Legend Biotech and partner Johnson & Johnson just keep rolling out new data on Carvykti. The latest? The closely watched CAR-T therapy sustained an effect in heavily pretreated multiple myeloma patients and shrank tumors when given earlier in a population with otherwise unyielding disease.
After a median follow-up of 27 months, the phase 1b/2 Cartitude-1 study that got Carvykti its FDA nod in late-line multiple myeloma is yet to reach the median time to disease progression or death.
The latest results show that 54.9% of heavily pretreated patients who got a single Carvykti infusion demonstrated no disease progression and 70% were still alive, Marck Wildgust, Ph.D., vice president of oncology global medical affairs at J&J’s Janssen, told Fierce Pharma in an interview. Detailed data will be presented at the 2022 American Society of Clinical Oncology annual meeting.
Cartitude-1 enrolled a myeloma patient group that had received at least three—or a median of six—prior lines of treatment. Historically, the median progression-free survival for this population was just about three to four months, and patients would typically die in about a year, Wildgust said.
For Bristol Myers Squibb’s rival BCMA-targeted CAR-T therapy Abecma, the median progression-free survival in the KarMMa trial of a similarly heavily pretreated population was 8.6 months.
“The fact that we’ve seen a median PFS of well beyond two years and we still haven’t reached it, I think speaks to the efficacy” of Carvykti, Wildgust said.
As Carvykti’s ability in the latter-line setting is well-established, attention has shifted to earlier treatment. Also at ASCO 2022, J&J and Legend will present data in patients who relapsed quickly after initial therapy.
In patients who had received one prior line of therapy and progressed within 12 months, Carvykti shrank tumors in all 19 patients and helped 90% of them reach complete response or better.
The data come from cohort B of the phase 2 Cartitutde-2 trial after 13.4 months of median follow-up. Both data points showed improvement from an earlier analysis of 18 patients after a median 4.7 months of follow-up. Back then, the overall response rate was 88.9%, and 27.8% of patients had complete response or stringent complete response.
J&J and Legend previously reported data from cohort A, which enrolled patients who had progressive disease after one to three prior lines of therapy and were refractory to BMS’ Revlimid. There, Carvykti triggered a response in 95% of 20 patients after a median follow-up of 9.7 months. The rate of complete response hit 85%, according to data presented at the American Society of Hematology 2021 annual meeting last December.
Wildgust suggested the cohort B population is at higher risk because they didn’t even respond well to first-line therapy. But throughout the two Cartitude-2 cohorts and the Cartitude-1 trial, Carvykti has shown consistent results with high response rates and deep tumor clearance lasting for a long time, Wildgust said.
J&J and Legend are now testing the cohort A population in a larger phase 3 trial coded Cartitude-4, targeting a potential second-line approval. But it doesn’t have a phase 3 planned for a similar population as cohort B.
J&J also launched the phase 3 Cartitude-5 study for newly diagnosed myeloma patients who are not suitable for stem cell transplant. Its CAR-T will be tested following a combo of Takeda’s Velcade, BMS’ Revlimid and dexamethasone. It also has Cartitude-6, where J&J aims to find if Carvykti can replace stem cell transplants in eligible newly diagnosed patients.
“We’ve taken a different point of view and said […] let’s treat those patients who are treatment-naïve,” Widgust said. “I think we’re saying let’s go right to the newly diagnosed setting.”