At this year’s virtual annual American Society of Clinical Oncology conference (ASCO 2021) on 4-8 June, results from the Phase II ZUMA-3 study for Gilead’s Tecartus (KTE-X19) were presented. Adult patients with relapsed or refractory (R/R) acute lymphocytic leukaemia (ALL) received a Tecartus infusion and were assessed for complete remission or complete remission with incomplete hematologic recovery (CR/CRi) as the primary endpoint.
Adult R/R ALL patients are typically managed with Amgen‘s CD19/CD3 bispecific antibody Blincyto (blinatumomab) or Pfizer’s anti-CD22 antibody-drug conjugate Besponsa (inotuzumab ozogamicin). Novartis’ CAR-T cell product, Kymriah, is primarily aimed at paediatric R/R patients, with its label specifying use in patients up to 25 years of age, but is sometimes used off-label in young adult patients older than 25. Older adults, therefore, have no access to a CAR-T cell product that could offer long-term remission with a single treatment, instead of a stem cell transplant.
In ZUMA-3, out of 55 evaluable patients, 70.9% presented with a CR/CRi, meeting the primary endpoint. For all patients, the median duration of response was 12.8 months and the median overall survival (OS) was 18.2 months. In the subgroup that achieved CR/CRi, median OS was not reached, demonstrating durable benefit after a single cell infusion. Adverse events (AEs) typical to CAR-T cells include cytokine release syndrome (CRS) and neurologic events. CRS of any grade was observed in 89% of patients, with 24% of patients having grade ≥3. Neurologic events appeared in 60% of patients, with 25% of patients having Grade ≥3. Tecartus was successfully manufactured for 92% of patients, which is on par with other CAR-T cell products.
Among the CD19 CAR-T players, efficacy data are similar to data from Kymriah’s ELIANA pivotal trial and Autolus Therapeutics’ AUTO-1 early data from the ALLCAR trial, but safety data lag behind. In the soon-to-be very competitive space of CAR-T cell options for adult R/R ALL, any clinical attribute can tip the scale in a product’s favour. AUTO-1 has promised a very favourable AE profile that may well give it the upper hand, despite a delayed entry expected in 2023. Kymriah’s first-mover advantage and AUTO-1’s anticipated better AE profile are, therefore, expected to have a negative impact on Tecartus’ future uptake.
Tecartus was approved by the US Food and Drug Administration (FDA) for adult patients with R/R mantle cell lymphoma last June. With a supplemental biologics license application (sBLA) for ALL submitted to the FDA this April, Tecartus could be available in the US market in the fourth quarter of this year, given its breakthrough therapy and orphan drug designations. In ZUMA-3, 78% of patients received more than two prior lines of therapy, making an FDA label likely to be given for the third line of therapy. GlobalData forecasts Tecartus to reach peak sales of $110m in ALL worldwide by 2029.