Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05254743 | A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) | PHASE3 | RECRUITING | 662 | — | — | Jul 22, 2022 | Jan 1, 2028 | Apr 20, 2026 | 144 | United States, Argentina +21 |
| NCT05023980 | A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) | PHASE3 | ACTIVE NOT_RECRUITING | 309 | — | — | Sep 23, 2021 | Oct 1, 2027 | Jan 22, 2026 | 108 | United States, Australia +18 |
| NCT04965493 | A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) | PHASE3 | ACTIVE NOT_RECRUITING | 600 | — | — | Sep 20, 2021 | Oct 1, 2027 | Jan 29, 2026 | 176 | United States, Australia +21 |
| NCT04666038 | Study of LOXO-305 (Pirtobrutinib) Versus Investigator's Choice (Idelalisib Plus Rituximab or Bendamustine Plus Rituximab) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) | PHASE3 | ACTIVE NOT_RECRUITING | 238 | — | — | Mar 9, 2021 | May 1, 2027 | Apr 24, 2026 | 232 | United States, Australia +22 |
| NCT06967610 | Phase II Study of Combined Pirtobrutinib, Venetoclax and Obinutuzumab (PVO) Time-limited Treatment for Patients With Recurrent Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). | PHASE2 | RECRUITING | 40 | — | — | Jul 15, 2025 | Jun 1, 2033 | Nov 6, 2025 | 1 | United States |
| NCT06812715 | Clonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib | PHASE2 | RECRUITING | 40 | — | — | May 5, 2025 | May 1, 2031 | Aug 6, 2025 | 3 | Australia |
| NCT06588478 | A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma | PHASE2 | RECRUITING | 249 | — | — | Jan 3, 2025 | Dec 1, 2028 | May 19, 2026 | 131 | United States, Australia +16 |
| NCT06333262 | Fixed Duration Pirtobrutinib and Obinutuzumab in Chronic Lymphocytic Leukemia | PHASE2 | RECRUITING | 60 | — | — | Apr 22, 2024 | Jul 1, 2032 | Jan 21, 2026 | 4 | United States |
| NCT03740529 | A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL | PHASE1 | COMPLETED | 803 | — | — | Mar 15, 2019 | Dec 23, 2025 | Jan 27, 2026 | 56 | United States, Australia +8 |
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria
Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 Response Criteria
Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018
PFS is defined as the time from the date of randomization to the date of first documentation of progressive disease (PD) or death from any cause, as evaluated by an IRC according to International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5
Overall response rate is defined as the proportion of participants who achieve the best overall response at or before the initiation of subsequent anticancer therapy of CR, CRi, nPR, or PR. ORR will be assessed using International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 response criteria.
Defined by the 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines
Phase I
Phase I
Phase II
For Phase 1b
For Phase 1b
| Arm | Type | Description |
|---|---|---|
| Pirtobrutinib Part 1 | EXPERIMENTAL | Participants will receive pirtobrutinib orally. |
| Ibrutinib | ACTIVE_COMPARATOR | Participants will receive ibrutinib orally. |
| Pirtobrutinib Part 2 | EXPERIMENTAL | Participants will receive pirtobrutinib orally. |
| Arm A (Pirtobrutinib) | EXPERIMENTAL | Pirtobrutinib administered orally |
| Arm B (BR) | ACTIVE_COMPARATOR | Bendamustine plus rituximab administered intravenously (IV) |
| Arm A (PVR) | EXPERIMENTAL | Fixed duration pirtobrutinib in combination with venetoclax and rituximab |
| Arm B (VR) | ACTIVE_COMPARATOR | Venetoclax with rituximab |
| Arm A - Pirtobrutinib | EXPERIMENTAL | Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity. |
| Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab | ACTIVE_COMPARATOR | Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m\^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m\^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m\^2 every 4 weeks (Q4W) or 70 mg/m\^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m\^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m\^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6. |
| V-Exposed | EXPERIMENTAL | Venetoclax Exposed: Treatment with Pirtobrutinib+Venetoclax+Obinutuzumab Q4W |
| V-Naive | EXPERIMENTAL | Venetoclax Naive: Treatment with Pirtobrutinib+Venetoclax+Obinutuzumab Q4W |
| Treatment Arm | EXPERIMENTAL | In this single-arm study, patients will receive 200mg of pirtobrutinib once daily on Day 1-28 of each 28-day cycle. |
| Pirtobrutinib Standard Dose (Dose 1)-Part 1 | ACTIVE_COMPARATOR | Pirtobrutinib administered orally. |
| Pirtobrutinib Dose 2-Part 1 | EXPERIMENTAL | Pirtobrutinib administered orally. |
| Pirtobrutinib Dose 3-Part 1 | EXPERIMENTAL | Pirtobrutinib administered orally. |
| Pirtobrutinib Standard Dose-Part 2 | EXPERIMENTAL | Pirtobrutinib administered orally. |
| Pirtobrutinib-Obinutuzumab | EXPERIMENTAL | Eligible participants will receive initial treatment with pirtobrutinib and obinutuzumab for 12 cycles. Participants with progressive chronic lymphocytuc leukemia or small lymphocytic lymphoma during the off-treatment follow-up will receive continuous pirtobrutinib monotherapy. |
| Phase I Dose Escalation (Pirtobrutinib Monotherapy) | EXPERIMENTAL | Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 3 | EXPERIMENTAL | CLL/SLL patients with no prior therapy. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 1 | EXPERIMENTAL | Non-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 4 | EXPERIMENTAL | CLL/SLL patients treated with prior therapy, BTK inhibitor naïve. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 2 | EXPERIMENTAL | CLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 5 | EXPERIMENTAL | WM patients treated with a prior BTK inhibitor-containing regimen. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 6 | EXPERIMENTAL | MZL patients treated with a prior BTK inhibitor-containing regimen. |
| Phase 2 (Pirtobrutinib Monotherapy) Cohort 7 | EXPERIMENTAL | Defined as CLL/SLL or NHL not otherwise specified in Cohorts 1 through 6, inclusive of CLL/SLL, Richter's transformation, or low grade NHL with transformation, blastoid MCL, and patients with history of CNS involvement or primary CNS lymphoma. In the event the Sponsor electively closes Cohorts 2-4 prior to completion, patients with CLL/SLL who are ineligible to participate in or unable to access late phase studies of pirtobrutinib may be eligible to enroll in this cohort Diffuse large B-cell lymphoma (DLBCL) is excluded. MCL without prior BTK inhibitor treatment is excluded. Patients enrolling to Cohort 7 must have received one or more prior therapies or have no available approved therapy with demonstrated clinical benefit with the exception of untreated Richter's transformation, which is allowed. |
| Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm A | EXPERIMENTAL | Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax |
| Phase 1b Dose Expansion (Pirtobrutinib Combination Therapy) Arm B | EXPERIMENTAL | Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab |
| Phase 1 Dose Expansion (Pirtobrutinib Monotherapy) | EXPERIMENTAL | Patients to receive the recommended Phase 2 dose of pirtobrutinib |
| Name | Type | Description |
|---|---|---|
| Pirtobrutinib | DRUG | Administered orally. |
| Ibrutinib | DRUG | Administered orally. |
| Bendamustine | DRUG | IV |
| Rituximab | DRUG | IV |
| Venetoclax | DRUG | Oral |
| Idelalisib | DRUG | Oral |
| Obinutuzumab | DRUG | Given IV 100mg day 1, 900 mg day 2, 100mg days 8, 15 |
Inclusion Criteria: * Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria * Part 1 - Known 17p deletion status (wildtype or deleted). Part 2 - Must have deletion of 17p as determined by FISH testing * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 * Adequate o...