A Study to Assess Adverse Events and Change in Disease Activity of Intravenously (IV) Infused ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Adult Participants With Relapsed/Refractory Multiple Myeloma

Study Overview
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Brief Summary
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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 ABBV-383 when co-administered with pomalidomide-dexamethasone (Pd), lenalidomide-dexamethasone (Rd), daratumumab-dexamethasone (Dd), or nirogacestat (Niro) in adult participants with relapsed/refractory (R/R) multiple myeloma (MM). Adverse events and change in disease activity will be assessed. ABBV-383 is an investigational drug being developed for the treatment of R/R MM. Study doctors put the participants in groups called treatment arms. ABBV-383 co-administered with Pd, Rd, Dd, or Niro 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 ABBV-383, followed by a dose expansion phase to confirm the dose. Approximately 270 adult participants with R/R MM will be enrolled in the study in approximately 45 sites worldwide. Participants will receive intravenous (IV) ABBV-383 co-administered with oral/IV Pd, oral/IV Rd, oral/IV/subcutaneous (SC) Dd, or oral/IV Niro 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.

Official Title
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A Dose Escalation and Expansion Study of ABBV-383 in Combination With Anti-Cancer Regimens for the Treatment of Patients With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: ABBV-383
* Drug: Dexamethasone
* Drug: Lenalidomide
* Drug: Pomalidomide
* Drug: Nirogacestat
* Drug: Daratumumab


Participation Criteria
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Eligibility Criteria
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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 outlined in the protocol. Must be naïve to treatment with ABBV-383 and must have never received BCMA-targeted therapy. Participants who have received targeted therapy against non-BCMA targets will not be excluded. Has received prior MM treatment in Arms A, B, C, and D. 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 drug 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. Known central nervous system involvement Multiple Myeloma (MM). Has any of the following conditions: Nonsecretory 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 drug 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. Known active infection of evidence of active hepatitis B, evidence of active hepatitis C, human immunodeficiency virus.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (ABBV-383 with Pomalidomide and Dexamethasone)<br>Participants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive ABBV-383 with Pomalidomide and Dexamethasone. | Drug: ABBV-383<br>* Intravenous (IV) Infusion<br>Drug: Dexamethasone<br>* Oral; Tablet or IV Infusion<br>Drug: Pomalidomide<br>* Oral; Capsule<br>|
| Experimental: Arm B (ABBV-383 with Lenalidomide and Dexamethasone)<br>Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Lenalidomide and Dexamethasone. | Drug: ABBV-383<br>* Intravenous (IV) Infusion<br>Drug: Dexamethasone<br>* Oral; Tablet or IV Infusion<br>Drug: Lenalidomide<br>* Oral; Capsule<br>|
| Experimental: Arm C (ABBV-383 with Daratumumab and Dexamethasone)<br>Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Daratumumab and Dexamethasone. | Drug: ABBV-383<br>* Intravenous (IV) Infusion<br>Drug: Dexamethasone<br>* Oral; Tablet or IV Infusion<br>Drug: Daratumumab<br>* Subcutaneous Injection (SC)<br>|
| Experimental: Arm D (ABBV-383 with Nirogacestat)<br>Participants with R/R MM who meet the criteria outline in the protocol will receive ABBV-383 with Nirogacestat. | Drug: ABBV-383<br>* Intravenous (IV) Infusion<br>Drug: Nirogacestat<br>* Oral; Tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLT) of ABBV-383 | DLT events as described in the protocol will be assessed. | Up to approximately 28 Days | 
| Number of Participants with Adverse Events (AEs) | 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. | Up to Approximately 3 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | 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. | Up to Approximately 3 Years | 
| Progression-Free Survival (PFS) | PFS is defined as the number of days from the date of first dose to the date of earliest disease progression or death. | Up to Approximately 3 Years | 
| Duration of Response (DOR) | 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. | Up to Approximately 3 Years | 
| Time-to-Progression (TTP) | TTP is defined as the number of days from the date of first dose to the date of earliest disease progression. | Up to Approximately 3 Years | 
| Percentage of Participants with Minimal Residual Disease Negativity (MRD) | MRD is defined as the percentage of participants with assessment of the minimal residual disease. | Up to Approximately 3 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lenalidomide, Relapsed/Refractory Multiple Myeloma, Pomalidomide, Dexamethasone, Daratumumab, Nirogacestat, ABBV-383, Cancer