First RR multiple myeloma patient treated with ABBV-383

Phase 3 trial tests safety, efficacy of therapy in relapsed or refractory cases

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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A Phase 3 clinical trial evaluating the safety and efficacy of AbbVie’s experimental therapy ABBV-383 in adults with relapsed or refractory multiple myeloma (RRMM) has treated its first patient.

Called CERVINO (NCT06158841), the study plans to enroll up to 380 patients, ages 18 and older, at 140 sites globally. For now, only four sites in Israel and one in Taiwan are recruiting patients, but U.S. sites may eventually open.

Eligible patients must have received at least two lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor. Their Eastern Cooperative Oncology Group performance status must be no greater than 2, meaning they must at least be able to walk and care for themselves.

“The start of the CERVINO Phase 3 trial marks an important step forward in AbbVie’s continued commitment to advance new oncology treatments and elevate the standard of care for blood cancer patients,” Mariana Cota Stirner, MD, PhD, AbbVie’s vice president, said in a company press release.

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Multiple myeloma is a blood cancer that develops from abnormal, uncontrolled growth of plasma cells, a type of immune cell that produces antibodies. It starts in the bone marrow and is likely to spread throughout the body, causing a range of symptoms.

While there are many available treatment options for multiple myeloma, the cancer can be difficult to treat because it is often refractory, meaning it does not respond to treatment, or relapsing, meaning it comes back after treatment.

“Despite notable advances in treatment, most patients with multiple myeloma will eventually relapse,” said Peter Voorhees, MD, clinical professor of medicine and director of plasma cell disorders at Atrium Health Levine Cancer Institute in Charlotte, North Carolina.

Moreover, “patients with advanced disease, especially in the community setting, often have limited access to novel treatment options and existing options have a high treatment burden, including frequent dosing,” Voorhees added.

The trial and its basis

ABBV-383, formerly TNB-383B, is a bispecific antibody that was originally developed by TeneoOne and acquired by AbbVie in 2021.

A bispecific antibody is one that binds to two targets at the same time. ABBV-383 specifically binds to B-cell maturation antigen (BCMA), which is abundant on the surface of plasma cells, and CD3, a protein found on immune T-cells.

It is expected to redirect immune cells to BCMA-positive myeloma cells, triggering a cancer-destroying attack. ABBV-383’s unique design is also anticipated to destroy plasma cells without mounting too strong an immune response.

Data from a Phase 1 trial (NCT03933735), when it involved 124 adults with heavily treated RRMM, showed that ABBV-383 was tolerated well when infused intravenously, or into a vein, once every three weeks at doses ranging from 0.025 to 120 mg.

Twelve (10%) patients stopped treatment and 46 (37%) interrupted it for some time because of adverse events. The most common side effects were cytokine release syndrome, which occurs when the immune system responds too strongly (57%), lower counts of a type of immune cell called neutrophils (37%), and fatigue (30%).

After a median 10.8 months, or nearly one year, on ABBV-383, 57% of patients showed what was considered a partial or complete response to treatment. Of the 51 patients given the 60 mg dose, 49 had efficacy data available. Their response rate was 59%.

Building on these findings, patients who take part in the CERVINO Phase 3 trial are being randomly assigned to receive either a once-monthly intravenous infusion of 60 mg of ABBV-383 or standard treatment, until the cancer progresses or treatment is stopped for other reasons.

“ABBV-383 is being evaluated with monthly dosing from the beginning of treatment, with the goal of maximizing treatment simplicity for physicians and patients, if proven in the clinical trials,” said Cota Stirner, who doubles as AbbVie’s therapeutic area head of oncology and hematology.

Standard treatment, chosen by the trial’s investigators, may include a combination of Kyprolis (carfilzomib) plus dexamethasone, Empliciti (elotuzumab) plus Pomalyst (pomalidomide) and dexamethasone, or Xpovio (selinexor) plus bortezomib (sold as Velcade and generics) and dexamethasone.

The main goal is to watch for differences in progression-free survival, or how long patients live without the cancer getting worse, and response rates for up to five years. Secondary goals include overall survival; other measures or response; changes in symptoms, physical functioning, and quality of life; and measures of safety.