Is There Hope for Trispecific Antibodies in Myeloma Care?

Trispecific antibodies have emerged as a promising new frontier in multiple myeloma treatment. 

Designed to engage multiple targets simultaneously, these therapies aim to improve tumor targeting and reduce the chances of cancer evading treatment. However, recent clinical trial results presented at the 2024 American Society of Hematology (ASH) Conference present a mixed picture—some disappointing, others more hopeful.

Early Challenges with Trispecific Antibodies

Initial trials using trispecific antibodies in relapsed/refractory multiple myeloma (RRMM) have faced significant hurdles. The first-in-human Phase 1 study of SAR442257, titled "1992 First-in-Human Phase 1 Study of SAR442257 in Patients with Relapsed/Refractory Multiple Myeloma and Non-Hodgkin Lymphoma," aimed to harness T-cell activation to fight myeloma. 

To learn more about this study, watch the video here: Tri-specific Antibody SAR442257 in RRMM and Non-Hodgkin Lymphoma | Fredrik Schjesvold

Unfortunately, the study was halted due to safety concerns. High rates of cytokine release syndrome (CRS), Epstein-Barr virus (EBV), and cytomegalovirus (CMV) reactivations and even a fatal case of CRS led to the early termination of the trial. Despite the innovative design, SAR442257 struggled with balancing efficacy and safety.

“While this is the end of [this clinical trial’s] story,” shares Fredrik Schjesvold, the primary investigator of the study, “it has also taught us a lot about how not to stimulate T-cells. Even though it worked in the lab, it didn’t work as we had hoped in the clinical trial.” 

Early Promising Results with ISB 2001

Despite this setback, tri-specific antibody research in myeloma is far from over. 

Encouraging early results from the Phase 1 trial of ISB 2001, titled "1026 First Results of a Phase 1, First-in-Human, Dose Escalation Study of ISB 2001, a BCMAxCD38xCD3 Targeting Trispecific Antibody in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)," offer renewed optimism. 

Unlike previous trials, ISB 2001 demonstrated a 75% overall response rate (ORR) among efficacy-evaluable patients. Even more promising, patients at doses as low as 50 μg/kg showed sustained responses, including stringent complete responses (sCR) and minimal residual disease (MRD)-negative outcomes.

Importantly, ISB 2001 was well-tolerated, with only mild to moderate cases of CRS and no dose-limiting toxicities (DLTs) reported up to the highest tested dose. These results suggest that carefully designed trispecific antibodies like ISB 2001 may successfully activate the immune system against myeloma without causing severe side effects. 

While more research is needed, these findings hint at the potential for trispecific antibodies to become a powerful tool in the fight against myeloma.

Patient Perspective

Doug Keller, a myeloma patient and HealthTree coach, shares his perspective on the subject: 

The title of this article asks the question, "Is there hope for tri-specific antibodies in myeloma care? " The answer is probably! Two studies are discussed here, one of which was successful and the other not. The two tri-specific antibodies studied act in different ways, and these results may lead future research down the more successful path, resulting in new treatments becoming available sooner.

The study that was not successful used an antibody that binds to two T cell targets and showed that excessive stimulation of T cells creates too much toxicity to tolerate, and exhausts T cells quickly. The other antibody, which binds to two B cell targets and one T cell target, was more successful, with little toxicity and good efficacy.

While clinical trial participation is encouraged, patients should be reminded that Phase 1 trials do contain a higher element of risk than later trials and that one should enter these trials with eyes open as to what the risks are.  

You are encouraged to ask questions about these risks prior to enrolling and make sure you are satisfied with the answers.

Continue learning about clinical trials, the different phases, and more through our new multimedia Education Guide.  

Myeloma Clinical Trial Guide: What Endpoints Mean For You

Conclusion

Trispecific antibodies are still in their early stages of development, and while some attempts have been unsuccessful, new therapies like ISB 2001 bring fresh hope. Continued research and patient participation in clinical trials remains essential to unlocking their full potential in multiple myeloma care.

To learn more about trispecific antibodies, watch our HealthTree University video below: