ZUMA-1
A Phase 1/2 Multicenter Study Evaluating the Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma
Phase 1/2N = 111NCT02348216
- Population
- Adults with refractory large B-cell lymphoma (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma or transformed follicular lymphoma) whose disease was refractory despite recommended prior therapy.
- Design
- Multicentre, single-arm study. The phase 2 report enrolled 111 patients; axicabtagene ciloleucel (axi-cel) was successfully manufactured for 110 and administered to 101 after conditioning with low-dose cyclophosphamide and fludarabine, at a target dose of 2 million anti-CD19 CAR T cells per kilogram. Primary end point: objective response rate (complete plus partial response). ClinicalTrials.gov lists 307 enrolled across the whole registered study.
- Primary endpoint
- ORR
- Arms
- Axicabtagene ciloleucel (experimental, n = 101): Single infusion of autologous anti-CD19 CAR T cells after low-dose cyclophosphamide and fludarabine conditioning
- People
- Neelapu SS, senior author Go WY
Show the numbers
| Endpoint | Analysis | Axicabtagene ciloleucel | Control | Effect |
|---|---|---|---|---|
| ORRPhase 2 patients who received axi-cel (101 of 111 enrolled; the modified intention-to-treat population in the full text)Objective response rate: combined complete and partial response rates (stated primary end point). | primarymedian follow-up 8.7 monthsNeelapu 2017 | 82% (73–89%) | — | Primary-analysis response rate in the 101 treated patients (data cut-off 27 January 2017, median follow-up 8.7 months in the full text). In the prespecified primary analysis of the first 92 patients the rate was also 82% (95% CI 72 to 89; P<0.001 against a 20% historical control rate). The abstract's median follow-up of 15.4 months belongs to the updated analysis (data cut-off 11 August 2017), in which 42% of patients remained in response and 40% in complete response. |
| CR ratePhase 2 patients who received axi-cel (101 of 111 enrolled; the modified intention-to-treat population in the full text) | primarymedian follow-up 8.7 monthsNeelapu 2017 | 54% | — | Primary analysis in the 101 treated patients; in the first 92 patients the complete response rate was 52%. The updated analysis of the 108 patients treated in phases 1 and 2 reported a complete response rate of 58%. |
| OSUpdated analysis: the 108 patients treated in the phase 1 and phase 2 parts (Figure 2C legend of the full text) | long term-updatemedian follow-up 15.4 monthsNeelapu 2017 | 52% at 18 mo (41–62%) | — | Overall survival rate at 18 months, a secondary end point, from the updated analysis (data cut-off 11 August 2017); median overall survival was not reached. In that analysis 42% of patients remained in response and 40% in complete response. |
| ORRTreated patients (101)Investigator-assessed objective response in treated patients. | long term-updatemedian follow-up 63.1 monthsNeelapu 2023 | 83% | — | Complete response rate 58%; responses were ongoing in 31% of patients at data cut-off. |
| OSTreated patients (101) | long term-updatemedian follow-up 63.1 monthsNeelapu 2023 | median 25.8 months; 42.6% at 5 y | — | Estimated 5-year OS rate 42.6%. Disease-specific survival (excluding deaths unrelated to progression) estimated at 5 years was 51.0%. |
| Endpoint | Analysis | Axicabtagene ciloleucel | Control | Effect |
|---|---|---|---|---|
| ORRPhase 2 patients who received axi-cel (101 of 111 enrolled; the modified intention-to-treat population in the full text)Objective response rate: combined complete and partial response rates (stated primary end point). | primarymedian follow-up 8.7 monthsNeelapu 2017 | 82% (73–89%) | — | Primary-analysis response rate in the 101 treated patients (data cut-off 27 January 2017, median follow-up 8.7 months in the full text). In the prespecified primary analysis of the first 92 patients the rate was also 82% (95% CI 72 to 89; P<0.001 against a 20% historical control rate). The abstract's median follow-up of 15.4 months belongs to the updated analysis (data cut-off 11 August 2017), in which 42% of patients remained in response and 40% in complete response. |
| CR ratePhase 2 patients who received axi-cel (101 of 111 enrolled; the modified intention-to-treat population in the full text) | primarymedian follow-up 8.7 monthsNeelapu 2017 | 54% | — | Primary analysis in the 101 treated patients; in the first 92 patients the complete response rate was 52%. The updated analysis of the 108 patients treated in phases 1 and 2 reported a complete response rate of 58%. |
| OSUpdated analysis: the 108 patients treated in the phase 1 and phase 2 parts (Figure 2C legend of the full text) | long term-updatemedian follow-up 15.4 monthsNeelapu 2017 | 52% at 18 mo (41–62%) | — | Overall survival rate at 18 months, a secondary end point, from the updated analysis (data cut-off 11 August 2017); median overall survival was not reached. In that analysis 42% of patients remained in response and 40% in complete response. |
| ORRTreated patients (101)Investigator-assessed objective response in treated patients. | long term-updatemedian follow-up 63.1 monthsNeelapu 2023 | 83% | — | Complete response rate 58%; responses were ongoing in 31% of patients at data cut-off. |
| OSTreated patients (101) | long term-updatemedian follow-up 63.1 monthsNeelapu 2023 | median 25.8 months; 42.6% at 5 y | — | Estimated 5-year OS rate 42.6%. Disease-specific survival (excluding deaths unrelated to progression) estimated at 5 years was 51.0%. |
- Axicabtagene ciloleucel (experimental)
Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.
Data table (modelled values)
| Months | Axicabtagene ciloleucel |
|---|---|
| 0 | 100.0% |
| 16 | 65.1% |
| 32 | 42.3% |
| 48 | 27.5% |
| 65 | 17.4% |
Appears in
Sources
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017;377(26):2531-2544.
Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, et al. Five-Year Follow-Up Supports Curative Potential of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma (ZUMA-1). Blood. 2023;141(19):2307-2315.