Multiple myeloma (MM) is a cancer of the blood's plasma cells. The cancer is typically found in the bones and bone marrow (the spongy tissue inside of the bones) and can cause bone pain, fractures, infections, weaker bones, and kidney failure. Treatments are available, but MM can come back (relapsed) or may not get better (refractory) with treatment. This is a study to determine the safety, efficacy, and pharmacokinetics of Etentamig in adult participants with MM. Etentamig is an investigational drug being developed for the treatment of MM. This study is broken into 4 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants will receive escalating doses of etentamig alone or in combination with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R). This will be followed by etentamig at the dose levels established during the escalation phases alone or in combination with DR, Kd, R. The participants can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Around 440 adult participants with MM will be enrolled at approximately 50 sites worldwide In all substudies, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or in combination with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or in combination with IV and oral DRd, DKd, or R. The study duration is approximately 130 months. 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 a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and questionnaires.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
440
Intravenous (IV) Infusion
Oral Capsule
IV Injection
Subcutaneous Injection
Oral Tablet
IV Infusion
Colorado Blood Cancer Institute /ID# 273129
Denver, Colorado, United States
RECRUITINGMoffitt Cancer Center /ID# 272628
Tampa, Florida, United States
RECRUITINGWinship Cancer Institute of Emory University /ID# 274830
Atlanta, Georgia, United States
RECRUITINGWeill Cornell Medical College /ID# 272517
New York, New York, United States
Number of Participants with Adverse Events (AE)s
An adverse event 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.
Time frame: Up to Approximately 130 Months
Substudy 1: Dose-Limiting Toxicity (DLT) of Etentamig + Daratumumab and Lenalidomide (DR) in Participants with Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI NDMM)
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Time frame: Up to Approximately 8 weeks
Substudy 2: DLT of Etentamig Monotherapy as Maintenance in Participants with Transplant-Eligible Newly Diagnosed Multiple Myeloma (TE NDMM)
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Time frame: Up to Approximately 8 Weeks
Substudy 3: DLT of Etentamig +Carfilzomib and Dexamethasone (Kd) Combination in Participants with Relapsed or Refractory Multiple Myeloma (RR MM)
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Time frame: Up to Approximately 8 Weeks
Substudy 4: DLT of Etentamig plus Lenalidomide when Given as Maintenance in Participants with TE NDMM
DLT events are defined as clinically significant adverse events or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications.
Time frame: Up to Approximately 8 Weeks
Substudy 1, 2, 3, 4: Complete Response Rate
Complete response rate is defined as complete response (CR), stringent complete response (sCR) as assessed by the international myeloma working group (IMWG) 2016 criteria for MM.
Time frame: Up to Approximately 1 Year
Substudy 1, 2, 3, 4: Overall Response Rate (ORR)
The ORR is defined as the percentage of participants who achieve a best overall response of confirmed PR or better determined by IMWG criteria, prior to the initiation of subsequent myeloma therapy.
Time frame: Up to Approximately 1 Year
Substudy 1, 2, 3, 4: 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 (determined by the IMWG) or death.
Time frame: Up to Approximately 130 Months
Substudy 1, 2, 3, 4: Duration of Response (DOR)
DOR is defined as the time from the date of first response to the earliest occurrence of progressive disease, or death, whatever occurs first.
Time frame: Up to Approximately 130 Months
Substudy 1, 2, 3, 4: Time-to-Progression (TTP)
TTP will be defined as the number of days from the date of first dose to the date of earliest disease progression.
Time frame: Up to Approximately 130 Months
Substudy 1, 2, 3, 4: Minimal Residual Disease (MRD) negativity
The MRD negativity rate is defined as the proportion of participants who achieve MRD negative status.
Time frame: Up to Approximately 52 Weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of North Carolina at Chapel Hill /ID# 274667
Chapel Hill, North Carolina, United States
RECRUITINGAtrium Health Levine Cancer Institute /ID# 276193
Charlotte, North Carolina, United States
RECRUITINGAtrium Health Wake Forest Baptist Medical Center /ID# 274847
Winston-Salem, North Carolina, United States
RECRUITINGOncology Hematology Care - Kenwood /ID# 272918
Cincinnati, Ohio, United States
RECRUITINGCoffs Harbour Health Campus /ID# 272010
Coffs Harbour, New South Wales, Australia
RECRUITINGPort Macquarie Base Hospital /ID# 275925
Port Macquarie, New South Wales, Australia
RECRUITING...and 15 more locations