Teclistamab

AbbVie released positive phase 3 data Thursday showing that its bispecific T-cell engager etentamig improved response rates and progression-free survival in patients with relapsed/refractory multiple myeloma. The monthly dosing schedule demonstrated low rates of cytokine release syndrome (CRS) and fatal infections, with the potential to enable treatment in outpatient and community-based settings. “The evolution of multiple myeloma has been one of going from a state of incurable disease, which for the large part it still is, to a place where now it's almost a chronic disease where patients are living longer,” Daejin Abidoye, M.D., vice president and therapeutic area head, oncology, solid tumor and hematology at AbbVie, told Fierce. “Being able to improve upon therapies and therapeutic modalities today that allow patients not only to live longer but to live better, fuller lives, has become a focus for us.” Multiple myeloma is a blood cancer that starts in plasma cells in the bone marrow and can cause bone pain, fractures and infections. More than 130,000 new cases are diagnosed worldwide each year. Although treatment has improved significantly, multiple myeloma remains largely incurable, and most patients eventually relapse. The phase 3 Cervino trial is a randomized, open-label study comparing monthly intravenous etentamig (ABBV-383) with investigator-selected standard available therapies in patients with relapsed/refractory multiple myeloma. Patients had received at least two prior lines of therapy and had been exposed to a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody. At the data cutoff, the trial included 393 patients who had received a median of three prior lines of therapy. After a median follow-up of 11.4 months, patients treated with etentamig had a 74% objective response rate, compared with 45.7% for those treated with standard available therapies. Etentamig also significantly improved progression-free survival, reducing the risk of disease progression or death by 60% compared with standard available therapies. The progression-free survival benefit was observed across all prespecified subgroups evaluated. The 12-month overall survival rate was 87.9% for patients receiving etentamig, compared with 72% for those receiving standard therapies. However, the prespecified efficacy boundary for overall survival had not been crossed at the data cutoff. With a single step-up dose followed by monthly dosing, etentamig demonstrated what AbbVie described as a potentially differentiated safety profile. Grade 3 or 4 infections occurred in 27.7% of patients receiving etentamig and 19.2% of those receiving standard available therapies. Grade 5 infections occurred in 1.5% of patients receiving etentamig, compared with 3.1% of those receiving standard therapies. Among patients receiving the single step-up dose, the incidence of CRS was 28.3% and was predominantly grade 1, with no grade 3 or higher events reported. One patient experienced grade 1 immune effector cell-associated neurotoxicity syndrome, or ICANS, with no grade 2 or higher events reported. Treatment discontinuations related to treatment-emergent adverse events occurred in 3.6% of patients receiving etentamig, compared with 9.6% of those receiving standard therapies. The data come from the first planned efficacy interim analysis of Cervino. Based on the results, the study’s independent data monitoring committee recommended unblinding the trial. The full results will be presented in a plenary session at the International Myeloma Society Annual Meeting, taking place Sept. 23-26 in Glasgow, Scotland. AbbVie also plans to discuss the results with global regulatory authorities to determine next steps for etentamig. Etentamig is an investigational second-generation B-cell maturation antigen (BCMA)xCD3 bispecific antibody T-cell engager. The drug is designed with a high-avidity, bivalent BCMA-binding domain that targets BCMA on malignant plasma cells and a low-affinity CD3-binding domain designed to engage T cells while reducing CRS and infections. It also retains neonatal Fc receptor (FcRn) binding, which enables monthly dosing after a single step-up dose. AbbVie notes that clinical correlations between these structural features and their effects have not been fully established. “We now have increased binding, which is critical for that tumor cell and multiple myeloma cell antigen, as well as the T cell. We have decreased immune activation with the CD3 in terms of the CRS, and attenuation of activity through the retained FcRn, which allows for longer dosing,” Abidoye said. “So here you have a proven modality of therapy that has now been improved upon, that offers more convenience for patients as well as a better safety profile.” In addition to multiple myeloma, AbbVie is pursuing etentamig in AL amyloidosis, a rare disease driven by abnormal plasma cells. Although the BCMA space is crowded with Johnson & Johnson’s Tecvayli, Pfizer’s Elrexfio and Bristol Myers Squibb’s CAR-T cell therapy Abecma, adverse events associated with BCMA-targeted treatments remain a challenge. CRS, neurotoxicity and infections, as well as the need for specialized monitoring and treatment infrastructure, can limit access to bispecific antibodies and CAR-T therapies, particularly in community settings. In 2021, Pfizer paused enrollment in a pivotal phase 2 trial of its anti-BCMA bispecific antibody elranatamab after seeing three cases of peripheral neuropathy in an earlier-stage study. Amgen also bowed out of the BCMA race in 2022 after pausing a phase 1 trial of its bispecific pavurutamab and later deciding to stop development and focus its R&D spending on other candidates. More recently, in July 2024, Bristol Myers Squibb decided to axe development of its multiple myeloma bispecific alnuctamab shortly after beginning a phase 3 trial. In June 2025, Cullinan penned a $700 million biobucks deal for Genrix Bio’s BCMAxCD3 bispecific T-cell engager, which the biotech planned to pair with its existing CD19 candidate.

AbbVie's investigational BCMA×CD3 bispecific etentamig (ABBV-383) has delivered a Phase III win in multiple myeloma, potentially giving the late entrant a foothold in an increasingly crowded class.In the CERVINO trial, etentamig produced a 74% objective response rate versus 45.7% with investigator's choice of standard available therapies and reduced the risk of disease progression or death by 60% in patients with triple-class exposed relapsed/refractory multiple myeloma. The study met both primary endpoints of response rate and progression-free survival, prompting an independent monitoring committee to recommend unblinding the trial at its first planned efficacy interim analysis.Overall survival (OS) at 12 months also favoured etentamig at 87.9% versus 72%, though AbbVie said the prespecified efficacy boundary for OS had not been crossed at the data cutoff.The trial enrolled 421 patients who received at least two prior lines of therapy, including exposure to a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody. They were randomised to receive etentamig administered once every four weeks or investigator's choice of standard available therapies, including Kyprolis (carfilzomib) plus dexamethasone, Empliciti (elotuzumab) plus pomalidomide and dexamethasone, or Xpovio (selinexor) plus bortezomib and dexamethasone.Dosing, safety advantages?The results put etentamig on track to become a potential fourth BCMA×CD3 bispecific on the market, following Johnson & Johnson's Tecvayli (teclistamab), Pfizer's Elrexfio (elranatamab) and Regeneron's Lynozyfic (linvoseltamab).However, AbbVie is betting dosing convenience might be a key differentiator. Etentamig is administered following a single step-up dose and then every four weeks right from the start of treatment."Etentamig is going to be fourth to market…However, [with the marketed bispecifics] we are now admitting fewer patients for the ramp-up [step-up], and we are not sticking to the FDA dosing schedule; we usually still use them once a week for two months and then once every other week for four months," noted one key opinion leader (KOL) in a recent FirstWord report (see – KOL Insight - Multiple Myeloma). "Nevertheless, etentamig could still gain traction because an FDA-approved label of once-a-month administration right from the start could have an advantage," the KOL said.Another highlighted that etentamig's structure "is different because the Fc region has been silenced, and so the safety profile, in principle, is better than that of the other bispecifics in terms of CRS (cytokine release syndrome)."Among patients receiving the single step-up dose in the CERVINO study, CRS occurred in 28.3%, predominantly grade 1, with no grade 3 or higher cases; grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in one patient (0.9%), with no grade 2 or higher events.Grade 3/4 infections were more common with etentamig than standard therapies (27.7% vs. 19.2%), but grade 5 infections were half as frequent (1.5% vs. 3.1%).Treatment-related adverse-event discontinuations were also lower with etentamig than standard therapies, at 3.6% versus 9.6%. AbbVie says the profile could potentially allow treatment to move beyond specialised centres and into outpatient and community settings.Early-stage data based on 82 evaluable patients presented at last year's American Society of Hematology (ASH) meeting showed etentamig plus pomalidomide and dexamethasone produced an 81% response rate. CRS occurred in 37% of patients after receiving the etentamig target dose, with events either grade 1 or 2 and no grade ≥3 events. Two deaths, due to influenza and worsening renal failure, were possibly related to etentamig treatment.Full CERVINO results will be presented at the International Myeloma Society (IMS) annual meeting later this month.