Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as [14C]-LOXO-305, LY3527727, Pirtobrutinib
LOXO-305 · 18 trials · 23 indications
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
PFS, as assessed by IRC, is defined as the time from randomization until documented disease progression as per iwCLL (International Workshop on Chronic Lymphocytic Leukemia) 2018 criteria, or death from any cause, whichever occurs first.
Assessed by blinded independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018
Assessed per Lugano criteria
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.
To determine the safety and tolerability of mosunetuzumab in combination with pirtobrutinib.
To determine the efficacy of the combination of mosunetuzumab and pirtobrutinib.
Will report the number of CR and the estimated CR rate with 95% exact binomial confidence interval (CI). Will build logistic regression to evaluate the risk factor association with the endpoint of interest.
Analyses will follow standard methodology by employing Kaplan-Meier (KM) and Cox proportional hazard model methodology. The 1-year PFS rate and 95% CI will be estimated by KM.
To assess the activity of Pirtobrutinib in combination with rituximab (P-R) as a therapeutic alternative to immunochemotherapy (R-Bendamustine or R-CHOP regimen) in patients with an indolent clinical presentation of MCL. The primary objective will be assessed by the complete remission rate (CRR), defined as the percentage of patients who achieve a complete response (CR) at the end of Cycle 6 of the P-R combination according to the Lugano Classification.
To assess the ORR in the study population at Cycle 7.
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.
The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. AEs and clinically significant laboratory abnormalities meeting grade 3 4 or 5 will be summarized by maximum intensity and relationship to study drug for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days.
CR will be defined as the proportion of treated participants who experience a CR per Lugano criteria among evaluable participants. The Lugano classification recommends the Deauville five-point scale for reporting response by Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computerized tomography (CT): (1) no uptake or no residual uptake (when used interim) (2) slight uptake, but below blood pool (mediastinum) (3) uptake above mediastinal, but below or equal to uptake in the liver (4) uptake slightly to moderately higher than liver (5) markedly increased uptake or any new lesion (on response evaluation) from cycle 5 Day 1 through the follow-up period up to 94 weeks.
The proportion of participants with a diagnosed incident of CRS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.
The proportion of participants with a diagnosed incident of ICANS for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.
The proportion of participants with a diagnosed incident of HLH for the first 6 participants from the initiation of the study drug combination (Cycle 2 Day 8 (C2D8)) through the end of cycle 2 (Cycle 2 Day 21 (C2D21)), approximately 14 days, and graded according to the American Society of Transplantation and Cellular Therapy (ASTCT) criteria will be reported.
Defined by the 2018 International Workshop on Chronic Lymphocytic Leukemia (IWCLL) guidelines
Best Complete Response (CR) rate is defined as the proportion of participants achieving CR at any of the 3 timepoints (after 4, 8 and 12 cycles). CR is defined per Lugano 2014 criteria.
VGPR or better response rate is defined as proportion of participants experienced VGPR or complete response (CR) based on modified 6th International Workshop on WM \[IWWM\] criteria (NCCN 2014).
ORR was assessed by an Independent Review Committee (IRC). It was estimated based on the percentage of participants with best overall response (BOR) of complete response (CR) or partial response (PR). Two-sided 95% CI was calculated using the exact binomial distribution. PAS consisted of participants with Central histologically confirmed non-blastoid MCL, with no CNS metastases and treated with prior chemoimmunotherapy and BTK inhibitor-containing regimen, measurable disease at baseline as assessed using Lugano criteria, and have received at least 1 dose of study drug.
A summary of TEAEs and SAEs regardless of causality, will be reported in the Reported Adverse Events module
DLTs of Pirtobrutinib
Blood Pressure, Pulse Rate, and Body Temperature
Hematology, Clinical Chemistry, Urinalysis, Pregnancy, Hepatitis Serology and Cytomegalovirus (CMV)
ECG QT Interval
Stable platelet response rate is defined as the proportion of participants achieving platelet count of greater than or equal to 50 thousand per microliter (k/μL) and on at least 4 of the 6 consecutive biweekly visits between weeks 14 and 24 in the absence of rescue therapy and prohibited concomitant medication that may impact efficacy
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 Part 1 | ACTIVE_COMPARATOR | Participants will receive ibrutinib orally. |
| Pirtobrutinib Part 2 | EXPERIMENTAL | Participants will receive pirtobrutinib orally. |
| Arm A - Pirtobrutinib | EXPERIMENTAL | Participants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity. |
| Arm B - Bendamustine Plus Rituximab | ACTIVE_COMPARATOR | Participants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD). |
| 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 | Orally |
| Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) | ACTIVE_COMPARATOR | Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country. |
| 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. |
| Dosing Strategy 1-Mosunetuzumab and Pirtobrutinib | EXPERIMENTAL | Participants receive pirtobrutinib daily on days 1-21 of 21 day cycles. Mosunetuzumab will be administered subcutaneously starting on cycle 2, day 1. If patients have a complete response to treatment, after 9 cycles, they will continue with on pirtobrutinib for a total of 18 cycles. If patients receive a very good partial or minor response, they will continue to receive Mosunetuzumab and Pirtobrutinib for a total of 18 cycles. |
| Dosing Strategy 2- Mosunetuzumab and Pirtobrutinib | EXPERIMENTAL | Participants receive pirtobrutinib daily on days 1-21 of 21 day cycles. Mosunetuzumab will be administered subcutaneously starting on cycle 3, day 1. If patients have a complete response to treatment, after 9 cycles, they will continue with on pirtobrutinib for a total of 19 cycles. If patients receive a very good partial or minor response, they will continue to receive Mosunetuzumab and Pirtobrutinib for a total of 19 cycles. |
| Treatment (pirtobrutinib, mosunetuzumab) | EXPERIMENTAL | Patients receive pirtobrutinib PO QD on 7 days prior to the start of mosunetuzumab (day -7) and continue it until up to 52 weeks. Patients receive mosunetuzumab subcutaneously (SC) or intravenously (IV) on days 1, 8, and 15 of cycle 1 then on day 1 of remaining cycles. Cycles of mosunetuzumab repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients with a CR after cycle 8 discontinue mosunetuzumab. Patients also undergo blood sample and oral swab and/or rectal swab collection, tissue biopsy, CT, and PET/CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy at screening and after cycle 8. |
| Pirtobrutinib with rituximab | EXPERIMENTAL | Patients will receive a P-R combination for at least 24 cycles (C24). The first cycle of P-R will be administered at day 1 (baseline) . Pirtobrutinib discontinuation will be decided after C24, according to the MRD response and the TP53 mutational status. Rituximab treatment will end up at C23. |
| Pirtobrutinib | EXPERIMENTAL | Pirtobrutinib administered orally. |
| Rituximab+Pirtobrutinib, Pirtobrutinib Alone | EXPERIMENTAL | This arm included participants who had a complete response to Rituximab and Pirtobrutinib in Stage 1. In Stage 1, all participants will receive Rituximab and Pirtobrutinib for 6 Cycles (42 days). In Stage 2, subjects who experience a complete response will discontinue rituximab and continue treatment with pirtobrutinib only for 6 additional cycles. Participants in this arm will not have Stage 3 treatment. After completing Stage II treatment, subjects will discontinue treatment and proceed to End of Treatment (EOT) and Long-Term Follow-Up (LTFU) visits. |
| Rituximab+Pirtobrutinib, Continuded Rituximab+Pirtobrutinib, Pirtobrutinib Alone (6 Cycles) | EXPERIMENTAL | This arm included participants who had a Partial Response or Stable Disease response to Rituximab and Pirtobrutinib in Stage 1 and a Complete Response to continued Rituximab and Pirtobrutinib in Stage 2. In Stage 1, all participants will receive Rituximab and Pirtobrutinib for 6 Cycles (42 days). In Stage II, subjects who experienced a Partial Response or Stable Disease will continue Rituximab and Pirtobrutinib treatment for 6 additional cycles. In Stage III, subjects who experienced a Complete Response will discontinue rituximab and continue treatment with Pirtobrutinib only for 6 additional cycles. After completing Stage III treatment, subjects will discontinue treatment and proceed to End of Treatment (EOT) and Long-Term Follow-Up (LTFU) visits. |
| Rituximab+Pirtobrutinib, Continuded Rituximab+Pirtobrutinib, Pirtobrutinib Alone (24 Cycles) | EXPERIMENTAL | This arm included participants who had a Partial Response or Stable Disease response to Rituximab and Pirtobrutinib in Stage 1 and a Progressive Disease after continued Rituximab and Pirtobrutinib in Stage 2. In Stage I, all participants will receive Rituximab and Pirtobrutinib for 6 Cycles (42 days). In Stage II, subjects who experience a Partial Response or Stable Disease will continue Rituximab and Pirtobrutinib treatment for 6 additional cycles. In Stage III, subjects who experience Progressive Disease will discontinue treatment and proceed to End of Treatment (EOT) and Long-Term Follow-Up (LTFU) visits. |
| Rituximab+Pirtobrutinib, Continuded Rituximab+Pirtobrutinib | EXPERIMENTAL | This arm included participants who had a Partial Response or Stable Disease response to Rituximab and Pirtobrutinib in Stage 1 and a Partial Response or Stable Disease to continued Rituximab and Pirtobrutinib in Stage 2. In Stage I, all participants will receive Rituximab and Pirtobrutinib for 6 Cycles (42 days). In Stage II, subjects who experience a Partial Response or Stable Disease will continue Rituximab and Pirtobrutinib treatment for 6 additional cycles. In Stage III, subjects who experience a Partial Response or Stable Disease will discontinue rituximab and continue treatment with Pirtobrutinib only until progression or other treatment discontinuation criteria are met. After progression or other treatment discontinuation criteria are met, subjects will discontinue treatment and proceed to End of Treatment (EOT) and Long-Term Follow-Up (LTFU) visits. |
| Rituximab+Pirtobrutinib Only | EXPERIMENTAL | This arm included participants who had Progressive Disease after Rituximab and Pirtobrutinib treatment in Stage 1. In Stage 1, all participants will receive Rituximab and Pirtobrutinib for 6 Cycles (42 days). If participants had Progressive Disease after Stage I, they will not have Stage II or Stage III of treatment. After completing Stage I treatment, subjects will discontinue treatment and proceed to End of Treatment (EOT) and Long-Term Follow-Up (LTFU) visits. |
| 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. |
| Treatment (obinutuzumab, glofitamab, pirtobrutinib) | EXPERIMENTAL | Participants receive obinutuzumab IV on days 1 and 2 of cycle 1 for a total of 2 doses. Participants receive glofitamab IV on days 8 and 15 of cycle 1 and day 1 of remaining cycles. Cycles repeat every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Participants receive pirtobrutinib PO once a day (QD) starting on Cycle 2 Day 8. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity up to Cycle 30, Day 22. Participants also undergo FDG-PET/CT at screening, after every 4 cycles through cycle 13 and then after every 6 cycles. Participants will undergo a bone marrow biopsy and aspiration at cycle 13 and blood sample collection throughout study and a tissue biopsy at relapse or progression. |
| 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. |
| Monotherapy Cohort: Obinutuzumab and Glofitamab | ACTIVE_COMPARATOR | Study procedures will be conducted as follows: * Baseline visit with screening procedures, including bone marrow biopsy and Positron Emission Tomography (PET) or Computed Topography (CT) scans. * PET/CT scans after 4, 8, and 12 cycles of therapy and at 6 and 15 months after end-of-treatment. * Cycle 1: * Day 1, 2, and 7 of 21- day Cycle: Predetermined dose of Obinutuzumab 1x daily. * Day 8 and 15 of 21- day Cycle: Predetermined dose of Glofitamab 1x daily. Hospitalization will be required for initial dose and post-dose observation. * Cycle 2 - 12 --Day 1 of 21-day Cycle: Predetermined dose of Glofitamab 1x daily. Hospitalization will be required for second dose and post-dose observation * End of treatment visit. * Follow up visits: for months 10 - 24, visits will be every 3 months. For months 25 - 60 visits will be every 6 months. * After completion of a 10-patient safety lead-in cohort, enrollment will open to the other two cohorts. |
| Combination A Group: Obinutuzumab, Glofitamab, and Polatuzumab Vedotin | EXPERIMENTAL | Study procedures will be conducted as follows: * Baseline visit with screening procedures, including bone marrow biopsy and PET/CT scans. * PET/CT scans after 4, 8, and 12 cycles of therapy and at 6 and 15 months after end-of-treatment. * Cycle 1: * Day 1, 2, and 7 of 21- day Cycle: Predetermined dose of Obinutuzumab 1x daily. * Day 8 and 15 of 21- day Cycle: Predetermined dose of Glofitamab 1x daily. Hospitalization will be required for initial dose and post-dose observation. * Cycle 2 - 7: \- Day 1 of 21-day Cycle: Predetermined dose of Glofitamab 1x daily. Predetermined dose of Polatuzumab Vedotin 1x daily. * Cycle 8 - 12 \- Day 1 of 21-day Cycle: Predetermined dose of Glofitamab 1x daily. * End of treatment visit. * Follow up visits: for months 10 - 24, visits will be every 3 months. For months 25 - 60 visits will be every 6 months. |
| Combination B Group: Obinutuzumab, Glofitamab, and Pirtobrutinib | EXPERIMENTAL | Study procedures will be conducted as follows: * Baseline visit with screening procedures, including bone marrow biopsy and PET/CT scans. * PET/CT scans after 4, 8, and 12 cycles of therapy and at 6 and 15 months after end-of-treatment. * Cycle 1: * Day 1, 2, and 7 of 21- day Cycle: Predetermined dose of Obinutuzumab 1x daily. * Day 8 and 15 of 21- day Cycle: Predetermined dose of Glofitamab 1x daily. Hospitalization will be required for initial dose and post-dose observation. * Cycle 2 - 12 \- Day 1 of 21-day Cycle: Predetermined dose of Glofitamab 1x daily. Predetermined dose of Pirtobrutinib 1x daily. Days 2-21 of each cycle: Pirtobrutinib will be taken once daily. * End of treatment visit. * Follow up visits: for months 10 - 24, visits will be every 3 months. For months 25 - 60 visits will be every 6 months. |
| Combination C Group: Obinutuzumab, Glofitamab, and Atezolizumab | EXPERIMENTAL | Study procedures will be conducted as follows: * Baseline visit with screening procedures, including bone marrow biopsy and PET/CT scans. * PET/CT scans after 4, 8, and 12 cycles of therapy and at 6 and 15 months after end-of-treatment. * Cycle 1: * Day 1, 2, and 7 of 21- day Cycle: Predetermined dose of Obinutuzumab 1x daily. * Day 8 and 15 of 21- day Cycle: Predetermined dose of Glofitamab 1x daily. Hospitalization will be required for initial dose and post-dose observation. * Cycle 2 - 12 \- Day 1 of 21-day Cycle: Predetermined dose of Glofitamab 1x daily. Predetermined dose of Atezolizumab 1x daily. * End of treatment visit. * Follow up visits: for months 10 - 24, visits will be every 3 months. For months 25 - 60 visits will be every 6 months. |
| PIRTOBRUTINIB + VENETOCLAX | EXPERIMENTAL | Participants will receive: * Standard of care bone marrow aspirate \& biopsy within 90 days of Cycle 1 Day 1. * Computed Tomography (CT) scan of chest, pelvis \& abdomen within 90 days of Cycle 1 Day 1. * Electrocardiogram at screening. * Cycle 1 * Electrocardiogram. * Day 1-28: Predetermined dose of Pirtobrutinib 1x daily. * Cycle 2 -Day 1-28: Predetermined dose Pirtobrutinib \& Venetoclax 1x daily. Tumor lysis syndrome (TLS) prophylaxis, predetermined dose Allopurinol at least 72 hrs prior to 1st administration of Venetoclax and dose escalation at Day 8 \& Day 15. * Cycles 3-24 * Day 1-28: Predetermined dose of Pirtobrutinib \& Venetoclax 1x daily. * Electrocardiogram: Cycles 3, 6, 9,12,15,18,21,24 * CT scan of chest, pelvis \& abdomen: Cycles 7, 13, End of Treatment if extramedullary disease at baseline unresolved in previous CT scan * Standard of care bone marrow aspirate and biopsy: Cycles 7, 13, End of Treatment * Follow up every 12 wks for 4 yrs. |
| LOXO-305 | EXPERIMENTAL | Participants received 200 mg of LOXO-305 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. |
| Pirtobrutinib Phase 1 | EXPERIMENTAL | Pirtobrutinib administered orally |
| Pirtobrutinib Phase 2 | EXPERIMENTAL | Pirtobrutinib administered orally |
| Placebo Phase 2 | PLACEBO_COMPARATOR | Placebo administered orally |
| 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 |
| Acalabrutinib | DRUG | Oral |
| Zanubrutinib | DRUG | Oral |
| Idelalisib | DRUG | Oral |
| Mosunetuzumab | DRUG | Administered subcutaneously on day one of applicable cycles. |
| Biospecimen Collection | PROCEDURE | Undergo blood sample and oral swab and/or rectal swab collection |
| Biopsy Procedure | PROCEDURE | Undergo tissue biopsy |
| Computed Tomography | PROCEDURE | Undergo CT and PET/CT |
| Positron Emission Tomography | PROCEDURE | Undergo PET/CT |
| Bone Marrow Aspiration | PROCEDURE | Undergo bone marrow aspiration and biopsy |
| Bone Marrow Biopsy | PROCEDURE | Undergo bone marrow aspiration and biopsy |
| Questionnaire Administration | OTHER | Ancillary studies |
| Pirtobrutinib and rituximab | DRUG | Patients will receive the study treatment (P-R combination) at day 1 (baseline) and during the treatment period (C24). Pirtobrutinib discontinuation per protocol will be decided after C24, according to the MRD response and the TP53 mutational status. Rituximab treatment will end up at C23. |
| Obinutuzumab | BIOLOGICAL | Given intravenously (IV) |
| Glofitamab | BIOLOGICAL | Given IV |
| Tumor Imaging | PROCEDURE | Undergo regular care imaging/scans |
| ClonoSeq Assay | DEVICE | ClonoSEQ is an FDA-cleared, Clinical Laboratory Improvement Amendments of 1988 (CLIA)-validated measure used to determine minimal residual disease (MRD). This helps uncover how much, if any, cancer remains in your body during and after treatment. |
| Polatuzumab Vedotin | DRUG | Antibody-drug conjugate, administered via intravenous infusion per protocol. |
| Atezolizumab | DRUG | Humanized immunoglobulin monoclonal antibody, administered via intravenous infusion per protocol. |
| Tocilizumab | DRUG | For the treatment of Cytokine Release Syndrome. Recombinant, humanized, anti-human monoclonal antibody, administered via intravenous infusion per protocol. |
| LOXO-305 | DRUG | Administered orally. |
| Placebo | DRUG | Administered orally |
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...
LOXO-305 is an investigational small molecule being studied for the treatment of lymphoid leukemia and related blood cancers. Its clinical development includes a Phase 2 trial in Chinese participants with blood cancers such as chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, and marginal zone lymphoma.
LOXO-305 targets BTK, which stands for Bruton's tyrosine kinase. BTK is an enzyme involved in signaling pathways that support the growth and survival of certain blood cancer cells. By binding to BTK, LOXO-305 is designed to interfere with that signaling.
LOXO-305 is being developed by Eli Lilly and Company, which trades on the New York Stock Exchange under the ticker LLY. The company is responsible for the clinical development program for this investigational BTK-targeted therapy.
LOXO-305 is in Phase 2 clinical development. It is an investigational drug and has not been approved by the FDA. The Phase 2 trial for LOXO-305 has been completed, and no active trials are currently listed for this asset.
LOXO-305 has been evaluated in one completed Phase 2 clinical trial, NCT04849416, titled A Study of LOXO-305 in Chinese Participants With Blood Cancer (Including Lymphoma and Chronic Leukemia). The trial enrolled 87 participants in China and was an uncontrolled, non-randomized study.
Yes, [14C]-LOXO-305 is an alternative name for LOXO-305. The [14C] label refers to a carbon-14 radiolabeled version of the molecule, which is used in certain research or clinical pharmacology studies. Both names refer to the same BTK-targeted investigational drug.