ABBV-383 for Multiple Myeloma
(CERVINO Trial)
Recruiting in Palo Alto (17 mi)
+134 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: AbbVie
Must be taking: Proteasome inhibitors, Immunomodulatory imides
Must not be taking: BCMA-targeted therapy
Disqualifiers: Neurologic, Psychiatric, Cardiovascular, others
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?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 change in disease symptoms of etentamig compared to standard available therapies in adult participants with relapsed/refractory (R/R) MM.
Etentamig is an investigational drug being developed for the treatment of R/R MM. This study is broken into 2 Arms; Arm A and Arm B. In Arm A, participants will receive etentamig as a monotherapy. In Arm B, participants will receive the standard available therapy (SAT) identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. Around 380 adult participants with relapsed/refractory multiple myeloma will be enrolled at approximately 140 sites across the world.
In Arm A participants will receive etentamig as an infusion into the vein in 28 day cycles, during the 3.5 year study duration. In Arm B, participants will receive the SAT identified by the Investigator during screening, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable, during the 3.5 year study duration.
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.
Will I have to stop taking my current medications?
The trial information does not specify if you need to stop your current medications. However, in Arm B, you will receive standard available therapy based on your previous treatment history, which might mean continuing some existing medications.
What data supports the effectiveness of the drug ABBV-383 for treating multiple myeloma?
Research shows that ABBV-383, a bispecific antibody targeting BCMA and CD3, has shown promising results in early human trials for patients with relapsed or hard-to-treat multiple myeloma. Similar treatments targeting BCMA have demonstrated the ability to effectively kill multiple myeloma cells and activate the immune system to fight the cancer.
12345What safety data exists for ABBV-383 in humans?
In a phase I study, ABBV-383 was tested in patients with relapsed/refractory multiple myeloma and showed promising safety outcomes. Another study on a similar bispecific antibody, TNB-383B, indicated mild increases in cytokines (proteins involved in inflammation) but no significant safety concerns.
12346What makes the drug ABBV-383 unique for treating multiple myeloma?
ABBV-383 is a novel treatment for multiple myeloma that works by engaging the body's own T-cells to target and kill cancer cells. It is a bispecific antibody, meaning it can bind to two different targets: the B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T-cells, effectively redirecting the immune system to attack the cancer.
13456Eligibility Criteria
This trial is for adults with multiple myeloma that has returned or hasn't improved after treatment. They must have had at least two prior therapies, including specific inhibitors and antibodies, but not BCMA-targeted therapy. Participants need to be physically able to perform daily activities with some limitations (ECOG <=2) and meet certain lab criteria.Inclusion Criteria
I can do most of my daily activities on my own.
You have more than 200 milligrams of M-protein in your urine over a 24-hour period.
If you don't have a specific protein in your blood or urine, another type of protein in your blood needs to be above a certain level.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive etentamig or standard available therapy in 28-day cycles for up to 3.5 years
3.5 years
Regular visits at a hospital or clinic
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Participant Groups
The study compares ABBV-383 given intravenously in 28-day cycles against standard available therapies chosen by the investigator. It aims to see how well ABBV-383 works compared to these treatments over a period of 3.5 years in about 380 participants worldwide.
2Treatment groups
Experimental Treatment
Group I: Standard Available Therapy (SAT)Experimental Treatment6 Interventions
Participants will receive SAT, in accordance with the local (or applicable) approved label, package insert, summary of product characteristics, and/or the institutional guidelines, as applicable. SAT choices are carfilzomib + dexamethasone (Kd), elotuzumab + pomalidomide + dexamethasone (EloPd), selinexor + bortezomib + dexamethasone (SVd).
Group II: EtentamigExperimental Treatment1 Intervention
Participants will receive etentamig as a monotherapy.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University, Winship Cancer Institute /ID# 262525Atlanta, GA
Springfield Clinic /ID# 262266Springfield, IL
Center for Cancer and Blood Disorders /ID# 263637Bethesda, MD
New York Cancer & Blood Specialists - Bay Shore /ID# 261524Bay Shore, NY
More Trial Locations
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Who Is Running the Clinical Trial?
AbbVieLead Sponsor
References
A Phase I First-in-Human Study of ABBV-383, a B-Cell Maturation Antigen × CD3 Bispecific T-Cell Redirecting Antibody, in Patients With Relapsed/Refractory Multiple Myeloma. [2023]ABBV-383, a B-cell maturation antigen × CD3 T-cell engaging bispecific antibody, has demonstrated promising results in an ongoing first-in-human phase I study (ClinicalTrials.gov identifier: NCT03933735) in patients with relapsed/refractory multiple myeloma (RRMM). Herein, we report safety and efficacy outcomes of this phase I dose escalation/expansion study.
Bispecific antibodies and dual-targeting CAR-T cells for multiple myeloma: latest updates from the 2023 ASCO annual meeting. [2023]Bispecific antibodies (BsAbs) and dual-targeted chimeric antigen receptor T (CAR T) cells have been employed in relapsed/refractory multiple myeloma (RRMM) patients over the past few years, as an increasing number of patients were ineffectively treated by ≥ 3 prior lines of therapy. BCMA/CD3 and GPRC5D/CD3 are the most popular combinations. Clinical findings indicated that patients exhibit a greater susceptibility to stronger and more enduring responses. Here, we summarize the latest data from the 2023 ASCO annual meeting on BsAbs targeting BCMA/CD3, GPRC5D/CD3 and BCMA/CD19 CAR T cells.
Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. [2023]TNB-383B is a fully human BCMA-targeting T-cell engaging bispecific monoclonal antibody (T-BsAb). We assessed ex vivo efficacy of this drug to mediate killing of bone marrow mononuclear cells (BMMCs) freshly isolated from 10 patients with relapsed multiple myeloma (MM). BMMC were treated ex vivo with TNB-383B at doses ranging from 0.001-1 μg. Plasma cell (PC) lysis, viability, BCMA expression, CTL distribution, and degranulation were assessed by flow cytometry. Cytokine response to TNB-383B was quantified by multiplex protein assay. Dose-dependent PC lysis was triggered in all cases by TNB-383B at doses as low as 0.001 μg (P = .0102). Primary MM cells varied in BCMA expression. High BCMA+ PC count correlated with increased PC lysis (P = .005) and significant CTL degranulation specific to TNB-383B treatment (P = .0153 at 1 μg). High E:T ratio in bone marrow specimens led to lower viable and higher apoptotic PC compared with low E:T ratio (P < .001). Three cytokines were significantly modulated by TNB-383B: IL-2/TNFα increased by ∼4 ± 3.5-fold average (P < .005 at 1 μg) and IP10 increased by ∼50 ± 15-fold (P < .001 at 1 μg). We conclude that TNB-383B triggers primary PC lysis and CTL degranulation in a dose-dependent fashion ex vivo with no T cell expansion and mild increase of CRS-associated cytokines.
Bispecific BCMA-CD3 Antibodies Block Multiple Myeloma Tumor Growth. [2022]BCMA antigen is overexpressed in multiple myeloma cells and has been shown to be a promising target for novel cellular and antibody therapeutics. The humanized BCMA (clone 4C8A) antibody that effectively targeted multiple myeloma in a CAR (chimeric antigen receptor) format was used for designing several formats of bispecific BCMA-CD3 antibodies. Several different designs of univalent and bivalent humanized BCMA-CD3 CrossMAB and BCMA-FAB-CD3 ScFv-Fc antibodies were tested for binding with BCMA-positive cells and T cells and for killing by real time cytotoxic activity and IFN-gamma secretion with CHO-BCMA target cells and with multiple myeloma MM1S and H929 cell lines. All BCMA-CD3 antibodies demonstrated specific binding by FACS to CHO-BCMA, multiple myeloma cells, and to T cells with affinity Kd in the nM range. All antibodies with T cells specifically killed CHO-BCMA and multiple myeloma cells in a dose-dependent manner. The BCMA-CD3 antibodies with T cells secreted IFN-gamma with EC50 in the nM range. In addition, three BCMA bispecific antibodies had high in vivo efficacy using an MM1S xenograft NSG mouse model. The data demonstrate the high efficacy of novel hBCMA-CD3 antibodies with multiple myeloma cells and provide a basis for future pre-clinical and clinical development.
An anti-B cell maturation antigen bispecific antibody for multiple myeloma. [2015]The development of immunotherapies for multiple myeloma is critical to provide new treatment strategies to combat drug resistance. We report a bispecific antibody against B cell maturation antigen (BiFab-BCMA), which potently and specifically redirects T cells to lyse malignant multiple myeloma cells. BiFab-BCMA lysed target BCMA-positive cell lines up to 20-fold more potently than a CS1-targeting bispecific antibody (BiFab-CS1) developed in an analogous fashion. Further, BiFab-BCMA robustly activated T cells in vitro and mediated rapid tumor regression in an orthotopic xenograft model of multiple myeloma. The in vitro and in vivo activities of BiFab-BCMA are comparable to those of anti-BCMA chimeric antigen receptor T cell therapy (CAR-T-BCMA), for which two clinical trials have recently been initiated. A BCMA-targeted bispecific antibody presents a promising treatment option for multiple myeloma.
A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. [2021]CD3-engaging bispecific antibodies (bsAbs) and chimeric antigen receptor (CAR) T cells are potent therapeutic approaches for redirecting patient T cells to recognize and kill tumors. Here we describe a fully human bsAb (REGN5458) that binds to B-cell maturation antigen (BCMA) and CD3, and compare its antitumor activities vs those of anti-BCMA CAR T cells to identify differences in efficacy and mechanism of action. In vitro, BCMAxCD3 bsAb efficiently induced polyclonal T-cell killing of primary human plasma cells and multiple myeloma (MM) cell lines expressing a range of BCMA cell surface densities. In vivo, BCMAxCD3 bsAb suppressed the growth of human MM tumors in murine xenogeneic models and showed potent combinatorial efficacy with programmed cell death protein 1 blockade. BCMAxCD3 bsAb administration to cynomolgus monkeys was well tolerated, resulting in the depletion of BCMA+ cells and mild inflammatory responses characterized by transient increases in C-reactive protein and serum cytokines. The antitumor efficacy of BCMAxCD3 bsAb was compared with BCMA-specific CAR T cells containing a BCMA-binding single-chain variable fragment derived from REGN5458. Both BCMAxCD3 bsAb and anti-BCMA CAR T cells showed similar targeted cytotoxicity of MM cell lines and primary MM cells in vitro. In head-to-head in vivo studies, BCMAxCD3 bsAb rapidly cleared established systemic MM tumors, whereas CAR T cells cleared tumors with slower kinetics. Thus, using the same BCMA-binding domain, these results suggest that BCMAxCD3 bsAb rapidly exerts its therapeutic effects by engaging T cells already in place at the tumor site, whereas anti-BCMA CAR T cells require time to traffic to the tumor site, activate, and numerically expand before exerting antitumor effects.