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Jaypirca ® (pirtobrutinib) tablets
50 mg,100 mg
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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 January 27, 2025, 778 patients had been enrolled in the BRUIN trial, of which 166 were patients with MCL. Efficacy analysis was performed in 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.3-5
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 January 27, 2025.5
Responsea |
Patients with MCL (Previous cBTKi)b |
49.3 (41.1-57.6) |
|
CR |
24 (15.8) |
PR |
51 (33.6) |
Median DOR, months (95% CI) |
21.6 (9.2-27.2) |
Median PFS, months (95% CI) |
5.6 (5.3-9.2) |
Median OS, months (95% CI) |
23.9 (17.3-51.5) |
Median time to first response, months (range) |
1.8 (0.8-13.8) |
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; OS = overall survival; PFS = progression-free survival; PR = partial response; SD = stable disease.
aPresented as n (%) unless noted.
bThirteen cBTKi pre-treated MCL patients were not evaluable and are included in denominator.
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 a data cut-off date of January 27, 2025, 778 patients had been enrolled in the BRUIN trial, of which 317 were patients with CLL/SLL. Efficacy analyses were performed in 282 patients with CLL/SLL enrolled in either phase 1 or phase 2, who had received ≥1 dose of pirtobrutinib monotherapy at any dose level and who had received a prior BTK-inhibitor-containing regimen. Of these patients, 154 had no prior B-cell lymphoma-2 inhibitor (BCL2i) treatment and were considered BCL2i naive, and 128 patients had prior exposure to a BCL2i. 6
The overall response rate was 81.6% while the median PFS was 18.7 months (95% CI, 16.6-21.8).6 The median duration of response was 18.4 months (95% CI, 14.8-20.3). Efficacy Results of Pirtobrutinib in CLL/SLL Patients Previously Treated With a BTK Inhibitor in the Phase 1/2 BRUIN Study presents additional efficacy outcomes.
Endpoint |
CLL/SLL Efficacy Population |
81.6 (76.5-85.9) |
|
Best response |
|
CR, n (%) |
11 (3.9) |
CRi, n (%) |
1 (0.4) |
Nodular PR, n (%) |
3 (1.1) |
PR, n (%) |
189 (67.0) |
PR-L, n (%) |
26 (9.2) |
Median PFS, months (95% CI)c |
18.7 (16.6-21.8) |
Median OS, months (95% CI)d |
NE (47.8-NE) |
23.2 (20.3-8-29.4) |
|
Abbreviations: BTK = Bruton's tyrosine kinase; cBTKi = covalent Bruton's tyrosine kinase inhibitor; CLL = chronic lymphocytic leukemia; CR = complete response; CRi = CR with incomplete bone marrow recovery; IRC = independent review committee; iwCLL = International Workshop on Chronic Lymphocytic Leukemia; NE = not evaluable; ORR = overall response rate; OS = overall survival; PFS = progression free survival; PR = partial response; PR-L = partial response with lymphocytosis; SLL= small lymphocytic lymphoma; TTNT = time to next treatment.
aORR including PR-L is the number of patients with best response of PR-L or better divided by the total number of patients; 14 patients with a best response of NE are included in the denominator.
bResponse status per iwCLL 2018 based on IRC assessment.
cMedian follow-up of 44.2 months.
dMedian follow-up for 46.5 months.
eMedian follow-up of 49.9 months.
fIncludes death as an event.
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.7 Additional efficacy details on these subgroups are included below.
Richter's Transformation
As of the data cutoff of May 05, 2023, there were 82 patients with Richter transformation (RT) enrolled in the BRUIN trial and 74 of these patients had received prior RT-directed treatment. Patients were eligible for participation in the RT subgroup if they
- were ≥18 years of age
- had Eastern Cooperative Oncology Group Performance Status score of 0-2
- had histologically confirmed, active RT, and
- were either previously treated for RT or were frontline RT patients.8
There was no limit on the number of prior lines of treatment and prior treatment with covalent Bruton's tyrosine kinase (BTK) inhibitors were permitted.8
Efficacy Results Among Patients With Richter Transformation in the Phase 1/2 BRUIN Study summarizes the efficacy results among patients with RT in the BRUIN study, as assessed by the investigator based on Lugano criteria. The median time on treatment for all RT patients (N=82) was 3.6 months (range, 0.2-26.7).8
Efficacy Endpointa |
All RT Patients |
ORR, % (95% CI) |
|
Best response, n (%) |
|
CR |
11 (13.4) |
PR |
30 (36.6) |
SD |
11 (13.4) |
PD |
20 (24.4) |
Not evaluable |
10 (12.2) |
Median PFS, months (95% CI) |
|
Median OS, months (95% CI) |
|
Median DOR, months (95% CI) |
|
Abbreviations: alloSCT = allogenic stem cell transplantation; CAR-T = chimeric antigen receptor T-cell; CR = complete response; DOR = duration of response; NE = not estimable; ORR = overall response rate; OS = overall survival; PD = progressive disease; PFS = progression-free survival; PR = partial response; RT = Richter transformation; SD = stable disease.
aResponse was assessed based on Lugano criteria.
bMedian time-to-response was 1.9 months (range, 0.9-9.2) among the RT patient cohort.
cOverall response rate was the number of patients with best response of CR and PR divided by total number of patients; 10 patients with a not evaluable best response were included in the denominator.
dMedian follow-up was 13.8 months among 82 response-evaluable patients.
eEight responding patients were censored at the time of last adequate disease assessment prior to pursuing curative intent stem cell therapy.
fMedian follow-up was 18.3 months among 82 response-evaluable patients.
gNineteen patients including 14 responders on pirtobrutinib treatment pursued subsequent alloSCT or CAR-T therapy.
hMedian follow-up was 9.7 months among 41 response-evaluable patients.
Waldenström's Macroglobulinemia
Efficacy Results Among Patients With WM in the Phase 1/2 BRUIN Study summarizes the efficacy results among patients with WM in the BRUIN study, as assessed by the investigator based on the modified 6th International Workshops on WM (IWWM-6; Owen’s) criteria. The median study follow-up was 35.0 months (range: 2.7-62.9). The median overall survival (OS) was not reached in the entire WM cohort, with a 36-month OS rate of 67.5%.10
Overall, 96% of patients (72/75) showed a reduction in immunoglobulin M levels, with a median decrease of 75.5% (interquartile range: 54.6–88.5) from baseline.10
Efficacy Parametersa |
|||
Prior cBTKi Treated |
cBTKi Naïve |
All WM Patients |
|
Major response rate, % (95% CI)b |
68.3 (55.3-79.4) |
88.2 (63.6-98.5) |
72.5 (61.4-81.9) |
CR + VGPR rate, % (95% CI)c |
25.4 (15.3-37.9) |
35.3 (14.2-61.7) |
27.5 (18.1-38.6) |
ORRd, n (%) |
51 (81.0) |
15 (88.2) |
66 (82.5) |
Best response, n (%) |
|||
CR |
1 (1.6) |
0 |
1 (1.3) |
VGPR |
15 (23.8) |
6 (35.3 |
21 (26.3) |
PR |
27 (42.9) |
9 (52.9) |
36 (45.0) |
MR |
8 (12.7) |
0 |
8 (10.0) |
SD |
9 (14.3) |
2 (11.8) |
11 (13.8) |
Median DOR, months (95% CI) |
20.3 (15.8-NE) |
NR (42.3-NE) |
42.3 (17.9-NE) |
Median PFSe, months (95% CI) |
19.6 (15.1-38.5) |
NR (13.6-NE) |
35.9 (19.3-NE) |
36-month PFS rate, % |
39.0 |
76.5 |
48.4 |
Median OS, months (95% CI) |
NR (38.5-NE) |
NR (19.6-NE) |
NR (NE-NE) |
36-month OS rate, % |
64.5 |
76.5 |
67.5 |
Abbreviations: cBTKi = covalent Bruton's tyrosine kinase inhibitor; CR = complete response; DOR = duration of response; IgM = immunoglobulin M; IWWM6 = 6th International Workshops on WM; MR = minor response; NE = not estimable; ORR = overall response rate; PFS = progression-free survival; PR = partial response; OS = overall survival; SD = stable disease; VGPR = very good partial response; WM = Waldenström macroglobulinemia.
aResponse was assessed by the investigator based on Modified IWWM6 (Owen’s) criteria. Under modified IWWM6 criteria, a PR is upgraded to VGPR if corresponding IgM is in normal range or has at least 90% reduction from baseline.
bMajor response includes patients with a best response of CR, VGPR, or PR.
cThe CR/VGPR rate in patients who previously discontinued cBTKi due to progressive disease was 22.0% (9/41).
dIncludes patients with a best response of CR, VGPR, PR or MR.
eInvestigator assessed.
Follicular Lymphoma
As of the data cutoff of January 27, 2025, there were 48 patients with FL enrolled in the BRUIN trial. Patients with histologically confirmed active follicular lymphoma who had received at least one prior regimen were eligible for inclusion in the FL subgroup.11
Efficacy Results Among Patients With Follicular Lymphoma in the Phase 1/2 BRUIN Study summarizes the efficacy results among patients with FL in the BRUIN study.
At 24 months, the estimated
- progression-free survival rate was 25.6%; 95% CI, 13.9-39.1
- overall survival rate was 75.1%; 95% CI, 59.5-85.4, and
- duration of response rate was 33.3%; 95% CI, 15.9-51.9.11
Among 4 patients previously treated with covalent Bruton's tyrosine kinase inhibitor, 3 achieved partial response and 1 had stable disease.11
Efficacy Endpoint |
All FL Patients |
52.1 (37.2-66.7)c |
|
Best response, n (%) |
|
CR |
8 (16.7) |
PR |
17 (35.4) |
Median PFS, months (95% CI) |
5.8 (3.8-8.1)d |
Median OS, months (95% CI) |
NEe |
Median DOR, months (95% CI) |
10.2 (3.7-25.7)f |
Abbreviations: CR = complete response; DOR = duration of response; FL = follicular lymphoma; NE = not estimable; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; PR = partial response.
aInvestigator-assessed ORR according to Lugano 2014 criteria.
bORR is defined as the number of patients with best response of CR or PR divided by the total number of patients; 1 patient with a best response of not evaluable is included in the denominator.
cMedian time-to-response was 1.9 months (range, 1.6-7.5) among responding patients.
dMedian follow-up was 44.2 months among 48 response-evaluable patients.
eMedian follow-up was 35.2 months among 48 response-evaluable patients.
fMedian follow-up was 40.5 months (interquartile range, 31.6-43.5) among 25 response-evaluable patients.
Marginal Zone Lymphoma
As of the data cutoff of May 05, 2023, there were 36 patients with marginal zone lymphoma (MZL) enrolled in the BRUIN trial. Patients were eligible for participation in the MZL subgroup if they had active MZL in need of treatment and had previously been treated for the disease.12
Efficacy Results Among Patients With Marginal Zone Lymphoma in the Phase 1/2 BRUIN Study summarizes the efficacy results among patients with MZL in the BRUIN study, as assessed according to Lugano criteria. At 18 months, the
- progression-free survival rate was 46.6%
- overall survival rate was 81.8%, and
- duration of response rate was 35.8%.12
Efficacy Endpointa |
All MZL Patients |
Prior cBTKi Treated |
cBTKi Naive |
ORR |
50.0 (32.9-67.1)b |
46.2 (26.6-66.6) |
60.0 (26.2-87.8) |
Best response, n (%) |
|||
CR |
1 (2.8) |
0 |
1 (10.0) |
PR |
17 (47.2) |
12 (46.2) |
5 (50.0) |
Median PFS, months |
16.5 (7.4-22.1)c |
9.2 (5.8-NE) |
NE (1.9-NE) |
Median OS, months |
NE (27.6-NE)d |
NE |
NE (11.7-NE) |
Median DOR, months |
12.7 (5.6-NE)e |
7.4 (3.8-12.7) |
NE (12.0-NE) |
Abbreviations: cBTKi = covalent Bruton's tyrosine kinase inhibitor; CR = complete response; DOR = duration of response; MZL = marginal zone lymphoma; NE = not estimable; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; PR = partial response.
aEfficacy assessment based on Lugano criteria.
bMedian time-to-response was 1.9 months (range, 1.6-19.3) among 29 response-evaluable patients.
cMedian follow-up was 15.8 months among 36 response-evaluable patients.
dMedian follow-up was 21.5 months among 36 response-evaluable patients.
eMedian follow-up was 17.6 months among 18 response-evaluable patients.
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 |
DLBCL |
ORRc, % (95% CI) |
24 (9-45) |
CR, n (%) |
4 (16) |
PR, n (%) |
2 (8) |
SD, n (%) |
2 (8) |
Abbreviations: CR = complete response; DLBCL = diffuse large B-cell 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
As of July 29, 2022, 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.14
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, WM, FL, and MZL in the BRUIN study are summarized in Baseline Characteristics Among Patients with MCL, CLL/SLL, RT, WM, FL, and MZL in the Phase 1/2 BRUIN Study and Treatment History Among Patients with MCL, CLL/SLL, RT, WM, FL, and MZL in the Phase 1/2 BRUIN Study, respectively.
Characteristic |
||||||
Median age, years (range) |
70 (46-88) |
69 (36-88) |
67 (26-95) |
69 (42-84) |
64.5 (37-85) |
68 (22-83) |
Male, n (%) |
120 (79) |
192 (68) |
55 (67) |
42 (67) |
29 (60) |
16 (44) |
ECOG PS, n (%) |
||||||
0 |
93 (61) |
144 (51) |
32 (39) |
34 (54) |
26 (54) |
18 (50) |
1 |
56 (37) |
118 (42) |
38 (46) |
28 (44) |
22 (46) |
17 (47) |
2 |
3 (2) |
20 (7) |
12 (15) |
1 (2) |
0 |
1 (3) |
Median lines of prior systemic therapy, (range) |
3 (1-9) |
4 (1-11) |
2 (0-13) |
3 (1-11) |
3 (1-12) |
3 (2-10) |
Progressive disease |
128 (84) |
217 (77) |
NR |
41 (65) |
3 |
20 (77) |
Toxicity/other |
21 (14) |
64 (23) |
NR |
14 (22.2)/7 (11.1) |
1 |
6 (23) |
Abbreviations: BTKi = Bruton's tyrosine kinase inhibitor; CLL = chronic lymphocytic leukemia; ECOG = Eastern Cooperative Oncology Group; FL = follicular lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma; NR = not reported; PS = performance status; RT = Richter's transformation; SLL = small lymphocytic lymphoma; WM = Waldenström's macroglobulinemia.
aData cutoff January 27, 2025.
bData cutoff of May 5, 2023.
cIn the event more than one reason was noted for discontinuation, disease progression took priority.
dOne patient with WM and 3 patients with MCL had unknown reason for prior BTK inhibitor discontinuation.
Prior Therapy, n (%) |
||||||
BTK inhibitor |
152 (100) |
282 (100) |
61 (74) |
63 (100) |
4 (8) |
26 (72) |
Anti-CD20 antibody |
147 (97) |
251 (89) |
80 (98) |
58 (92) |
48 (100) |
36 (100) |
Chemotherapy |
137 (90) |
228 (81) |
73 (89) |
52 (83) |
43 (90)c |
31 (86)c |
BCL2 inhibitor |
24 (16) |
128 (45) |
56 (68) |
4 (6) |
3 (6) |
1 (3) |
PI3K inhibitor |
6 (4) |
71 (25) |
12 (15) |
3 (5) |
17 (35) |
6 (17) |
CAR-T |
13 (9) |
17 (6) |
11 (13) |
NR |
4 (8) |
NR |
Stem cell transplant |
33 (22) |
7 (3)d |
10 (12) |
4 (6) |
6 (13)e |
1 (3)e |
Immunomodulator |
26 (17) |
NR |
7 (9)f |
6 (10) |
14 (29)g |
8 (22)g |
Abbreviations: BCL2 = B-cell lymphoma-2; BTK = Bruton's tyrosine kinase; CAR-T = chimeric antigen receptor T cells; CLL = chronic lymphocytic leukemia; FL = follicular lymphoma; MCL = mantle cell lymphoma; MZL = marginal zone lymphoma; NR = not reported; PI3K = phosphatidylinositol-3-kinase; RT = Richter’s transformation; SLL = small lymphocytic lymphoma; WM = Waldenström's macroglobulinemia.
aData cutoff January 27, 2025.
bData cutoff of May 5, 2023.
cChemotherapy plus anti-CD20 antibody.
dAllogenic stem cell transplant.
eAutologous stem cell transplant.
fImmunomodulators include lenalidomide and pomalidomide.
gLenalidomide.
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.
Figure 1 description: The phase 1 dose escalation study enrolled patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, or B-cell non-Hodgkin's lymphoma who had received at least 2 prior standard of care regimens given in combination or sequentially or 1 prior Bruton's tyrosine kinase inhibitor-containing regimen when a Bruton's tyrosine kinase inhibitor was approved as first-line therapy. Once a maximum tolerated dose and/or recommended phase 2 dose had been determined, patients were enrolled to 1 of 7 phase 2 dose expansion cohorts depending on tumor histology and prior treatment history or phase 1b. These 7 cohorts were Cohort 1: patients with non-blastoid mantle cell lymphoma who had received prior Bruton's tyrosine kinase inhibitor; Cohort 2: patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who had received at least 2 prior lines of therapy including Bruton's tyrosine kinase inhibitor; Cohort 3: treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma; Cohort 4: patients with chronic lymphocytic leukemia or small lymphocytic lymphoma who had received prior therapy but not Bruton's tyrosine kinase inhibitor; Cohort 5: patients with Waldenström macroglobulinemia who had received prior therapy including Bruton's tyrosine kinase inhibitor; Cohort 6: patients with marginal zone lymphoma who had received prior therapy including Bruton's tyrosine kinase inhibitor; and Cohort 7: patients who did not fit into one of the other 6 groups.
Abbreviations: BTK = Bruton's tyrosine kinase; CLL = chronic lymphocytic leukemia; MCL = mantle cell lymphoma; MTD = maximum tolerated dose; MZL = marginal zone lymphoma; NHL = non-Hodgkin's lymphoma; RP2D = recommended phase 2 dose; SLL = small lymphocytic lymphoma; SOC = standard of care; WM = Waldenström macroglobulinemia.
Note: This schema focuses on the monotherapy portion of the BRUIN study. Following the completion of phase 1, a phase 1b portion of the study was opened to assess the use of pirtobrutinib in combination with venetoclax ± rituximab.
The estimated primary completion date for the BRUIN study is September 2027, with an estimated study completion date of September 2027.1
Enclosed Prescribing Information
References
The published references below are available by contacting 1-800-LillyRx (1-800-545-5979).
1A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHL. ClinicalTrials.gov identifier: NCT03740529. Updated September 25, 2025. Accessed November 19, 2025. https://www.clinicaltrials.gov/ct2/show/NCT03740529
2Mato AR, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study. Lancet. 2021;397(10277):892-901. https://doi.org/10.1016/S0140-6736(21)00224-5
3Shah NN, Jurczak W, Zinzani PL, et al. Pirtobrutinib in covalent BTK-inhibitor (cBTKi) pre-treated mantle cell lymphoma (MCL): Updated results and subgroup analysis from the phase 1/2 BRUIN study with 2 years of survival follow-up. Poster presented at: 59th Annual Meeting of the American Society of Clinical Oncology (ASCO); June 2-8, 2023; Chicago, Illinois. Accessed June 2, 2023.
4Cohen JB, Shah NN, Jurczak W, et al. Pirtobrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients with prior cBTKi: Updated safety and efficacy including high-risk subgroup analyses from the phase 1/2 BRUIN study. Oral presentation presented at: 65th Annual Meeting of the American Society of Hematology (ASH); December 9-12, 2023; San Diego, California. Accessed December 11, 2023.
5Wang ML, Cohen JB, Shah NN, et al. Pirtobrutinib in relapsed/refractory (R/R) mantle cell lymphoma (MCL): Final update from the phase 1/2 BRUIN study. Oral presentation presented at: 67th Annual Meeting of the American Society of Hematology (ASH); December 6-9, 2025; Orlando, Florida. Accessed December 7, 2025.
6Wierda WG, Brown JR, Ghia P, et al. Pirtobrutinib in post-BTKi CLL/SLL: Final update from the phase 1/2 BRUIN study with more than 5-years follow-up. Poster presented at: 67th Annual Meeting of the American Society of Hematology (ASH); December 6-9, 2025; Orlando, Florida. Accessed December 8, 2025.
7Wang ML, Shah NN, Jurczak W, et al. Efficacy of pirtobrutinib in covalent BTK-inhibitor pre-treated relapsed/refractory mantle cell lymphoma: additional patients and extended follow-up from the phase 1/2 BRUIN study. Poster presented at: 64th Annual Meeting of the American Society of Hematology (ASH); December 10-13, 2022; New Orleans, Louisiana. Accessed December 10, 2022.
8Wierda WG, Shah NN, Cheah CY, et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study [published online ahead of print, 2024 Jul 8]. Lancet Haematology 2024; https://doi.org/10.1016/S2352-3026(24)00172-8.
9Wierda WG, Shah NS, Cheah CY, et al. Pirtobrutinib in Richter transformation: Updated efficacy and safety results with 18-month median survival follow-up from the phase 1/2 BRUIN study. Poster presented at: 65th Annual Meeting of the American Society of Hematology (ASH); December 9-12, 2023; San Diego, California. Accessed December 9, 2023.
10Cheah CN, Patel MR, Eyre TA, et al. Pirtobrutinib in relapsed/refractory (R/R) Waldenström Macroglobulinemia (WM): Up to 5 years of follow-up from the phase 1/2 BRUIN study. Oral presentation presented at: 67th Annual Meeting of the American Society of Hematology (ASH); December 6-9, 2025; Orlando, Florida. Accessed December 6, 2025.
11Shah NN, Zinzani PL, Wang M, et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTKi in R/R follicular lymphoma: phase 1/2 BRUIN study. Blood Adv. Published online August 22, 2025. https://doi.org/10.1182/bloodadvances.2024014975
12Patel K, Vose JM, Nasta SD, et al. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in relapsed /refractory marginal zone lymphoma: Results from phase 1/2 BRUIN study. Poster presented at: 65th Annual Meeting of the American Society of Hematology (ASH); December 9-12, 2023; San Diego, California. Accessed December 9, 2023.
13Wang ML, Shah NN, Alencar AJ, et al. LOXO-305, a next generation, highly selective, non-covalent BTK inhibitor in previously treated mantle cell lymphoma, Waldenström's macroglobulinemia, and other non-Hodgkin lymphomas: results from the phase 1/2 BRUIN study. Poster presented at: 62nd Annual Meeting of the American Society of Hematology (ASH Virtual); December 5-8, 2020. Accessed April 18, 2022. https://www.loxooncology.com/docs/presentations/Wang-MCL-ASH2020-FINAL.pdf
14Wierda WG, Lewis D, Ghia P, et al. Efficacy of pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in Richter transformation: results from the phase 1/2 BRUIN study. Oral presentation presented at: 64th Annual Meeting of the American Society of Hematology (ASH); December 10-13, 2022; New Orleans, Louisiana. Accessed December 10, 2022.
Date of Last Review: December 06, 2025