2L TRANSFORM trial

A Phase 3, randomized, open-label, multicenter,
pivotal trial (N=184)1

TRANSFORM trial evaluated Breyanzi®
head-to-head vs standard therapy in 2L LBCL patients who were R/R ≤ 12 months and potential candidates for transplant1

Standard therapy in the TRANSFORM trial was chemoimmunotherapy followed by high-dose therapy + SCT1
Primary endpoint: EFS (evaluated at 6.2 months)2
Median follow-up at primary analysis was 17.5 months.5
Select secondary endpoints (evaluated at primary analysis): CR rate, PFS, ORR, and DoCR2
Median follow-up at interim analysis was 6.2 months.4
Bridging therapy prior to receiving Breyanzi was optional and patients in the standard therapy arm were allowed to cross over to the Breyanzi arm.2
Patients receiving standard therapy were allowed to receive Breyanzi if they failed to achieve CR or PR after 3 cycles of salvage immunochemotherapy, or had disease progression at any time, or if the patient needed to start a new treatment due to efficacy concerns.2
Over 4x improvement in mEFS over standard therapy in patients who were R/R ≤12 months1*
At 6.2 months median follow-up, mEFS was 10.1 months for Breyanzi vs 2.3 months for standard therapy1
  • 66% reduction in risk of EFS events; HR: 0.34, 95% CI (0.22, 0.52)1†
  • P<0.00011‡
At 17.5 months (median) follow-up, mEFS was not reached in patients who received Breyanzi5
  • Breyanzi mEFS: NR, 95% CI: (9.5, NR)
  • Standard therapy mEFS: 2.4 months, 95% CI: (2.2, 4.9)
Graph showing 4x improvement in mEFS over standard therapy.
Graph showing 4x improvement in mEFS over standard therapy.

Number of subjects at risk
Months BREYANZI Standard therapy
0 92 92
1 87 66
2 76 39
3 62 32
4 59 27
5 55 22
6 52 19
7 48 19
8 45 19
9 24 12
10 20 12
11 17 10
12 5 3
13 3 2
14 3 2
15 3 2
16 3 2
17 0 0
Symbols represent censored observations.
EFS is defined as the time of randomization to death from any cause, progressive disease, failure to achieve CR or PR by 9 weeks post-randomization, or start of new lymphoma therapy due to efficacy concerns, whichever occurs first.1
Median PFS was not reached at 17.5 months median follow-up5*
  • Breyanzi mPFS: NR, 95% CI: (12.6, NR); HR: 0.40, 95% CI: (0.26, 0.62)
  • Standard therapy mPFS: 6.2 months, 95% CI: (4.3, 8.6)
  • P<0.0001§
Graph showing PFS 2x that of standard therapy
Graph showing PFS 2x that of standard therapy

Number of subjects at risk
Months BREYANZI Standard therapy
0 92 92
1 88 66
2 79 42
3 63 33
4 60 27
5 56 22
6 53 19
7 49 19
8 46 19
9 25 12
10 21 12
11 18 10
12 6 3
13 3 2
14 3 2
15 3 2
16 3 2
17 0 0
Symbols represent censored observations. Interim 6.2-month median follow-up: 14.8 months for Breyanzi vs 5.7 months for standard therapy. PFS is defined as the time from randomization to progressive disease or death from any cause, whichever
occurs first.2
Overall survival of patients treated with Breyanzi vs standard therapy5
73% of Breyanzi patients and 61% of standard therapy patients were alive at time of 18-month follow-up
  • Breyanzi mOS: NR, 95% CI: (29.5, NR); HR: 0.72, 95% CI: (0.44, 1.18)
  • Standard therapy mOS: 29.9 months, 95% CI: (17.9, NR)
Graph showing percentage of living patients at 2 years
Graph showing percentage of living patients at 2 years

Number of subjects at risk
Months BREYANZI Standard therapy
0 92 92
1 92 88
2 88 81
3 84 79
4 81 74
5 78 66
6 74 62
7 68 60
8 63 58
9 43 41
10 34 30
11 30 21
12 16 15
13 13 12
14 10 10
15 7 5
16 5 3
17 1 1
18 0 1
Overall survival (OS) was a secondary endpoint of the TRANSFORM study.4
  • At primary analysis, OS was not statistically significant
  • Data was limited for OS because of the number of patient deaths and was based on the ITT principle
  • Estimates were not adjusted for patient crossover
  • Median follow-up in both arms: 17.5 months.
OS is defined as the time from randomization to death due to any cause.
CI, confidence interval; CR, complete response; DoCR, duration of complete response; EFS, event-free survival; HR, hazard ratio; IRC, independent review commitee; ITT, intent-to-treat; LBCL, large B-cell lymphoma; NR, not reached; mEFS, median event-free survival; mOS, median overall survival; ORR; overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R/R, relapsed or refractory; SCT, stem cell transplant.
* Per the Lugano criteria, as assessed by an IRC.
Based on stratified Cox proportional hazards model.
P-value is compared with 0.012 of the allocated alpha this prespecified interim analysis.
§ P-value is compared with 0.021 of the allocated alpha for the primary analysis.
The tick marks represent censored patients. Patients alive or lost to follow up by data cutoff were censored at the last date known to be alive.
TRANSFORM trial1
2L TRANSFORM trial process
2L TRANSFORM trial process
  • Primary endpoint: EFS2
  • Select secondary endpoints: CR rate, PFS, OS, ORR, DoCR2
Trial design was patient-centric, allowing for crossover to the Breyanzi arm
from the standard therapy arm2
Patients receiving standard therapy treatment were allowed to receive Breyanzi if they failed to achieve CR or PR after 3 cycles of salvage immunochemotherapy, or had disease progression at any time, or if the patient needed to start a new treatment due to efficacy concerns.2
TRANSFORM trial design and patient disposition1
Breyanzi arm (N=92)1
Patients randomized to Breyanzi were to receive lymphodepleting chemotherapy consisting of fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day concurrently for 3 days followed by Breyanzi infusion 2 to 7 days after completion of lymphodepleting chemotherapy. Breyanzi planned dose of 100 × 106 CAR+ T cells.
Bridging chemotherapy was permitted between leukapheresis and the start of lymphodepleting chemotherapy.
  • Of 92 patients randomized to receive Breyanzi, 89 (97%) received Breyanzi
  • Fifty-eight (63%) patients received bridging therapy
  • One (1.1%; manufacturing failure) patient received a nonconforming product
Standard therapy arm (N=92)1
  • Of the 92 patients randomized to receive standard therapy, 91 started treatment and 43 (47%) received high-dose therapy and HSCT
The most common reason for not receiving HSCT was lack of efficacy of the salvage chemotherapy
21% of Breyanzi patients were treated in an outpatient setting
per physicians’ discretion1
Think Breyanzi next for patients who are primary refractory or relapsed
in ≤12 months after 1 prior line of therapy
Select demographics1,2
Characteristics1,2 Characteristics (N=184)
Age, range Median 59; 20-75 years
ECOG PS 0/1 at screening 57% / 42%
Primary refractory 73%
Relapsed 27%
LBCL subtypes
DLBCL NOS 55%
High-grade B-cell lymphoma 23%
Primary mediastinal large B-cell lymphoma 10%
DLBCL transformed from indolent lymphoma 8%
Secondary CNS involvement 2%
* Standard therapy regimens administered, as per the investigator's decision, were R-DHAP, R-ICE, or R-GDP.
Lymphodepleting chemotherapy regimen consisted of fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day.
CAR, chimeric antigen receptor; CNS, central nervous system; CR, complete response; DLBCL, diffuse large B-cell lymphoma, DoCR, duration of complete response; ECOG PS, Eastern Cooperative Oncology Group performance status; EFS, event-free survival; HSCT, hematopoietic stem cell transplant; HDT, high-dose therapy; LBCL, large B-cell lymphoma; LDC, lymphodepleting chemotherapy; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PR, partial response; R-DAHP, Rituximab, Dexamethasone, Cytarabine, and Cisplatin; R-GDP, Rituximab, Gemcitabine, Dexamethasone, and Cisplatin; R-ICE, Rituximab, Ifosfamide, Carboplatin, and Etoposide; R/R, relapsed or refractory; SCT, stem cell transplant.
74% of patients treated with Breyanzi experienced deep and durable complete response5*
Breyanzi
(N=92)
Standard therapy (N=92)*
ORR5 87% (80/92, 95% CI: 78.3, 93.1) 49% (45/92, 95% CI: 38.3, 59.6)
CR5 74% (68/92, 95% CI: 63.7, 82.5)ठ43% (40/92, 95% CI: 33.2, 54.2)
mDoCR5 NR (95% CI: NR, NR) 9.3 months (95% CI: 5.1, NR)
More than twice as many patients in the Breyanzi arm went on to receive treatment1
  • 97% of patients (89/92) received Breyanzi
  • 47% of patients (43/92) received treatment with HDT + HSCT in the standard therapy arm
CI, confidence interval; CR, complete response; HDT, high-dose therapy; HSCT, hematopoietic stem cell transplant; mDoCR, median duration of complete response; NR, not reached; ORR, overall response rate; PR, partial response.
* At 17.5 months median follow-up.
Interim 6.2-month median follow-up: CR of 66% for Breyanzi vs 39% for standard therapy.
Per the Lugano criteria, as assessed by an IRC.
§ P<0.0001; Cochran-Mantel-Haenszel test. P-value is compared with 0.021 of the allocated alpha for the primary analysis.

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