Johnson & Johnson has seen response rates as high as 97% in multiple myeloma before but this time, it’s not for Carvykti, which is making headlines of its own at the American Society of Clinical Oncology annual meeting in Chicago.
No, this time the healthcare giant’s pharmaceutical unit Janssen is shining the spotlight on an early-stage combo study for talquetamab and Tecvayli in relapsed or refractory multiple myeloma. The combo immunotherapy regimen, which is designed to target antigens on myeloma cells, demonstrated an overall response rate (ORR) of 86.6% (71 of 82 patients) across all dose levels. The data also reveal an ORR of 96.3% (26 of 27 patients) for individuals receiving the recommended phase 2 regimen.
“There's only one drug that's ever got better than 96%—that’s cilta-cel and that's like 97%,” said Mark Wildgust, Ph.D., Janssen’s vice president of Oncology Global Medical Affairs, on the sidelines of the conference, referring to Carvykti.
The new phase 1b data from a trial called RedirecTT-1 presented at ASCO provides a look at both treatments together, whereas previously Janssen has showcased each alone. Bispecific antibody Tecvayli received accelerated approval in October 2022 for patients with relapsed or refractory multiple myeloma, while Janssen just submitted a new drug application for talquetamab in December 2022.
Wildgust said this is some of the first clinical data ever shared for a dual combo of two bispecifics in relapsed or refractory multiple myeloma. Talquetamab achieved an ORR of 74.1% alone when administered weekly, while Tecvayli was granted the approval based on an ORR of 61.8%.
“To have 26 of 27 patients responding—it's really, really remarkable,” Wildgust said of the combo data for the recommended dose group. He noted the heavily pretreated population also included those with extramedullary disease. EMD is a condition that occurs when myeloma cells form tumors in soft tissues and organs instead of in the bone marrow. For the seven EMD patients in the recommended dose group, there was an ORR of 85.7%.
“Those are some of the hardest to treat patients,” Wildgust explained, adding that response rates among EMD patients—even for Tecvayli or talquetamab by themselves—typically sits in the 30% to 40% range. He called the 86% response rate "extremely promising.” The new data has prompted J&J to look at an expansion cohort for patients with EMD, according to Wildgust.
When looking at the new data, all patients had a median progression-free survival (PFS) of 20.9 months.
As for the safety profile, Wildgust said the combo was well tolerated and consistent with what has been observed with each drug given as a monotherapy. The most common hematologic adverse event (AE) reported was neutropenia—a low count of certain white blood cells—occurring in 65.6% of patients across all dose levels, with 61% classified as grade 3 or 4 events. Neutropenia occurred in 55% of patients in the recommended dose cohort, with 44% of the events grade 3 or 4. Adverse events are rated from grade 1 through 5, with 5 being a fatal event, 4 being a life-threatening event and 3 being one that is severe but not immediately life-threatening.
Nearly all the patients had one or more treatment-emergent adverse event (TEAE). These events were observed in 96.8% (90/93) of the overall study population and 94.1% (32/34) of patients receiving recommended dosing.
The high TEAEs appeared not to significantly impact discontinuation rates, with only 6.5% ending treatment due to adverse events. There were six TEAE-related deaths (6.5%) among all patients, with one occurring in the recommended dose group. At data cutoff, 61% (57/93) of all patients remained on either Tecvayli or talquetamab.
The low discontinuation rates despite high TEAEs could have something to do with the nature of the disease. The incurable condition is the third most common blood cancer, with an estimated 35,000 Americans expected to be diagnosed this year and more than 12,000 people expected to die from it.
Talquetamab received orphan drug designation from the FDA in 2021, followed by a breakthrough therapy designation last summer for adult patients with relapsed or refractory multiple myeloma who have previously received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.
J&J also reported more data on the bispecific T-cell engaging antibody at ASCO, following up data shared earlier this year.
Elsewhere at the conference, J&J showed off Carvykti, the Legend Biotech-partnered personalized cell therapy, after a recent data leak revealed a dramatic benefit for earlier line treatment in multiple myeloma. In a small group of heavily pretreated patients with multiple myeloma that was refractory to three classes of therapies, Carvykti reduced the risk of cancer progression or death by 85% compared with physician’s choice of standard combo treatment.
The results beat Bristol Myers Squibb’s rival CAR-T therapy Abecma, which achieved 54% on the same measure in a similar population.
With Carvykti and talquetamab and Tecvayli, Janssen is looking to put down a marker in multiple myeloma.