Janssen’s BCMA-targeting CAR-T therapy eliminated tumors in 69% of patients with advanced multiple myeloma in a small phase 1 study. The treatment, which also shrank tumors in all 29 of the patients, is moving forward into a phase 2 study due to read out by the end of 2020.
The study, presented Saturday at the annual meeting of the American Society of Hematology, also found that six months after dosing, the treatment, JNJ-4528, kept cancer at bay in 27 of the 29 patients, or 93%.
The trial was small and focused on gauging safety and picking a dose for phase 2, but the efficacy results are encouraging, especially in a patient group that has “essentially run out of treatment options,” Mark Wildgust, Ph.D., vice president of global medical affairs, oncology, at Janssen R&D, told FierceBiotech.
It involved patients with relapsed or refractory multiple myeloma, meaning prior treatments did not affect their cancer, or their cancer came back after treatment. Before starting the trial, all of the patients saw their cancer worsen within one year after their most recent treatment and they had tried at least three types of therapies, including a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 antibody.
“That means all of them have seen the three different classes of drugs … Not only were all of them triple-exposed, but 86% of them were triple-refractory—they had basically failed on those therapies,” Wildgust said. And nearly one-third of patients had no luck despite having tried five different drugs.
“There’s not too much left for these patients,” he said.
With time, the treatment could prove even more effective as some of the patients whose tumors were eradicated—who had complete responses, in oncology-speak—didn't get there right away. Patients took a median of one month to get to complete response in this study, but some patients took as long as nine months to get there, he said.
“Some patients with a partial response or very good partial response at six months can switch to a complete response,” Wildgust said. “There is a potential for the complete response rate to go up; we need to continue to follow it and see how it goes.”
The most common side effects of the treatment were cytokine release syndrome (CRS), which happens when CAR-T works too well and activates the immune system too strongly, and neutropenia, an abnormally low white blood cell count. Even though 93% of the patients experienced CRS, the majority of cases, 86%, were grade 1 or 2, requiring only moderate treatment or treatment to address symptoms like headache and fatigue. One patient needed aggressive treatment for CRS, and one patient died from the condition.
JNJ-4528 is “essentially the same CAR-T" as the one that Janssen partner Legend Biotech is developing in China—“with a little tweak in manufacturing between China and what we do here in the U.S.,” Wildgust said. So, while not much can be extrapolated from the phase 1 study, its data can be weighed alongside data from Legend’s phase 2 program in China.
“We can kind of look toward the LEGEND-2 data and that perhaps gives you a window of what we might see,” Wildgust said. “In particular, those patients getting complete responses tell us those patients are doing the very best.”
Legend will present follow-up data for that program Monday showing the treatment, known as LCAR-B38M in China, shrank tumors in 88% of patients and eliminated them in 74% of patients. A year and a half after dosing, the treatment kept cancer at bay in 50% of all patients but in 71% of patients who had achieved a complete response and whose disease was undetectable after treatment.
Janssen has fully enrolled the phase 2 part of this study and plans to report data by the end of 2020. It hopes to present a full data set and file JNJ-4258 for regulatory approval in the second half of next year, Wildgust said. The company has not disclosed how many patients it enrolled in the phase 2 study.
It could be even better than Janssen’s own multiple myeloma drug, Darzalex (daratumumab), an anti-CD38 antibody.
“We were excited about a 30% response rate in daratumumab. This patient population is more refractory than the original daratumumab studies and every patient had a clinical response. While it’s a small group of patients, it is very promising to see 100% of patients with a clinical response,” Wildgust said.