If you wish to report an adverse event or product complaint, please call 1-800-LILLYRX (1-800-545-5979)
Jaypirca ® (pirtobrutinib) tablets
50 mg,100 mg
This information is provided in response to your request. Resources may contain information about doses, uses, formulations and populations different from product labeling. See Prescribing Information above, if applicable.
What are the efficacy and safety results for the Jaypirca™ (pirtobrutinib) in the phase 1/2 BRUIN trial?
In a phase 1/2 BRUIN study, Jaypirca (pirtobrutinib) has shown efficacy in heavily pretreated patients with various B-cell malignancies and the most common TEAEs included fatigue, diarrhea, and neutropenia.
Efficacy Results in Phase 1/2 BRUIN Study
BRUIN is a global, multicenter phase 1/2 trial evaluating pirtobrutinib (LOXO-305) in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin's lymphoma (NHL) who have failed or are intolerant to standard of care (NCT03740529).1,2 BRUIN Phase 1/2 Study Schema provides additional details on the BRUIN study design.
Mantle Cell Lymphoma
As of the data cut-off date on July 29, 2022, 773 patients had been enrolled in the BRUIN trial, of which 166 were patients with mantle cell lymphoma (MCL). Efficacy analysis was performed in the first 90 patients with MCL who had
- measurable disease
- enrolled in either phase 1 or phase 2
- received a prior Bruton's tyrosine kinase (BTK) inhibitor-containing regimen, and
- no central nervous system involvement.3
Efficacy Results Among Patients With MCL in the Phase 1/2 BRUIN Study presents efficacy for patients with MCL in the by prior treatment with a BTK inhibitor as of the data cutoff of July 29, 2022.3
Response, n (%) |
MCL (cBTKi-naïve)a |
MCL (Previous cBTKi)b |
85.7 (57.2-98.2) |
56.7 (45.8-67.1) |
|
CR |
6 (42.9) |
17 (18.9) |
PR |
6 (42.9) |
34 (37.8) |
SD |
0 |
16 (17.8) |
Median DOR, months (95% CI) |
NR |
17.6 (7.3-27.2) |
Median PFS, months (95% CI) |
NR |
7.4 (5.3-13.3) |
Median OS, months (95% CI) |
NR |
23.5 (15.9-NE) |
Abbreviations: cBTKi = covalent Bruton's tyrosine kinase inhibitor; CR = complete response; DOR = duration of response; IRC = independent review committee; MCL = mantle cell lymphoma; NE = not estimable; NR = not reported; OS = overall survival; PFS = progression-free survival; PR = partial response; SD = stable disease.
aOne cBTKi naïve patient was not evaluable.
bPrimary analysis set. Nine cBTKi pre-treated MCL patients were not evaluable.
cORR includes patients with a best response of CR and PR.
dResponse status per Lugano 2014 criteria based on IRC assessment.
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
As of the data cut-off date on July 29, 2022, 773 patients had been enrolled in the BRUIN trial, of which 317 were patients with CLL or SLL. Efficacy analysis was performed in 247 patients with CLL/SLL who had
- enrolled in either phase 1 or phase 2 prior to November 5, 2021
- received a prior BTK inhibitor-containing regimen, and
- received one or more doses of pirtobrutinib.4
Efficacy Results Among Patients With CLL/SLL Who Received Prior BTK Inhibitor Treatment in the Primary Analysis Set of the Phase 1/2 BRUIN Study presents efficacy for patients with CLL/SLL who received prior BTK inhibitor treatment in the efficacy analysis set.4
Response, n (%) |
CLL/SLL |
ORRa, % (95% CI) |
82.2 (76.8-86.7) |
CR |
4 (1.6) |
Nodular PR |
1 (0.4) |
PR |
176 (71.3) |
PR-L |
22 (8.9) |
SD |
26 (10.5) |
Median PFS, months (95% CI)b |
19.6 (16.9-22.1) |
12-month PFS, % |
68.9 |
Abbreviations: BTK = Bruton's tyrosine kinase; CLL = chronic lymphocytic leukemia; CR = complete response; IRC = independent review committee; iwCLL = International Workshop on Chronic Lymphocytic Leukemia; PFS = progression-free survival; PR = partial response; PR-L = partial response with lymphocytosis; SD = stable disease; SLL = small lymphocytic lymphoma.
aIncludes patients with a best response of CR, PR, and PR-L. Response status per iwCLL 2018 according to IRC assessment.
bMedian follow-up of 19.4 months.
Other Non-Hodgkin's Lymphomas
In the BRUIN study, patients with other B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL), Waldenström's macroglobulinemia (WM), follicular lymphoma (FL), marginal zone lymphoma (MZL), Richter's transformation (RT), B-cell prolymphocytic leukemia (B-PLL), Hairy Cell Leukemia, primary central nervous system lymphoma (PCNSL), and other transformations, were permitted to enroll.5 Additional efficacy details on these subgroups are included below.
Richter's Transformation
As of the data cut-off date on July 29, 2022, 773 patients had been enrolled in the BRUIN trial, of which 82 were patients with RT. Efficacy analysis was performed in 75 patients with RT who had ≥1 post-baseline response assessment or discontinued treatment prior to first post-baseline response assessment. Of these 75 patients, 68 patients had received prior RT-directed treatment.6
Efficacy Results Among Patients With RT in the Phase 1/2 BRUIN Study presents efficacy for patients with RT as of the data cutoff of July 29, 2022.6
Response, n (%) |
All RT Patients |
Prior RT Treatment |
ORRa, % (95% CI) |
52.0 (40.2-63.7) |
50.0 (37.6-62.4) |
CR |
10 (13.3) |
9 (13.2) |
PR |
29 (38.7) |
25 (36.8) |
SD |
10 (13.3) |
10 (14.7) |
Median DOR, months (95% CI) |
5.6 (2.5-NE) |
5.4 (1.9-NE) |
Median PFS, months (95% CI) |
3.7 (2.9-5.1) |
3.6 (2.7-4.9) |
Median OS, months (95% CI) |
13.1 (7.8-NE) |
12.8 (7.1-NE) |
Abbreviations: CR = complete response; DOR = duration of response; NE = not estimable; OS = overall survival; PFS = progression-free survival; PR = partial response; RT = Richter's transformation; SD = stable disease.
aResponse as assessed by investigator based on Lugano criteria.
Waldenström's Macroglobulinemia
As of the data cut-off date on July 29, 2022, 773 patients had been enrolled in the BRUIN trial, of which 80 were patients with WM. Of these 80 patients, 63 patients had received prior BTK inhibitor treatment.7
Efficacy Results Among Patients With WM in the Phase 1/2 BRUIN Study presents efficacy for patients with RT.7
WM (cBTKi-naïve) |
WM (Previous cBTKi) |
|
Major response ratec, % (95% CI) |
88.2 (63.6-98.5) |
66.7 (53.7-78.0) |
CR + VGPR, % (95% CI) |
29.4 (10.3-56.0) |
23.8 (14.0-36.2) |
Best response, n (%) |
||
VGPRd |
5 (29.4) |
15 (23.8) |
PR |
10 (58.8) |
27 (42.9) |
MR |
0 |
9 (14.3) |
SD |
2 (11.8) |
9 (14.3) |
Median PFS, months (95% CI) |
NR |
19.4 (15.1-22.1) |
Median OS, months (95% CI) |
NR |
NE |
Abbreviations: cBTKi = covalent Bruton's tyrosine kinase inhibitor; CR = complete response; MR = minor response; NE = not estimable; NR= not reported; OS = overall survival; PFS = progression-free survival; PR = partial response; SD = stable disease; VGPR = very good partial response; WM = Waldenström's macroglobulinemia.
aResponse as assessed by investigator based on Modified IWWM6 (Owen’s) criteria.
bTotal % may be different than the sum of the individual components due to rounding.
cMajor response includes subjects with a best response of CR, VGPR, or PR.
dUnder modified IWWM6 criteria, a PR is upgraded to VGPR if corresponding IgM is in normal range or has at least 90% reduction from baseline.
Follicular Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma
Efficacy Results Among Patients With Other Non-Hodgkin's Lymphomas in the Phase 1/2 BRUIN Study shows efficacy was also demonstrated in other NHLs as of September 27, 2020.
Responseb |
FL |
MZL |
DLBCL |
ORRc, % (95% CI) |
50 (16-84) |
22 (3-60) |
24 (9-45) |
CR, n (%) |
2 (25) |
0 |
4 (16) |
PR, n (%) |
2 (25) |
2 (22) |
2 (8) |
SD, n (%) |
1 (13) |
7 (78) |
2 (8) |
Abbreviations: CR = complete response; DLBCL = diffuse large B-cell lymphoma; FL = follicular lymphoma; MZL = marginal zone lymphoma; ORR = overall response rate; PR = partial response; SD = stable disease.
aEfficacy evaluable patients are those who had at least one postbaseline response assessment or had discontinued treatment prior to first postbaseline response assessment.
bTotal percentage may be different than the sum of the individual components due to rounding.
cResponses were defined according to disease-specific guidelines. As of data cutoff, no responses were observed in the efficacy evaluable patients with other tumor types not shown in the table. ORR includes patients with a best response of CR and PR. Response status per Lugano criteria.
Safety Results in Phase 1/2 BRUIN Study
The median time on treatment for the overall safety population was 9.6 months. Treatment-related adverse events led to
- treatment discontinuations in 2.6% (n=20) of all patients, and
- dose reductions in 4.5% (n=35) of all patients.6
Adverse events that occurred in ≥15% of patients in the overall BRUIN study are summarized in Adverse Events Occurring in ≥15% of the Overall Study Population of the Phase 1/2 BRUIN Study . Adverse events of special interest in the overall BRUIN study are summarized in Adverse Events of Special Interest Among Patients in the Overall Study Population of the the Phase 1/2 BRUIN Study.
Adverse Event, % of patients |
All Doses and Patients |
|||
TEAEs |
TRAEs |
|||
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
|
Fatigue |
28.7 |
2.1 |
9.3 |
0.8 |
Diarrhea |
24.2 |
0.9 |
9.3 |
0.4 |
Neutropeniaa |
24.2 |
20.4 |
14.7 |
11.5 |
Contusion |
19.4 |
0 |
12.8 |
0 |
Cough |
17.5 |
0.1 |
2.3 |
0 |
Covid-19 |
16.7 |
2.7 |
1.3 |
0 |
Nausea |
16.2 |
0.1 |
4.7 |
0.1 |
Dyspnea |
15.5 |
1.0 |
3.0 |
0.1 |
Anemia |
15.4 |
8.8 |
5.2 |
2.1 |
Abbreviations: TEAE = treatment-emergent adverse event; TRAE = treatment-related adverse event.
aAggregate of neutropenia and neutrophil count decreased.
Adverse Event of Special Interesta, % of patients |
All Doses and Patients |
|||
TEAEs |
TRAEs |
|||
Any Grade |
Grade ≥3 |
Any Grade |
Grade ≥3 |
|
Bruisingb |
23.7 |
0 |
15.1 |
0 |
Rashc |
12.7 |
0.5 |
6.0 |
0.4 |
Arthralgia |
14.4 |
0.6 |
3.5 |
0 |
Hemorrhage/hematomad |
11.4 |
1.8 |
4.0 |
0.6 |
Hypertension |
9.2 |
2.3 |
3.4 |
0.6 |
Atrial fibrillation/fluttere |
2.8f |
1.2 |
0.8 |
0.1 |
Abbreviations: BTK = Bruton's tyrosine kinase; TEAE = treatment-emergent adverse event; TRAE = treatment-related adverse event.
aAdverse events of special interest are those that were previously associated with covalent BTK inhibitors.
bAggregate of contusion, petechiae, ecchymosis, and increased tendency to bruise.
cAggregate of all preferred terms including rash.
dAggregate of all preferred terms including hematoma or hemorrhage.
eAggregate of atrial fibrillation and atrial flutter.
fOf the 22 total atrial fibrillation/atrial flutter TEAEs in the overall safety population, 7 occurred in patients with a prior medical history of atrial fibrillation.
Patient Characteristics in Phase 1/2 BRUIN Study
Baseline patient characteristics and treatment history among patients with MCL, CLL/SLL, RT, and WM in the BRUIN study are summarized in Baseline Characteristics Among Patients with MCL, CLL/SLL, RT, and WM in the Phase 1/2 BRUIN Study and Treatment History Among Patients with MCL, CLL/SLL, RT, and WM in the Phase 1/2 BRUIN Study, respectively.
Characteristic |
MCL (prior BTKi)3 |
CLL/SLL9 |
RT6 |
WM (prior BTKi)7 |
Median age, years (range) |
70 (46-87) |
69 (36-88) |
67 (26-95) |
69 (42-84) |
Male, n (%) |
72 (80) |
168 (68) |
55 (67) |
42 (67) |
ECOG PS, n (%) |
||||
0 |
61 (68) |
133 (54) |
32 (39) |
34 (54) |
1 |
28 (31) |
97 (39) |
38 (46) |
28 (44) |
2 |
1 (1) |
17 (7) |
12 (15) |
1 (2) |
Median lines of prior systemic therapy, (range) |
3 (1-8) |
3 (1-11) |
2 (0-13) |
3 (1-11) |
Progressive disease |
74 (82) |
190 (77) |
NR |
41 (65) |
Toxicity/other |
16 (18) |
57 (23) |
NR |
21 (33) |
Abbreviations: BTKi = Bruton's tyrosine kindase inhibitor; CLL = chronic lymphocytic leukemia; ECOG = Eastern Cooperative Oncology Group; MCL = mantle cell lymphoma; PS = performance status; RT = Richter's transformation; SLL = small lymphocytic lymphoma; WM = Waldenström's macroglobulinemia.
aData cutoff of July 29, 2022.
bIn the event more than one reason was noted for discontinuation, disease progression took priority.
cOne patient with WM had unknown reason for prior BTK inhibitor discontinuation.
Prior Therapy, n (%) |
MCL (prior BTKi)3 |
CLL/SLL9 |
RT6 |
WM (prior BTKi)7 |
BTK inhibitor |
90 (100) |
247 (100) |
28 (34) |
63 (100) |
Anti-CD20 antibody |
86 (96) |
217 (88) |
64 (78) |
58 (92) |
Chemotherapy |
79 (88) |
195 (79) |
62 (76) |
52 (83) |
BCL2 inhibitor |
14 (16) |
100 (41) |
31 (38) |
4 (6) |
PI3K inhibitor |
3 (3) |
45 (18) |
8 (10) |
3 (5) |
CAR-T |
4 (4) |
14 (6) |
9 (11) |
NR |
Stem cell transplant |
19 (21) |
6 (2) |
5 (6) |
4 (6) |
Immunomodulator |
19 (21) |
NR |
3 (4) |
6 (10) |
Abbreviations: BCL2 = B-cell lymphoma-2; BTK = Bruton's tyrosine kinase; CAR-T = chimeric antigen receptor T cells; CLL = chronic lymphocytic leukemia; MCL = mantle cell lymphoma; NR = not reported; PI3K = phosphatidylinositol-3-kinase; RT = Richter’s transformation; SLL = small lymphocytic lymphoma; WM = Waldenström's macroglobulinemia.
aData cutoff of July 29, 2022.
BRUIN Phase 1/2 Clinical Study
The primary endpoints of the phase 1 portion of the BRUIN study are maximum tolerated dose and recommended phase 2 dose. The primary endpoint of the phase 2 portion of the study is overall response rate by independent review committee. Key secondary endpoints of the phase 2 portion of the study are
- duration of response
- overall survival
- progression free survival
- safety and tolerability, and
- pharmacokinetics.1,2
BRUIN Phase 1/2 Study Schema describes the design of the BRUIN study.