JNJ-4528 Continues to Show Strong, Durable Responses in Trial

Janssen’s investigational CAR T-cell therapy for multiple myeloma, called JNJ-4528, continues to lead to strong and durable responses in all patients with relapsed or refractory disease who are participating in a Phase 1b/2 trial.

These findings were announced in an oral presentation, “Update of CARTITUDE-1: A phase Ib/II study of JNJ-4528, a B-cell maturation antigen (BCMA)-directed CAR-T-cell therapy, in relapsed/refractory multiple myeloma,” at the recent 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program, held online.

Known as LCAR-B38M in China, JNJ-4528 is a form of immunotherapy in which a person’s own T-cells — immune cells with anti-cancer activity — are collected and engineered in the lab to better recognize and eliminate cancer cells. The modified cells are expanded to millions and then returned to the patient.

JNJ-4528 is made of modified T-cells that specifically identify and eliminate malignant cancer cells containing the B-cell mature antigen (BCMA) — a protein found on the surface of myeloma cells that is considered one of the best targets for this therapy.

It is being investigated in the CARTITUDE-1 Phase 1b/2 trial (NCT03548207), which is ongoing at several clinical sites across the U.S. and Japan. Recruitment is still underway in the Japanese sites.

The trial is enrolling an estimated 118 adults, ages 18 and older, with relapsed or refractory myeloma. Participants will have received at least three prior lines of therapy — including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 antibody — or failed to respond to treatment with a PI and an IMiD, and had their disease progress within a year of their last treatment.

During its initial Phase 1b part, the study will assess the treatment’s safety and determine the best dose at which JNJ-4528 should be administered to patients. The dosing is based on previous data from the therapy’s first-in-human LEGEND-2 Phase 1/2 trial (NCT03090659).

This will be followed by a Phase 2 part, which will focus on assessing the efficacy of the optimal dose selected during the initial portion of the study.

Top-line data from the first part of CARTITUDE-1, announced last year, showed that at a median dose of 0.73 million CAR T-cells per kilogram, JNJ-4528 led to early and deep responses in all 29 patients participating in the study up to that point.

At a median follow-up of six months, all participants had responded to the treatment, with more than half (69%) attaining complete responses or better, and nearly all (89%) achieving very good partial responses or better. Of note, a complete response is the eradication of the disease, while a partial response refers to a partial elimination of the cancer.

The treatment also was found to have a manageable safety profile, with a quarter of the participants experiencing severe, life-threatening, or fatal adverse events.

New data now being announced by Janssen showed that at a median follow-up of 11.5 months, all 29 patients treated in the first part of CARTITUDE-1 continue to show deep and durable responses to the treatment.

A total of 97% of the participants attained very good partial responses or better, and 86% stringent complete responses after receiving a low dose (median of 0.72 million CAR T-cells per kilogram) of JNJ-4528 within approximately a year.

Nearly all (86%) of the individuals were alive and continued showing no signs of disease progression after a period of nine months.

Additionally, most patients (81%) attained a status of minimal residual disease (MRD) negativity —defined as having less than one malignant cancer cell among 10,000 white blood cells — by the time they were first suspected to have achieved a complete response. The median time to first response was one month.

Individuals who responded to treatment with JNJ-4528 had received a median of five prior lines of therapy, with some of them having received up to 18 treatment regimens. Nearly all of them (86%) had failed to respond to three prior treatment regimens, and approximately a third (28%) to five.

“The longer-term results for JNJ-4528, as demonstrated through the latest findings from the CARTITUDE-1 study, show the continued treatment effect for heavily pretreated patients who faced a dismal prognosis,” Jesus G Berdeja, MD, director of myeloma research at the Sarah Cannon Research Institute, and principal investigator of the trial, said in a press release.

“We’re encouraged by not only the relatively high rate of stringent complete responses, but also the progression-free survival seen in these patients,” Berdeja added.

The most common adverse events reported in the study included low white blood cell counts (100%) and cytokine release syndrome, known as CRS (93%). CRS developed within 2-12 days after treatment infusion, and was only mild or moderate in most cases.

Of note, CRS is a serious complication of certain types of immunotherapy. It is caused by large amounts of cytokines — molecules that mediate the immune response — being released by modified T-cells, leading to an overactive immune system.

Three patients died during the first portion of the trial: one from CRS, another from acute myeloid leukemia, and one from progressive disease.

“These recently updated data from the CARTITUDE-1 study suggest a durable response and tolerable safety profile for JNJ-4528,” said Sen Zhuang, MD, PhD, vice president of oncology clinical development at Janssen.

“We continue to advance the investigation of this novel CAR-T treatment with the goal of bringing a differentiated immunotherapy to patients with multiple myeloma, many of whom have exhausted all potential prior treatment options,” Zhuang said.