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

Sponsor

TeneoOne Inc. (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05259839

Collaborator

(none)

270

Enrollment

Locations

Arms

84.4

Anticipated Duration (Months)

5.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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 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.

Condition or Disease	Intervention/Treatment	Phase
Relapsed/Refractory Multiple Myeloma	Drug: ABBV-383 Drug: Dexamethasone Drug: Lenalidomide Drug: Pomalidomide Drug: Nirogacestat Drug: Daratumumab	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

270 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 18, 2022

Anticipated Primary Completion Date :

Oct 31, 2029

Anticipated Study Completion Date :

Oct 31, 2029

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose Limiting Toxicities (DLT) of ABBV-383 [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 Outcome Measures

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 Disease Negativity (MRD) [Up to Approximately 3 Years]
MRD is defined as the percentage of participants with assessment of the minimal residual disease.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences /ID# 243096	Little Rock	Arkansas	United States	72205
2	Sylvester Comprehensive Cancer Center /ID# 243673	Miami	Florida	United States	33136-1002
3	Moffitt Cancer Center /ID# 243437	Tampa	Florida	United States	33612-9416
4	University of Maryland School of Medicine /ID# 243679	Baltimore	Maryland	United States	21201-1509
5	University of Massachusetts - Worcester /ID# 243977	Worcester	Massachusetts	United States	01655
6	University of Michigan Comprehensive Cancer Center Michigan Medicine /ID# 243438	Ann Arbor	Michigan	United States	48109
7	The Valley Hospital /ID# 243829	Paramus	New Jersey	United States	07652
8	Rutenberg Cancer Center /ID# 244647	New York	New York	United States	10029-6030
9	Memorial Sloan Kettering Cancer Center /ID# 244656	New York	New York	United States	10065-6007
10	Levine Cancer Institute, Atrium Health /ID# 242851	Charlotte	North Carolina	United States	28204-2812
11	University of Texas Southwestern Medical Center /ID# 243273	Dallas	Texas	United States	75390-7208
12	Huntsman Cancer Institute /ID# 242872	Salt Lake City	Utah	United States	84112-5500
13	University of Washington /ID# 243172	Seattle	Washington	United States	98109
14	Froedtert Memorial Lutheran Hospital /ID# 242654	Milwaukee	Wisconsin	United States	53226-3522
15	St George Hospital /ID# 243740	Kogarah	New South Wales	Australia	2217
16	Calvary Mater Newcastle /ID# 243730	Waratah	New South Wales	Australia	2298
17	Monash Medical Centre /ID# 244403	Melbourne	Victoria	Australia	3168
18	Epworth Healthcare /ID# 243734	Richmond	Victoria	Australia	3121
19	Fiona Stanley Hospital /ID# 244753	Murdoch	Western Australia	Australia	6150
20	Universitaetsklinikum Tuebingen /ID# 242815	Tubingen	Baden-Wuerttemberg	Germany	72076
21	Universitaetsklinikum Essen /ID# 242819	Essen		Germany	45147
22	Universitaetsklinikum Hamburg-Eppendorf (UKE) /ID# 243141	Hamburg		Germany	20246
23	Universitaetsklinikum Regensburg /ID# 242837	Regensburg		Germany	93042
24	Universitaetsklinikum Wuerzburg /ID# 242826	Wuerzburg		Germany	97080
25	Fondazione Policlinico Universitario Agostino Gemelli IRCCS-Università Cattolica /ID# 242582	Rome	Lazio	Italy	00168
26	Ospedale San Raffaele IRCCS /ID# 242583	Milan	Lombardia	Italy	20132
27	IRCCS Azienda Ospedaliero-Universitaria di Bologna /ID# 242581	Bologna		Italy	40138
28	Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRCCS /ID# 242584	Meldola		Italy	47014
29	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico /ID# 244057	Milan		Italy	20122
30	National Cancer Center Hospital East /ID# 245889	Kashiwa-shi	Chiba	Japan	277-8577
31	Hokkaido University Hospital /ID# 245966	Sapporo-shi	Hokkaido	Japan	060-8648
32	Kanazawa University Hospital /ID# 246812	Kanazawa-shi	Ishikawa	Japan	920-8641
33	Okayama Medical Center /ID# 245882	Okayama-shi	Okayama	Japan	701-1192
34	Yamagata University Hospital /ID# 245888	Yamagata-shi	Yamagata	Japan	990-9585
35	Szpital Wojewodzki w Opolu sp. z o.o. /ID# 243954	Opole	Dolnoslaskie	Poland	45-372
36	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wrocławiu /ID# 243246	Wroclaw	Dolnoslaskie	Poland	50-556
37	Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie /ID# 243500	Lublin	Lubelskie	Poland	20-081
38	Uniwersyteckie Centrum Kliniczne /ID# 243249	Gdansk	Pomorskie	Poland	80-214
39	Pratia Onkologia Katowice /ID# 243247	Katowice		Poland	40-519
40	Hospital Duran i Reynals /ID# 242979	Hospitalet de Llobregat	Barcelona	Spain	08907
41	CLINICA UNIVERSIDAD DE NAVARRA-Pamplona /ID# 242977	Pamplona	Navarra	Spain	31008
42	Hospital Universitario Vall d'Hebron /ID# 242976	Barcelona		Spain	08035
43	Hospital Clinic de Barcelona /ID# 242978	Barcelona		Spain	08036
44	CLINICA UNIVERSIDAD DE NAVARRA-Madrid /ID# 244145	Madrid		Spain	28027
45	Hospital Universitario 12 de Octubre /ID# 242975	Madrid		Spain	28041
46	Hospital Universitario Virgen del Rocio /ID# 242974	Sevilla		Spain	41013