Janssen’s investigational CAR T-cell therapy for multiple myeloma, called JNJ-4528 (JNJ-68284528), safely led to early and deep responses in all patients with relapsed or refractory multiple myeloma treated in the first part of a Phase 1/2 trial.
These findings were announced in the oral presentation, “Results from CARTITUDE-1: A Phase 1b/2 Study of JNJ-4528, a CAR-T Cell Therapy Directed Against B-Cell Maturation Antigen (BCMA), in Patients with Relapsed and/or Refractory Multiple Myeloma (R/R MM),” at the American Society of Hematology (ASH) 2019 Annual Meeting in Orlando, Florida.
Chimeric antigen receptor T-cell therapy, more commonly known as CAR T-cell therapy, is a type of immunotherapy in which a patient’s T-cells — immune cells with anti-cancer activity — are collected and re-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 are genetically-modified human T-cells that specifically recognize 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 — in people with multiple myeloma, while leaving healthy cells unharmed.
The safety and efficacy of JNJ-4528 in adults with relapsed or refractory multiple myeloma is currently being investigated in the CARTITUDE-1 Phase 1b/2 trial (NCT03548207), underway across the U.S. and in Japan.
CARTITUDE enrolled people who either had 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 whose disease progressed within a year of their last treatment.
Top-line data from the first part of CARTITUDE-1 showed that JNJ-4528 (median dose of 0.73 million CAR T-cells per kilogram) led to early and deep responses in the 29 patients treated in the study so far. These patients had received a median of five prior lines of therapy, with some having received as many as 18 lines.
At a median follow-up of six months, all had responded to treatment, with 69% achieving a complete response or better, and 89% attaining a very good partial response or better. Complete responses refer to total cancer eradication, while partial responses reflect a significant decrease in disease burden, with no signs of cancer spreading. A very good partial response is a stronger type of a partial response.
Twenty-eight days after being infused with JNJ-4528, all evaluable patients achieved a state of minimal residual disease (MRD) negativity, meaning less than one malignant cancer cell was found among 10,000 white blood cells.
In addition, after six months, 27 out of the 29 patients infused with JNJ-4528 continued to show no signs of disease worsening.
JNJ-4528 had a manageable safety profile. The most common adverse events reported during CARTITUDE-1 included cytokine release syndrome (CRS) (93%); low white blood cell counts (93%); anemia (86%); and low platelet counts (86%).
Of note, CRS is a serious side effect that can be triggered by certain immunotherapies, including CAR T-cells. CRS — whose symptoms can include fever, nausea, low blood pressure, and trouble breathing — 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.
Only a quarter of the participants experienced severe (grade 3), life-threatening (grade 4) or fatal (grade 5) adverse events. One patient died of complications from grade 5 CRS.
Based on data from this study’s first part, an optimal JNJ-4528 dose of 0.75 million cells per kilogram will be used during its second, or Phase 2, part.
“These initial results from the Phase 1b portion of the CARTITUDE-1 study highlight a compelling clinical profile for JNJ-4528 in heavily pre-treated patients with relapsed or refractory multiple myeloma,” Deepu Madduri, MD, an assistant professor at the Tisch Cancer Institute at Mount Sinai, and principal study investigator, said in a press release.
“With the CARTITUDE-1 expansion cohort fully enrolled and all patients dosed, we look forward to collecting additional efficacy and safety data to further define the profile of this BCMA-targeted CART therapy,” Madduri said.
CARTITUDE-1’s findings to date are consistent with data from the LEGEND-2 Phase 1/2 study (NCT03090659), the first-in-human trial of LCAR-B38M, the name given this same investigational CAR T-cell therapy in China.
Follow-up data from LEGEND-2 was presented in an oral presentation at the ASH meeting, and showed that LCAR-B38M was safe and led to long-term treatment responses.
After a median follow-up of 19 months, 88% of the patients had responded to treatment, with 74% achieving a complete response. Among those with complete responses, 93% reached a state of MRD negativity.
Nearly half of all infused patients (46%) continued with no signs of disease progression at the median 19-month follow-up.
The median time that treated patients lived without showing any signs of disease worsening (progression-free survival, or PFS) was 20 months. For those who achieved a state of MRD negativity, PFS was 28 months.
“We are encouraged by the overall response reported in patients receiving JNJ-4528, results that build upon the LEGEND-2 study data as reported in Chinese patients and now show promise in U.S. patients,” said Sen Zhuang, MD, PhD, vice president of Oncology Clinical Development at Janssen.
“We are committed to advancing this novel BCMA-targeted CAR-T therapy through clinical development and bringing this immunotherapy to patients who are still in need of effective therapies to rapidly control their disease,” Zhuang added.
JNJ-4528 has been designated an orphan drug from the U.S. Food and Drug Administration (FDA) and given PRIME (PRIority MEdicines) status by the European Medicines Agency (EMA). More recently, based on data from CARTITUDE-1, the FDA decided to designate JNJ-4528 a breakthrough therapy as well.