HDT ASCT will be performed in Arm D and Arm G. In Arm C and C2 participants will enter the study for maintenance treatment of 18 cycles with Tec-D (Arm C) or Tal-DR (Arm C2) , after induction, HDT and ASCT according to local SoC (outside of the study). Participants will receive maintenance treatment or following induction treatment (Arm D and G) for a maximum of 18 cycles or until confirmed progressive disease, death, intolerable toxicity, loss to follow-up, or consent withdrawal, whichever comes first. An optional end of treatment is possible for patients who have 12 months sustained MRD negativity. Periodic safety evaluations will be conducted to ensure that treatment is safe and tolerable. Upon treatment discontinuation, an EOT Visit will be conducted. Thereafter, the participant will continue in the Follow-up Phase until death, withdrawal of consent, loss to follow-up, or end of the study, whichever occurs first.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
160
Subcutaneous administration of Teclistamab
Subcutaneous administration of Daratumumab
administered i.v. or orally
Administration oral
Subcutaneous administration
Subcutaneous administration of Daratumumab
Subcutaneous administration
Charité University Medicin Berlin
Berlin, Germany
RECRUITINGClinic Chemnitz gGmbH
Chemnitz, Germany
RECRUITINGUniversity Clinic Technical University Dresden
Dresden, Germany
RECRUITINGUniversity Clinic Düsseldorf
Düsseldorf, Germany
RECRUITINGUniversity Clinic Freiburg
Freiburg im Breisgau, Germany
RECRUITINGHamburg University Clinic Eppendorf
Hamburg, Germany
RECRUITINGAsklepios Clinic Hamburg Altona
Hamburg, Germany
RECRUITINGUniversity Hospital Heidelberg
Heidelberg, Germany
RECRUITINGUniversity Clinic Schleswig-Holstein Campus Kiel
Kiel, Germany
RECRUITINGTechnical University Munich
Munich, Germany
RECRUITING...and 1 more locations
number of incidence and severity of adverse events [safety and tolerability]
Time frame: through study completion, up to 28 months
MRD negativity rate
MRD negativity rate measured by Flow Cytometry
Time frame: after 6 cycles (each cycle is 28 days) induction therapy (app.month 6), after High Dose Therapy (app. month 10), after 18 cycles (each cycle is 28 days) of maintenance therapy (app. month 28)
Response on therapy [efficacy]
Response on therapy according to IMWG: * Overall Response Rate (ORR) (at least a PR or better) * Complete Response (CR) or better * Very Good Partial Response (VGPR) or better * Duration of Response (DoR)
Time frame: after each cycle (each cycle is 28 days) induction ( app. at month 1,2,...,6), after High Dose therapy (app. month 10), after each cycle (each cycle is 28 days) of maintenance (app. at month 11,12, ...28), during FU every 3 months (app. up to 3-4 years)
Progression Free Survival [efficacy]
Time frame: From randomization to the date of disease progression to death (app. up to 3-4 years)
Serum concentration of teclistamab, talquetamab and daratumumab [pharmacokinetics]
Time frame: through study completion, up to 28 months
Presence of ADAs to teclistamab, talquetamab and daratumumab [immunogenicity]
Time frame: through study completion, up to 28 months
Stem cell yield
feasibility of successful transplantation
Time frame: after High Dose Therapy (after app. 10 months)
days to engraftment
feasibility of successful transplantation
Time frame: after High Dose Therapy (after app. 10 months)
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