Legend Biotech and its partner Janssen are presenting six abstracts at the ASCO meeting in June detailing ciltacabtagene autoleucel (cilta-cel) CAR-T studies in multiple myeloma.
Ying Huang, Legend Biotech’s CEO and CFO, pictured above. (Legend Biotech)
Legend Biotech and its partner Janssen are presenting six abstracts at the American Society for Clinical Oncology (ASCO) meeting in June detailing ciltacabtagene autoleucel (cilta-cel) CAR-T studies in multiple myeloma.
On May 20, the European Medicines Agency (EMA) accepted the Marketing Authorization Application (MAA) for this therapy, triggering a $15 million milestone payment from Legend’s partner, Janssen.
BioSpace caught up with Ying Huang, Legend Biotech’s CEO and CFO, before the conference to learn more about these studies and how they may benefit patients.
BioSpace: Briefly, what is cilta-cel and how does it work?
Ying Huang: Cilta-cel is an investigational chimeric antigen receptor T (CAR-T)-cell therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. (BCMA is a protein that is highly expressed on myeloma cells.)
CAR‑T therapy is a highly personalized technology where a patient’s own T-cells are re-programmed using genetic engineering to target and eradicate cancer cells. In essence, we are priming the patient’s own immune system to fight cancer. It has the potential to be very effective at treating the disease.
BSp: What’s unique about this therapy?
YH: The progression-free survival (PFS) rate. With cilta-cel, we are seeing progression-free survival of nearly two years. Historical studies showed that typical progression-free survival is 3-4 months in this population. We’re also seeing some unprecedented results in terms of objective response rate (ORR) and stringent complete response (sCR).
BSp: Looking at the cilta-cel studies presented this year at ASCO, what are the key takeaways?
YH: First of all, cilta-cel demonstrates a median progression-free survival (PFS) of 22.8 months with a median 18-month follow-up in the CARTITUDE-1 study. In our view, this is really an exciting result and potentially best-in-class efficacy in the heavily pre-treated patient population.
Secondly, this is the first time we are presenting safety and efficacy of cilta-cel in early lines of multiple myeloma. We are encouraged by the 95% ORR and 75% complete CR in patients who received one to three prior lines of treatment. Therefore, we are excited about the potential for cilta-cel to move into early lines of multiple myeloma and benefit a larger number of patients.
Last but not the least, we are pleased to report the incidence of movement and neurocognitive adverse events decreased from 5% in the CARTITUDE-1 study to less than 1% in CARTITUDE 2 & 4 studies after the implementation of risk mitigation strategies by Legend and Janssen.
Cilta-cel is continuing to provide deep, durable and sustained benefits in patients – even at longer term follow-ups – and with manageable safety profile.
BSp: What was the response rate in heavily-treated patients?
YH: Updated results from the CARTITUDE-1 study show that 98% of heavily pretreated patients responded to treatment, despite receiving a median of six prior treatments (range 3-18). There also was an increasing stringent complete response (sCR) of 80%, up from 67% at the 12 month follow up. The safety profile continues to be manageable and new patient management strategies implemented in the CARTITUDE program were successful in preventing and reducing incidence of neurotoxicity.
BSp: One of the abstracts noted 14 deaths, “of which 5 were due to disease progression, and 4 due to treatment-related serious adverse events (AEs).” What happened?
YH: Among the 14 deaths reported at ASH (where we presented 12-mo. follow up data), 5 were due to progressive diseases, 3 were due to AEs unrelated to treatment (1 pneumonia, 2 AML), and 6 were due to AEs related treatment. The 4 treatment-related AEs were sepsis, lung abscess, respiratory failure, and neurotoxicity.
We have since implemented risk mitigation strategies, including proactive treatment of CRS, enhanced bridging therapy to reduce tumor burden, and aggressive treatment of low-grade neurotoxicity.
BSp: What does Cilta-cel portend for multiple myeloma patients?
YH: Real-world evidence suggests that cilta-cel outperforms currently available therapies for heavily pretreated patients with multiple myeloma.
The CARTITUDE-2 study assessed cilta-cel in patients who had received 1-3 prior lines of therapy and had stopped responding to Revlimid. Results from Cohort A of this study show that cilta-cel led to early and deep responses with a manageable safety profile, including in patients treated in an outpatient setting. It’s worth noting that no Grade 3 neurotoxicity was observed in Cohort A.
BSp: What do these results imply for Legend Biotech?
YH: They set us up well for further exploring the potential of cilta-cel in other cohorts of CARTITUDE-2 and in the ongoing Phase III CARTITUDE-4 study in patients with one to three prior lines of therapy.
These results solidify the leadership position for Legend Biotech in the field of CAR-T treatment. We are continuing to push these trials forward with the hope of providing our patients and the multiple myeloma community with a new paradigm shifting treatment option.
BSp: What’s next for the cilta-cel drug development program?
YH: Our collaboration partner, Janssen, has completed the rolling submission of the Biologics License Application (BLA) to U.S. FDA seeking approval of cilta-cel for the treatment of relapsed and/or refractory multiple myeloma. Janssen and Legend are working closely with health authorities to bring this treatment to market.
Additionally, we have a comprehensive CARTITUDE development program that’s continuing to explore cilta-cel in different groups of patients and different treatment settings. Within it:
- CARTITUDE-2 is a multi-cohort study. We hope to have more data from the various cohorts towards the end of the year.
- CARTITUDE-4 is a Phase III trial. It is open and enrolling very well. This study compares the efficacy of cilta-cel with standard therapy – either PVd or DPd.
- LEGEND-2 is a separate, ongoing single-arm, open-label Phase I study of 74 patients. It is being conducted at four hospitals in China to evaluate the efficacy and safety of cilta-cel to treat relapsed or refractory multiple myeloma.
- CARTIFAN-1 is a Phase II registration-enabling study being conducted in China.
