Relapsed/Refractory Multiple Myeloma
Conditions
Keywords
Relapsed/Refractory Multiple Myeloma, Pomalidomide, Dexamethasone, Lenalidomide, Daratumumab, Nirogacestat, Etentamig, ABBV-383, Cancer
Brief summary
Multiple myeloma (MM) is a plasma cell disease characterized by the growth of clonal plasma cells in the bone marrow. The purpose of this study is to assess the safety and toxicity of etentamig (ABBV-383) when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), or daratumumab-dexamethasone (Dd), in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed. Etentamig is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. Etentamig co-administered with Pd, Rd, or Dd, will be explored. Each treatment arm receives a different treatment combination depending on stage of the study and eligibility. This study will include a dose escalation phase to determine the best dose of etentamig, followed by a dose expansion phase to confirm the dose. Approximately 320 adult participants with R/R MM will be enrolled in the study in approximately 48 sites worldwide. Participants will receive intravenous (IV) etentamig co-administered with oral/IV Pd, oral/IV Rd, or oral/IV/subcutaneous (SC) Dd in 28-day cycles. There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.
Interventions
DRUGEtentamig
Intravenous (IV) Infusion
DRUGDexamethasone
Oral; Tablet or IV Infusion
DRUGLenalidomide
Oral; Capsule
DRUGPomalidomide
Oral; Capsule
DRUGDaratumumab
Subcutaneous Injection (SC)
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance of \<= 2. * Must have confirmed diagnosis of Relapsed/Refractory (R/R) Multiple Myeloma (MM) with documented evidence of progression during or after the participant's last treatment regimen based on the investigator's determination of the International Myeloma Working Group (IMWG) criteria. * Must have measurable disease as determined by central lab as outlined in the protocol. * Must be naïve to treatment with Etentamig. * Must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded. * Arms A, B and C: Participant has received at least 3 prior lines of MM treatment. * Arm E: Participant has received 1-3 prior lines of MM treatment.
Exclusion criteria
* Received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study treatment. * Unresolved adverse event (AE)s \>= Grade 2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) from prior anticancer therapy. * Has any of the following conditions: * Nonsecretory Multiple Myeloma (MM). * Active Plasma cell leukemia i.e., either 20% of peripheral white blood cells or \> 2.0 × 10\^9L circulating plasma cells by standard differential. * Waldenstrom's macroglobulinemia. * Light chain amyloidosis. * Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes (POEMS) syndrome. * Major surgery within 4 weeks prior to first dose or planned study participation. * Acute infections within 14 days prior to first dose of study requiring therapy (antibiotic, antifungal or antiviral). * Uncontrolled diabetes or hypertension within 14 days prior to first dose. * Peripheral neuropathy \>= Grade 3 or \>= Grade 2 with pain within 2 weeks prior to first dose.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Dose Limiting Toxicities (DLT) of Etentamig | Up to approximately 28 Days | DLT events as described in the protocol will be assessed. |
| Number of Participants with Adverse Events (AEs) | Up to Approximately 3 Years | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | Up to Approximately 3 Years | ORR is defined as partial response (PR) + very good partial response (VGPR) + complete remission (CR) + stringent complete response (sCR); proportion of participants who achieved a PR or better. |
| Progression-Free Survival (PFS) | Up to Approximately 3 Years | PFS is defined as the number of days from the date of first dose to the date of earliest disease progression or death. |
| Duration of Response (DOR) | Up to Approximately 3 Years | DOR will be defined as the number of days from the date of first response (sCR, CR, VGPR, or PR) to the earliest recurrence, progressive disease, or death, whatever occurs first. |
| Time-to-Progression (TTP) | Up to Approximately 3 Years | TTP is defined as the number of days from the date of first dose to the date of earliest disease progression. |
| Percentage of Participants with Minimal Residual Diseas (MRD) Negativity by Next-Generation Sequencing (NGS) | Up to Approximately 3 Years | MRD negative status (threshold as assessed by NGS Adaptive Clonoseq) with \>= CR (per International Myeloma Working Group \[IMWG\] response criteria) prior to the initiation of new myeloma therapy. |
Countries
Australia, Germany, Italy, Japan, Poland, Spain, United States
Contacts
STUDY_DIRECTORABBVIE INC.
AbbVie
Outcome results
None listed