Novartis on Wednesday released interim results from a Phase II trial showing that the experimental CAR-T treatment CTL019, also known as tisagenlecleucel, demonstrated a three-month overall response rate (ORR) of 45 percent, with 37 percent achieving a complete response and 8 percent achieving a partial response, in adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The data, which come from the JULIET study, will be presented at the International Conference on Malignant Lymphoma (ICML) meeting later this month.
Chief medical officer Vas Narasimhan remarked "we are pleased the interim results...highlight the potential for CTL019 to elicit durable responses in patients with relapsed/refractory DLBCL, an area of high unmet need." Narasimhan added "when you look across the three competitors' data sets, they're all in a similar range of responses," continuing "what's critical is to see the data sets fully mature... and look at the overall safety profile."
The study consisted of adults with relapsed or refractory DLBCL who received at least two prior lines of chemotherapy and who experienced disease progression or were ineligible for autologous stem cell transplant. The primary endpoint of the trial was best ORR, defined as complete responses plus partial responses, as determined by a central review performed by an independent review committee, while secondary goals included overall survival, duration of response and progression-free survival.
Novartis noted that among the 51 patients with at least three months of follow-up or earlier discontinuation, the best ORR was 59 percent, including complete and partial response rates of 43 percent and 16 percent, respectively. The drugmaker cautioned that 43 patients exited the study prior to infusion, with most withdrawing due to rapid disease progression or deterioration in their clinical status, while nine of 141 enrolled patients could not be infused because of an inability to manufacture an adequate dose of CAR-T cells.
Shares in Kite Pharma, which was granted priority review by the FDA last month for its investigational CAR-T therapy axicabtagene ciloleucel in the treatment of non-Hodgkin lymphoma (NHL), jumped as much as 6.1 percent on the news. Commenting on the findings, Cowen analyst Eric Schmidt remarked "an abstract from the [ICML meeting] suggests (1) efficacy data in the treated population may be on par with those from Kite's ZUMA-1 trial and (2) Novartis is having significant issues with manufacturing." Schmidt continued "unless these issues can be remedied, we do not view CTL019 as competitive."
Meanwhile, Juno Therapeutics ended development of the investigational CAR-T therapy JCAR015 for the treatment of adults with relapsed or refractory acute lymphoblastic leukaemia (ALL) following safety issues including five patient deaths. Earlier this week, the drugmaker unveiled early-stage study data for JCAR017 illustrating the efficacy of the treatment in patients with aggressive relapsed or refractory NHL (for related analysis, see ViewPoints: CAR-T musings – Kite doesn't disappoint while Juno tacks on another patient death).
Novartis was previously awarded breakthrough therapy designation by the FDA for CTL019 in the treatment of adults with relapsed or refractory DLBCL. The therapy has also been granted breakthrough therapy designation and priority review in the US for use in children and adults with relapsed/refractory ALL.
The Swiss drugmaker said that the full primary analysis of the JULIET study, which will be released later this year, will support regulatory submissions in the US and EU.
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