First Patient Enrolled in Horizon Two Clinical Trial to Reimagine How High-Risk, Newly Diagnosed Multiple Myeloma Is Treated

Horizon Two extends innovative clinical trial program to patients with some of greatest unmet need in myeloma.

Today, the Multiple Myeloma Research Foundation® (MMRF®) announced that the first patient has been enrolled in the groundbreaking Horizon Two clinical trial that aims to identify the best treatments and treatment combinations for patients with high-risk, newly diagnosed multiple myeloma. This is the only multicenter clinical trial for high-risk newly diagnosed myeloma in the U.S.

Over the last 25 years, we’ve made incredible progress treating standard-risk multiple myeloma—to the point that a very small number of patients are now considered cured. But the estimated 20 percent of patients who have high-risk disease haven’t seen the same benefits. They relapse quickly and cycle through standard therapies faster.

“Horizon Two represents the next leap forward in the Horizon Clinical Trials Program—bringing the same innovative platform design to a population that urgently needs better options,” said the MMRF’s President and CEO Michael Andreini. “Progress for high-risk patients has been too slow and the options too few. This trial is built to change that by rigorously testing the combinations and strategies that are most likely to change their outcomes.”

Horizon Two is designed to answer questions that matter most to high-risk patients—and that no one else is pursuing. Investigators will study what therapies and combinations have the maximum benefit and whether patients can safely stop treatment altogether after a sustained period of negative minimal residual disease (MRD).

The trial is conducted by the MMRF’s clinical research subsidiary: the Multiple Myeloma Research Consortium^® (MMRC^®), a collaborative network of leading academic medical centers and community-based clinics across the U.S.

Unlike traditional clinical trials that test one treatment at a time, the MMRC Horizon Clinical Trials program uses an innovative adaptive platform that’s bult for speed. Its design allows investigators to test multiple treatments (also called “arms”) at the same time and to open arms more quickly than other trials can. The result: New insights and data about the most effective therapies and combinations on a faster timeline.

“High-risk myeloma is a small enough population that no single site could run this trial alone. It requires a large, coordinated network and a leader willing to prioritize patient need. The MMRF is that leader,” said Horizon investigator Dr. Sham Mailankody of Memorial Sloan Kettering (MSK) Cancer Center. “By uniting sites across the country under one innovative platform, we can finally pursue the questions that matter most to these patients.”

Horizon Two is currently enrolling an experimental arm and a control arm, comparing a novel drug combination with a BCMA-directed bispecific antibody as a first-line treatment against a standard regimen. Patients in each of these arms who achieve MRD-negativity will be allowed to discontinue treatment after three years of maintenance therapy.

The novel combination includes Lynozyfic® (linvoseltamab-gcpt, manufactured by Regeneron), Kyprolis® (carfilzomib, manufactured by Amgen), Revlimid® (lenalidomide, manufactured by Celgene Corporation), and dexamethasone, followed by high-dose therapy (HDT) with autologous stem cell transplant (ASCT). Patients will then receive Lynozyfic-based consolidation and maintenance treatment.

The standard drug regimen involves Sarclisa® (isatuximab-irfc, manufactured by Sanofi), Kyprolis® (carfilzomib), Revlimid® (lenalidomide), and dexamethasone, HDT-ASCT, consolidation, and maintenance.

Additional investigational arms are planned.

“We don’t yet have consensus on the best way to treat high-risk, newly diagnosed patients—making this one of the most challenging areas in myeloma. But Horizon Two is designed to change that,” said MMRF Chief Medical Officer Hearn Jay Cho, MD, PhD. “This BCMA-directed bispecific antibody has already proven very effective in relapsed/refractory patients. By investigating it as a first-line treatment for high-risk myeloma, we’ll generate critical evidence that physicians and patients need to make informed decisions.”

The MMRC’s broad, diverse, and collaborative network ensures that Horizon investigators can enroll more patients and that the trial’s population is far more representative of the disease. In fact, the Horizon One clinical trial focused on optimizing treatment for relapsed/refractory myeloma has so far enrolled more Black patients and patients over the age of 71 than other myeloma trials—two groups that have been historically underrepresented in research.

As with other landmark MMRC-led studies, Horizon investigators will collect blood and bone marrow samples to gather vast amounts of clinical and laboratory data. This will deliver new insights on how and why patients respond to therapies, thereby laying a foundation for more personalized care for this patient population with high unmet need.

“Patients with high-risk myeloma can’t afford to wait years for the field to catch up,” Andreini said. “That urgency drives everything we do at the MMRF. Horizon Two is our commitment to these patients made concrete: the best science, the broadest possible patient population, and a platform designed to get answers faster than anyone thought possible.”

For more information on Horizon Two, visit our website or clinicaltrials.gov.