ABBV-383 for Multiple Myeloma
Recruiting in Palo Alto (17 mi)
+54 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: TeneoOne Inc.
Must be taking: Proteasome inhibitors, IMiDs, Anti-CD38
Must not be taking: BCMA-targeted therapy
Disqualifiers: Rapidly progressing disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests ABBV-383, a new drug for adults with multiple myeloma that has come back or not responded to other treatments. The drug is given through an IV regularly. The study will monitor the drug's effects and any side effects over several years.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
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 is known about the safety of ABBV-383 for treating multiple myeloma?
In a phase I study, ABBV-383 was tested in patients with relapsed or refractory multiple myeloma, and the safety outcomes were reported. Additionally, a similar bispecific antibody, TNB-383B, showed mild increases in cytokines (proteins involved in cell signaling) associated with immune responses, suggesting some inflammatory effects but no severe safety concerns.
12346What makes the drug ABBV-383 unique for treating multiple myeloma?
ABBV-383 is a novel bispecific antibody that targets both B-cell maturation antigen (BCMA) and CD3, effectively redirecting T cells to attack multiple myeloma cells. This dual-targeting approach is unique because it engages the body's own immune cells to specifically kill cancer cells, offering a promising option for patients with relapsed or refractory multiple myeloma.
13456Eligibility Criteria
Adults with Multiple Myeloma that has returned or hasn't improved after treatment can join. They must have had at least 2-3 prior treatments, including specific drugs like proteasome inhibitors and anti-CD38 antibodies. For one part of the study, they shouldn't have had BCMA-targeted therapy before.Inclusion Criteria
You must have a disease that can be measured according to the study guidelines.
I have never been treated with ABBV-383.
I've had 3+ treatments including PI, IMiD, and anti-CD38 for my condition.
+3 more
Exclusion Criteria
I have received therapy targeting BCMA.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive ABBV-383 as an infusion into the vein in 28 day cycles for approximately 3 years
3 years
Regular visits at a hospital or clinic
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing ABBV-383, a new drug for relapsed/refractory Multiple Myeloma. It's given by IV in two parts: first finding the right starting dose then expanding to more patients; another group gets a fixed dose. The study lasts about 3 years with regular hospital visits.
4Treatment groups
Experimental Treatment
Group I: Arm C: ABBV-383 Step UpExperimental Treatment1 Intervention
Participants will receive step up dose and full target dose of ABBV-383 in 28 day cycles.
Group II: Arm B: ABBV-383 BCMA ExposedExperimental Treatment1 Intervention
Participants previously exposed to BCMA-targeted agents will receive ABBV-383 Dose A in 28 day cycles.
Group III: Arm A (Part 2): ABBV-383 Dose ExpansionExperimental Treatment1 Intervention
BCMA naïve participants will receive the dose of ABBV-383 dose A in 28 day cycles.
Group IV: Arm A (Part 1): ABBV-383 Dose EscalationExperimental Treatment1 Intervention
B-cell maturation antigen (BCMA) naïve participants will receive different doses of ABBV-383 in 28 day cycles.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cross Cancer Institute /ID# 252056Edmonton, Canada
Oncology Consultants /ID# 268323Houston, TX
Tulane University School of Medicine /ID# 251204New Orleans, LA
Wake Forest Univ HS /ID# 251165Winston-Salem, NC
More Trial Locations
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Who Is Running the Clinical Trial?
TeneoOne Inc.Lead 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.