A Study to Assess Change in Disease Activity and Adverse Events (AE)s in Adult Participants With Multiple Myeloma Receiving T Cell Engaging Bi/Tri-specific Antibodies Intravenously (IV)/Subcutaneously (SC) Alone or in Combinations

Official title

A Phase 1/2, Open-Label, Platform Study to Evaluate Safety and Efficacy of T Cell Engaging Bi/Tri-specific Antibodies in Subjects With MM

Overview

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 and ABBV-2001 in adult participants with MM. Etentamig and ABBV-2001 are investigational drugs being developed for the treatment of MM. This study is broken into 6 substudies and each substudy consists of a dose escalation phase and dose expansion phase. Participants in substudies 1-4 will receive escalating doses of etentamig alone or with daratumumab and lenalidomide (DR), carfilzomib and dexamethasone (Kd) or lenalidomide (R), followed by etentamig at the dose levels established during the escalation phases alone or with DR, Kd, R. Participants in substudies 1-4 can also receive daratumumab, lenalidomide and dexamethasone (DRd), R, or daratumumab, carfilzomib, and dexamethasone (DKd) as a comparator in the dose expansion phases. Participants in substudies 5-6 will receive escalating doses or at the dose levels established during the escalation phases of ABBV-2001 with iberdomide or mezigdomide. Around 602 adult participants with MM will be enrolled at approximately 75 sites worldwide In substudies 1-3, participants will receive escalating doses of etentamig as Intravenous (IV) infusions, alone or with DR, R or Kd, followed by IV infusions of etentamig at the dose levels established during the escalation phases alone or with IV and DRd, DKd, or R. In substudie 4, participants will receive escalating doses of etentamig as Intravenous (IV) infusions followed by IV infusions of etentamig at the dose levels established during the escalation phase. In substudies 5-6, participants will receive escalating doses of ABBV-2001 as subcutaneous (SC) injections, with oral iberdomide or mezigdomide, followed by SC injections of ABBV-2001 at the dose levels established during the escalation phases with oral iberdomide or mezigdomide. 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.

Interventions

• Drug Etentamig
  Intravenous (IV) Infusion
• Drug Lenalidomide
  Oral
• Drug Dexamethasone
  IV Injection
• Drug Daratumumab
  Subcutaneous Injection
• Drug Dexamethasone
  Oral
• Drug Carfilzomib
  IV Infusion
• Drug Mezigdomide
  Oral
• Drug Iberdomide
  Oral
• Drug ABBV-2001
  subcutaneous (SC) Injection

Primary outcome measures

• Number of Participants with Adverse Events (AE)s [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) [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) [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) [Time frame: Up to Approximately 8 Weeks]
• Substudy 4: DLT of Etentamig plus Lenalidomide when Given as Maintenance in Participants with TE NDMM [Time frame: Up to Approximately 8 Weeks]
• Substudy 5: DLT of ABBV-2001 in Combination with Iberdomide in Participants with RR MM [Time frame: Up to Approximately 8 Weeks]
• Substudy 6: DLT of ABBV-2001 in Combination with Mezigdomide in Participants with RR MM [Time frame: Up to Approximately 8 Weeks]

Secondary outcome measures (6)

• Substudy 1, 2, 3, 4, 5, 6: Complete Response Rate [Time frame: Up to Approximately 1 Year]
• Substudy 1, 2, 3, 4, 5, 6: Overall Response Rate (ORR) [Time frame: Up to Approximately 1 Year]
• Substudy 1, 2, 3, 4, 5, 6: Progression Free Survival (PFS) [Time frame: Up to Approximately 130 Months]
• Substudy 1, 2, 3, 4, 5, 6: Duration of Response (DOR) [Time frame: Up to Approximately 130 Months]
• Substudy 1, 2, 3, 4, 5, 6: Time-to-Progression (TTP) [Time frame: Up to Approximately 130 Months]
• Substudy 1, 2, 3, 4, 5, 6: Minimal Residual Disease (MRD) negativity [Time frame: Up to Approximately 52 Weeks]

Eligibility criteria

Inclusion criteria

• Eastern cooperative oncology group (ECOG) performance of <= 1.
• Confirmed diagnosis of multiple myeloma (MM) according to the International Myeloma Working Group (IMWG) diagnostic criteria with either newly diagnosed or relapsed or refractory (RR) MM, depending on the substudy.

Exclusion criteria

• Participant who has known active central nervous system involvement of MM.
• Participant who has known active infection as outlined in the protocol.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 14 centers

• City of Hope National Medical Center /ID# 273132 — Duarte
• City of Hope - Orange County Lennar Foundation Cancer Center /ID# 277911 — Irvine
• Colorado Blood Cancer Institute /ID# 273129 — Denver
• Moffitt Cancer Center /ID# 272628 — Tampa
• Winship Cancer Institute of Emory University /ID# 274830 — Atlanta
• Mount Sinai - The Tisch Cancer Institute /ID# 272470 — New York
• Weill Cornell Medical College /ID# 272517 — New York
• University of North Carolina at Chapel Hill /ID# 274667 — Chapel Hill
• … and 6 more centers

Australia · 8 centers

• Coffs Harbour Health Campus /ID# 272010 — Coffs Harbour
• Port Macquarie Base Hospital /ID# 275925 — Port Macquarie
• Westmead Hospital /ID# 271880 — Westmead
• Icon Cancer Care - South Brisbane /ID# 271836 — South Brisbane
• Royal Adelaide Hospital /ID# 272629 — Adelaide
• St Vincent's Hospital - Melbourne /ID# 276451 — Fitzroy
• Peter MacCallum Cancer Centre. /ID# 272024 — Melbourne
• The Perth Blood Institute - West Perth /ID# 272469 — West Perth

Israel · 5 centers

• Rabin Medical Center. /ID# 271365 — Petah Tikva
• Soroka Medical Center /ID# 271367 — Beersheba
• The Chaim Sheba Medical Center /ID# 271366 — Ramat Gan
• Rambam Health Care Campus- Haifa /ID# 271364 — Haifa
• Hadassah Medical Center-Hebrew University /ID# 271362 — Jerusalem

Japan · 3 centers

• Nagoya City University Hospital /ID# 273529 — Nagoya
• University Hospital Kyoto Prefectural University of Medicine /ID# 275713 — Kyoto
• The University of Osaka Hospital /ID# 275791 — Suita-shi

United Kingdom · 3 centers

• Hammersmith Hospital /ID# 274615 — London
• University Hospitals Birmingham NHS Foundation Trust /ID# 274620 — Birmingham
• University Hospital of Wales /ID# 273446 — Cardiff

Norway · 1 center

• Oslo Universitetssykehus Ulleval /ID# 277915 — Oslo

Identifiers

NCT: NCT06892522 · M25-059 · 2024-515770-27-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗