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

Phase 1
Recruiting
Conditions
Relapsed/Refractory Multiple Myeloma
Interventions
Registration Number
NCT05259839
Lead Sponsor
TeneoOne Inc.
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
320
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone)DexamethasoneParticipants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.
Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone)PomalidomideParticipants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.
Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone)LenalidomideParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.
Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone)EtentamigParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.
Part 1: Arm B (Etentamig with Lenalidomide and Dexamethasone)DexamethasoneParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Lenalidomide and Dexamethasone.
Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone)DexamethasoneParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.
Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone)DaratumumabParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.
Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone)DexamethasoneParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.
Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone)PomalidomideParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.
Part 2: Arm E (Etentamig with Pomalidomide and Dexamethasone)EtentamigParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone, after 1-3 prior lines of therapy.
Part 1: Arm A (Etentamig with Pomalidomide and Dexamethasone)EtentamigParticipants with relapsed or refractory (R/R) multiple myeloma (MM) who meet the criteria outline in the protocol will receive etentamig with Pomalidomide and Dexamethasone.
Part 1: Arm C (Etentamig with Daratumumab and Dexamethasone)EtentamigParticipants with R/R MM who meet the criteria outline in the protocol will receive etentamig with Daratumumab and Dexamethasone.
Primary Outcome Measures
NameTimeMethod
Number of Participants with Dose Limiting Toxicities (DLT) of EtentamigUp 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 Outcome Measures
NameTimeMethod
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.

Trial Locations

Locations (49)

Hospital Universitario Virgen del Rocio /ID# 242974

🇪🇸

Sevilla, Spain

St George Hospital /ID# 243740

🇦🇺

Kogarah, New South Wales, Australia

University of Arkansas for Medical Sciences /ID# 243096

🇺🇸

Little Rock, Arkansas, United States

Sylvester Comprehensive Cancer Center /ID# 243673

🇺🇸

Miami, Florida, United States

Moffitt Cancer Center /ID# 243437

🇺🇸

Tampa, Florida, United States

University of Maryland, Baltimore /ID# 243679

🇺🇸

Baltimore, Maryland, United States

Dana-Farber Cancer Institute /ID# 249529

🇺🇸

Boston, Massachusetts, United States

University of Massachusetts - Worcester /ID# 243977

🇺🇸

Worcester, Massachusetts, United States

University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 243438

🇺🇸

Ann Arbor, Michigan, United States

The Valley Hospital /ID# 243829

🇺🇸

Paramus, New Jersey, United States

Rutenberg Cancer Center /ID# 244647

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Cancer Center /ID# 244656

🇺🇸

New York, New York, United States

Levine Cancer Institute /ID# 242851

🇺🇸

Charlotte, North Carolina, United States

University of Texas Southwestern Medical Center /ID# 243273

🇺🇸

Dallas, Texas, United States

Huntsman Cancer Institute /ID# 242872

🇺🇸

Salt Lake City, Utah, United States

University of Washington /ID# 243172

🇺🇸

Seattle, Washington, United States

Froedtert Memorial Lutheran Hospital /ID# 242654

🇺🇸

Milwaukee, Wisconsin, United States

Calvary Mater Newcastle /ID# 243730

🇦🇺

Waratah, New South Wales, Australia

Monash Health - Monash Medical Centre /ID# 244403

🇦🇺

Clayton, Victoria, Australia

St Vincent's Hospital Melbourne /ID# 256879

🇦🇺

Fitzroy Melbourne, Victoria, Australia

Peter MacCallum Cancer Ctr /ID# 256880

🇦🇺

Melbourne, Victoria, Australia

Epworth Healthcare /ID# 243734

🇦🇺

Richmond, Victoria, Australia

Fiona Stanley Hospital /ID# 244753

🇦🇺

Murdoch, Western Australia, Australia

Universitaetsklinikum Tuebingen /ID# 242815

🇩🇪

Tubingen, Baden-Wuerttemberg, Germany

Universitaetsklinikum Wuerzburg /ID# 242826

🇩🇪

Wuerzburg, Bayern, Germany

Universitaetsklinikum Essen /ID# 242819

🇩🇪

Essen, Germany

Universitaetsklinikum Hamburg-Eppendorf /ID# 243141

🇩🇪

Hamburg, Germany

Universitaetsklinikum Regensburg /ID# 242837

🇩🇪

Regensburg, Germany

IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 242581

🇮🇹

Bologna, Emilia-Romagna, Italy

IRCCS Ospedale San Raffaele /ID# 242583

🇮🇹

Milan, Milano, Italy

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 242584

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Meldola, Reggio Emilia, Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 242582

🇮🇹

Rome, Roma, Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico /ID# 244057

🇮🇹

Milano, Italy

Nagoya City University Hospital /ID# 249094

🇯🇵

Nagoya shi, Aichi, Japan

National Cancer Center Hospital East /ID# 245889

🇯🇵

Kashiwa-shi, Chiba, Japan

Hokkaido University Hospital /ID# 245966

🇯🇵

Sapporo-shi, Hokkaido, Japan

Kanazawa University Hospital /ID# 246812

🇯🇵

Kanazawa-shi, Ishikawa, Japan

Okayama Medical Center /ID# 245882

🇯🇵

Okayama-shi, Okayama, Japan

Yamagata University Hospital /ID# 245888

🇯🇵

Yamagata-shi, Yamagata, Japan

Szpital Wojewodzki w Opolu sp. z o.o. /ID# 243954

🇵🇱

Opole, Dolnoslaskie, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu /ID# 243246

🇵🇱

Wroclaw, Dolnoslaskie, Poland

Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie /ID# 243500

🇵🇱

Lublin, Lubelskie, Poland

Uniwersyteckie Centrum Kliniczne /ID# 243249

🇵🇱

Gdansk, Pomorskie, Poland

Hospital Duran i Reynals /ID# 242979

🇪🇸

Hospitalet de Llobregat, Barcelona, Spain

Clinica Universidad de Navarra - Pamplona /ID# 242977

🇪🇸

Pamplona, Navarra, Spain

Hospital Universitario Vall d'Hebron /ID# 242976

🇪🇸

Barcelona, Spain

Hospital Clinic de Barcelona /ID# 242978

🇪🇸

Barcelona, Spain

CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 244145

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre /ID# 242975

🇪🇸

Madrid, Spain

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