Clinical trial NCT05259839: 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
Official title: A Dose Escalation and Expansion Study of Etentamig (ABBV-383) in Combination With Anti-Cancer Regimens for the Treatment of Patients With Newly Diagnosed or Relapsed/Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Multiple Myeloma
Keywords: Relapsed/Refractory Multiple Myeloma
Pomalidomide
Dexamethasone
Lenalidomide
Daratumumab
Nirogacestat
Etentamig
ABBV-383
Cancer
Lead sponsor: TeneoOne Inc.
Sponsor class: INDUSTRY
First posted: 2022-03-02
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLT) of Etentamig
timeFrame: Up to approximately 28 Days
measure: Number of Participants with Adverse Events (AEs)
timeFrame: Up to Approximately 3 Years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to Approximately 3 Years
measure: Progression-Free Survival (PFS)
timeFrame: Up to Approximately 3 Years
measure: Duration of Response (DOR)
timeFrame: Up to Approximately 3 Years
measure: Time-to-Progression (TTP)
timeFrame: Up to Approximately 3 Years
measure: Percentage of Participants with Minimal Residual Diseas (MRD) Negativity by Next-Generation Sequencing (NGS)
timeFrame: Up to Approximately 3 Years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences /ID# 243096
state: Arkansas
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center /ID# 243673
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center /ID# 243437
state: Florida
city: Baltimore
country: United States
facility: University of Maryland, Baltimore /ID# 243679
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute /ID# 249529
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts - Worcester /ID# 243977
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 243438
state: Michigan
city: Paramus
country: United States
facility: The Valley Hospital /ID# 243829
state: New Jersey
city: New York
country: United States
facility: Rutenberg Cancer Center /ID# 244647
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center /ID# 244656
state: New York
city: Charlotte
country: United States
facility: Levine Cancer Institute /ID# 242851
state: North Carolina
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center /ID# 243273
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute /ID# 242872
state: Utah
city: Seattle
country: United States
facility: University of Washington /ID# 243172
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Memorial Lutheran Hospital /ID# 242654
state: Wisconsin
city: Kogarah
country: Australia
facility: St George Hospital /ID# 243740
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle /ID# 243730
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health - Monash Medical Centre /ID# 244403
state: Victoria
city: Fitzroy Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne /ID# 256879
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Ctr /ID# 256880
state: Victoria
city: Richmond
country: Australia
facility: Epworth Healthcare /ID# 243734
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital /ID# 244753
state: Western Australia
city: Tubingen
country: Germany
facility: Universitaetsklinikum Tuebingen /ID# 242815
state: Baden-Wuerttemberg
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg /ID# 242826
state: Bayern
city: Essen
country: Germany
facility: Universitaetsklinikum Essen /ID# 242819
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf /ID# 243141
city: Regensburg
country: Germany
facility: Universitaetsklinikum Regensburg /ID# 242837
city: Bologna
country: Italy
facility: IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 242581
state: Emilia-Romagna
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele /ID# 242583
state: Milano
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST - IRCCS /ID# 242584
state: Reggio Emilia
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 242582
state: Roma
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico /ID# 244057
city: Nagoya shi
country: Japan
facility: Nagoya City University Hospital /ID# 249094
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East /ID# 245889
state: Chiba
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital /ID# 245966
state: Hokkaido
city: Kanazawa-shi
country: Japan
facility: Kanazawa University Hospital /ID# 246812
state: Ishikawa
city: Okayama-shi
country: Japan
facility: Okayama Medical Center /ID# 245882
state: Okayama
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital /ID# 245888
state: Yamagata
city: Opole
country: Poland
facility: Szpital Wojewodzki w Opolu sp. z o.o. /ID# 243954
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu /ID# 243246
state: Dolnoslaskie
city: Lublin
country: Poland
facility: Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie /ID# 243500
state: Lubelskie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne /ID# 243249
state: Pomorskie
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals /ID# 242979
state: Barcelona
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra - Pamplona /ID# 242977
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron /ID# 242976
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona /ID# 242978
city: Madrid
country: Spain
facility: CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 244145
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre /ID# 242975
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio /ID# 242974
Study officials:
affiliation: TeneoOne Inc.
name: TeneoOne Inc
role: STUDY_DIRECTOR
References: