Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Heart and Blood Diseases

Rare Diseases

Lymphoma

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Lymphoma, Mantle-Cell

Lymphoma, Follicular

Lymphoma, B-Cell, Marginal Zone

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Waldenstrom Macroglobulinemia

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphoma, Non-Hodgkin

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphosarcoma

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Mantle Cell Lymphoma

Follicular Lymphoma

B-cell Lymphoma

Marginal Zone Lymphoma

Diffuse Large B-Cell Lymphoma

Primary Central Nervous System Lymphoma

Richter Syndrome

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Amino Acids

Venetoclax

Acalabrutinib

Zanubrutinib

Rituximab

Pirtobrutinib

Ibrutinib

Idelalisib

Antineoplastic Agents, Immunological

Immunologic Factors

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Dose Escalation and determination of MTD; multiple dose levels of pirtobrutinib to be evaluated

Non-blastoid MCL patients treated with a prior BTK-inhibitor containing regimen.

CLL/SLL patients treated with prior therapy, BTK inhibitor naïve.

CLL/SLL patients treated with 2 or more prior regimens, including a BTK inhibitor-containing regimen.

WM patients treated with a prior BTK inhibitor-containing regimen.

MZL patients treated with a prior BTK inhibitor-containing regimen.

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.

Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax

Relapsed/Refractory CLL will receive the recommended Phase 2 dose of pirtobrutinib in combination with venetoclax and rituximab

Patients to receive the recommended Phase 2 dose of pirtobrutinib

Donald Tsai, MD, PhD

This is an open-label, multi-center Phase 1/2 study of oral LOXO-305 (pirtobrutinib) in patients with CLL/SLL and NHL who have failed or are intolerant to standard of care.

This study includes 3 parts: Phase 1 (pirtobrutinib monotherapy dose escalation and dose expansion), Phase 1b (pirtobrutinib combination therapy dose expansion), and Phase 2 (pirtobrutinib monotherapy dose expansion). In Phase 1, patients will be enrolled using an accelerated titration design. The starting dose of pirtobrutinib in oral tablet form is 25 mg/day (e.g., 25 mg once daily \[QD\]). Once the MTD and/or RP2D is identified in Phase 1 dose escalation, enrollment will continue to Phase 1 dose expansion and can commence to Phase 1b (Arms A and B). For Phase 2, patients will be enrolled to one of seven Phase 2 dose expansion cohorts depending on tumor histology and prior treatment history. Cycle length will be 28 days.

A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL

A Phase 1/2 Study of Oral LOXO-305 in Patients With Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or Non-Hodgkin Lymphoma (NHL)

Individual EORTC symptom scores range from 1 (not at all) to 4 (very much) with higher scores representing more severe symptom severity.

EORTC physical function item scores range from 1 (not at all) to 4 (very much) with higher scores indicating poorer functioning.The total EORTC physical functioning score ranges from 0-100 where a higher score indicates higher/healthier level of functioning.

Eli Lilly and Company

Loxo Oncology, Inc.

Obinutuzumab

Dose Escalation:

Participants will receive a single dose of tirabrutinib on Day 1 of Cycle 1 and tirabrutinib 20 mg + idelalisib 50 mg on Day 2 and remainder of Cycle 1. For all subsequent cycles, participants will receive tirabrutinib 20 mg + idelalisib 50 mg. Based on DLTs observed in subsequent cohorts, additional participants will be enrolled and administered escalating dose of tirabrutinib up to 160 mg + idelalisib up to 100 mg to determine the maximum tolerated dose (MTD) of tirabrutinib either once daily or twice daily.

Dose Expansion:

Additional participants will receive tirabrutinib + idelalisib for an additional 6 years from the date of Protocol Amendment 8.

Dose Escalation:

Participants will receive a single dose of tirabrutinib 40 mg on Day 1 of Cycle 1 and tirabrutinib 40 mg + entospletinib 200 mg on Day 2 and remainder of Cycle 1. For all subsequent cycles, participants will receive tirabrutinib 40 mg + entospletinib 200 mg. Based on DLTs observed in subsequent cohorts, additional participants will be enrolled and administered escalating dose of tirabrutinib up to 160 mg + entospletinib up to 400 mg to determine the maximum tolerated dose (MTD) of tirabrutinib either once daily or twice daily.

Dose Expansion:

Additional participants will receive tirabrutinib + entospletinib for an additional 6 years from the date of Protocol Amendment 8.

Dose escalation:

Participants will receive tirabrutinib + idelalisib + obinutuzumab 1000 mg at 8 doses (tirabrutinib and idelalisib doses will depend on results of Combination I data). Based on DLTs observed, additional participants will be enrolled to determine the maximum tolerated dose (MTD) of tirabrutinib either once daily or twice daily.

Dose Expansion:

Additional participants will receive tirabrutinib + idelalisib + obinutuzumab for an additional 6 years from the date of Protocol Amendment 8.

Dose escalation:

Participants will receive tirabrutinib + entospletinib + obinutuzumab 1000 mg at 8 doses (tirabrutinib and entospletinib doses will depend on results of Combination II data). Based on DLTs observed, additional participants will be enrolled to determine the maximum tolerated dose (MTD) of tirabrutinib either once daily or twice daily.

Dose Expansion:

Additional participants will receive tirabrutinib + idelalisib + obinutuzumab for an additional 6 years from the date of Protocol Amendment 8.

Participants with relapsed or refractory chronic lymphocytic leukemia (CLL) may be enrolled to receive tirabrutinib 80 mg once daily.

Tirabrutinib

Entospletinib

Gilead Study Director

The primary objectives of this study are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of tirabrutinib (ONO/GS-4059) in combination with other targeted anti-cancer therapies and to evaluate the long-term safety of tirabrutinib as a monotherapy and in combination with other targeted anti-cancer therapies in adults with relapsed or refractory B-cell lymphoproliferative malignancies.

This study consists of three parts: Dose Escalation, Dose Expansion, and Long-term Safety Monitoring. During the Dose Escalation phase, participants will be sequentially enrolled in a standard 3 + 3 dose escalation study design, to receive oral tirabrutinib combined with idelalisib entospletinib +/- obinutuzumab. The Dose Expansion Phase will enroll additional participants with a single B-cell lymphoproliferative malignancy disease type to further evaluate efficacy, safety, tolerability, PK, and pharmacodynamics. The Long-term Safety Monitoring phase will evaluate the long-term safety of tirabrutinib both as a monotherapy and in combination with other anti-cancer therapies. As of Amendment 9, all participants currently on the study who have no clinical evidence of disease progression will transition into long-term safety monitoring. Participants from the ongoing Study GS-US-401-1787 and participants who came off Study GS-US-401-1757 and Study GS-US-401-1787 but continued to receive treatment via named patient use (or individual expanded use) will be enrolled into the long-term safety monitoring group (Group VI). Participants enrolled in Group VI will continue the same treatment regimen in Study GS-US-401-1787 or named patient use (or individual expanded use). As of Protocol Amendment 8, the maximum treatment duration for any participant is an additional 6 years from the date of this amendment (ie. until November 2025). As of Amendment 9, entospletinib will be provided until 31 December 2020 to participants who are currently receiving entospletinib. Participants treated with entospletinib as part of a combination regimen with tirabrutinib will stop receiving entospletinib by 31 December 2020 but may continue to be treated with tirabrutinib monotherapy. Idelalisib will be provided as 50 mg tablets until 31 December 2020 and 100 mg tablets until study completion. Participants assigned to the 50 mg tablet will be given the option, at the investigator's discretion, to switch to 100 mg once daily idelalisib dose.

Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies

A Phase 1b Dose Escalation and Dose Expansion Study of Tirabrutinib (ONO/GS-4059) in Combination With Other Targeted Anti-cancer Therapies in Subjects With B-cell Malignancies

Overall response rate (ORR) is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) as assessed by disease type.

PFS is defined as the interval from the start of the study therapy to the earlier of the first documentation of definite disease progression or death from any cause.

AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Cmax is defined as the maximum observed concentration of drug.

Gilead Sciences

Hematologic Neoplasms

Coagulants

Hemostatics

Phase I: Dose Escalation and determination of RP2D, multiple dose levels of nemtabrutinib to be evaluated (Up to approximately 22 months).

Relapsed/Refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) participants with at least 2 prior systemic therapies and previously treated with a covalent Bruton's tyrosine kinase inhibitor (BTKi) who must have a documented BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until progressive disease (PD), unacceptable adverse events (AEs), or discontinuation at investigator's discretion (up to approximately 64 months).

R/R CLL/SLL participants who have failed or were intolerant to a BTKi with documentation of the absence of BTK mutation on C481 residue receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Richter's transformation (RT) participants who have failed at least one prior therapy receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Follicular Lymphoma (FL) participants who have failed at least 2 prior systemic therapies and are histology grade 1, 2, or 3A receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Mantle Cell Lymphoma (MCL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Marginal Zone Lymphoma (MZL) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

High-grade B-cell lymphoma (BCL) participants who have failed at least 2 prior systemic therapies and have known MYC and BCL2 and/or BCL6 translocations confirmed by flourescence in situ hybridization (FISH) or overexpression by immunohistochemistry (IHC) receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Waldenström macroglobulinemia (WM) participants who have failed at least 2 prior systemic therapies receive up to 65 mg of nemtabrutinib per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

B-cell Non-Hodgkin's lymphoma (NHL), CLL/SLL and WM participants receive up to 65 mg of nemtabrutinib fasted (1 hour prior to or 2 hours after meal) and non-fasted per day orally in each cycle (Cycle length = 28 days) until PD, unacceptable AEs, or discontinuation at investigator's discretion (up to approximately 64 months).

Nemtabrutinib will be orally administered once per day under fasted conditions (1 hour prior to or 2 hours after a meal) and is available in tablets in strengths of 5 mg or 20 mg. For Expansion Food Effect Cohort I, nemtabrutinib will be orally administered once per day under fasted and non-fasted condition.

Nemtabrutinib

Medical Director

This study aims to evaluate the safety, tolerability, pharmacodynamic, and pharmacokinetic (PK) of nemtabrutinib (formerly ARQ 531) tablets in selected participants with relapsed or refractory hematologic malignancies. No formal hypothesis testing will be performed for this study.

This study includes 2 parts: Phase 1 (dose escalation) and Phase 2 (dose expansion). In Phase 1, participants will enroll using 3+3 dose escalation design. The starting dose of nemtabrutinib in oral tablet form was 5mg/day continuously. Dose escalation will continue until the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) and dosing schedule is reached based on protocol-defined dose limiting toxicity (DLT). After the determination of the RP2D, 9 expansion cohorts will be initiated to evaluate the safety, tolerability, and efficacy of nemtabrutinib at RP2D in participants with specifically defined disease.

Single group assignment (definition : A type of intervention model describing a clinical trial in which all participants receive the same intervention/treatment.)

A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)

A Phase 1/2 Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Activity of ARQ 531 in Selected Subjects With Relapsed or Refractory Hematologic Malignancies

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

DLT is defined by the occurrence of any of the following treatment emergent adverse event (TEAE) unless unequivocally due to the underlying malignancy or an extraneous cause within the first 28 days of study treatment (for dose escalation only) and graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Any Grade 5 TEAE, any Grade 3 nonhematological TEAE except alopecia, nausea, vomiting, diarrhea, and transient Grade 3 laboratory abnormalities which recover within 1 week without intervention, any Grade 3 hematological TEAE that does not recover to Grade 1 or baseline within 7 days with the exception of Grade 3 lymphocytosis, which is considered to be an expected outcome of BTK inhibition, any Grade 4 nonhematological and hematological TEAE, or any other toxicity that in the view of the investigator represents a clinically significant hazard to the participant.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued study treatment due to an AE will be reported.

ORR is defined as the percentage of participants achieving a best overall response of complete response (CR), partial response (PR) or partial response with lymphocytosis (PRL). iwCLL criteria as assessed by the investigator. CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.

ORR is defined as percentage of participants achieving best overall response of CR/PR per Lugano classification as assessed by investigator. CR defined as EITHER CR by imaging (computed tomography \[CT\]): all lymph nodes normal (none ≥15 mm) \& normal liver, spleen OR complete metabolic response (CMR): score of 1, 2 or3 on 5-point scale assessing fluorodeoxyglucose (FDG) metabolic activity in lymphomatous lesions (range: 1=no uptake above background to 5=uptake markedly higher than liver) AND bone marrow (BM) normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in sum of product of diameters \[SPD\] of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR Partial Metabolic Response (PMR) with score of 4/5 on FDG 5-point scale (with no new lesions) \& decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.

Blood samples will be collected at prespecified time points to determine Tmax of nemtabrutinib.

Blood samples will be collected at prespecified time points to determine Cmax of nemtabrutinib.

Blood samples will be collected at prespecified time points to determine AUC 0-24hrs of nemtabrutinib.

t1/2 is the time it takes for the concentration of nemtabrutinib in the body to decrease by half during the elimination phase.

DOR is defined as the time from the first documented evidence of CR or PR (or PRL for CLL/SLL participants) until progressive disease or death due to any cause, whichever occurs first. CR is defined as meeting the following criteria: no lymph nodes \>1.5 cm, spleen size \<13 cm, liver normal; no constitutional symptoms, normal lymphocyte count, platelets ≥100 x 10\^9/L; hemoglobin ≥11 g/dL; and normocellular marrow (no CLL cells or B lymphoid nodules). PR is defined as ≥50% decrease in ≥2 of the following: lymph nodes, liver and/or spleen size, lymphocytes PLUS ≥1 of the following met: platelets ≥100 x 10\^9/L or ≥50% increase from screening, hemoglobin \>11 g/dL or ≥50% increase from screening, CLL cells or B lymphoid nodules in marrow.

DOR is defined as time from first documented evidence of CR/PR (or PRL for CLL/SLL participants) until progressive disease or death due to any cause, whichever occurs first. CR defined as EITHER CR by imaging (computed tomography \[CT\]): all lymph nodes normal (none ≥15 mm) \& normal liver, spleen OR complete metabolic response (CMR): score of 1, 2 or3 on 5-point scale assessing FDG metabolic activity in lymphomatous lesions (range: 1=no uptake above background to 5=uptake markedly higher than liver) AND BM normal by morphology. PR defined as EITHER PR by imaging (CT) with ≥50% decrease in SPD of target lesions, no worsening of nontarget lesions, no new lesions and ≥50% spleen abnormal portion OR PMR with score of 4/5 on FDG 5-point scale (with no new lesions) \& decreased overall uptake AND residual BM abnormalities; OR CR by imaging with residual BM abnormalities; OR PR by imaging without residual BM abnormalities.

ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)

Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks.

Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) once daily + idelalisib 100 mg (1 x 100 mg tablet) once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.

The primary objective of this study is to determine the preliminary efficacy of the combination of tirabrutinib and idelalisib with obinutuzumab in adults with relapsed or refractory chronic lymphocytic leukemia (CLL).

The study has a 6 participant per arm safety run-in to evaluate safety prior to the enrollment of subsequent participants. The treatment period is adaptive, with a duration of active treatment up to two years and a total follow-up on study for up to 30 days post end of treatment, or up to Week 25 should a participant discontinue treatment prior to Week 25 for reasons other than disease progression.

Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (GS-4059) and Idelalisib With and Without Obinutuzumab in Subjects With Chronic Lymphocytic Leukemia

Rate of CR per modified IWCLL 2008 criteria at Week 25 was defined as the percentage of participants who achieved CR/complete remission with incomplete recovery of the bone marrow (CRi) at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity.

Rate of CR/BM MRD at Week 25 was defined as percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved BM MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with four-color-flow cytometry (FACS) and MRD negativity was defined as one CLL cell per 10,000 leukocytes \[0.01%\], ie,\<10\^-4 and participants were defined as MRD negative if their disease burden was below this threshold.

Rate of CR/PB MRD at Week 25 was defined as the percentage of participants who achieved CR/CRi per modified IWCLL 2008 criteria and also achieved PB MRD negativity at Week 25. CR: meeting following criteria and no disease related symptoms: no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow sample must be normocellular with 30% lymphocytes and no B-lymphoid nodules; platelets \> 100,000/µL; hemoglobin \> 11 g/dL; and neutrophils \> 1500/µL. CRi: CR criteria (no lymphadenopathy \> 1.5 cm/hepatomegaly/splenomegaly; lymphocytes \< 4000/μL; bone marrow \[hypocellular\] with 30% lymphocytes and no B-lymphoid nodules), persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. MRD response was assessed with FACS and MRD negativity was defined as one CLL cell per 10,000 leukocytes \[0.01%\], ie,\<10\^-4 and participants were defined as MRD negative if their disease burden was below this threshold.

ORR was assessed based on modified IWCLL 2008 criteria and was defined as percentage of participants achieving a CR, CRi, partial remission (PR; including nodular partial response \[nPR\]), and PR with lymphocytosis (PR-L). CR and CRi: meeting all the criteria that have been defined in Outcome measures 1, 2 and 3. PR: ≥ 2 of these: ≥ 50% decrease in lymphocytes, lymphadenopathy, size of liver, size of spleen, and 50% decrease in bone marrow infiltrates; and ≥ 1 of these: neutrophils \> 1500/μL or ≥ 50% increase from Baseline, platelets ≥ 100,000/µL or ≥ 50% increase from Baseline, hemoglobin \>11 g/dL or ≥ 50% increase from Baseline. PR-L: meeting PR criteria; however, a lymphocytosis related to treatment may be present. nPR: All criteria for a CR/CRi were fulfilled, but the bone marrow showed lymphoid nodules.

Treatment-emergent AEs are defined as 1 or both of the following:

* Any AEs with an onset date on or after the study drug start date and no later than 30 days after permanent discontinuation of study drug
* Any AEs leading to discontinuation of study drug

A SAE is defined as an event that, at any dose, resulted in any of the following: death, life-threatening, in-patient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, a congenital anomaly/birth defect, or a medically important event or reaction.

German CLL Study Group

Adverse Events: The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.

All-Cause Mortality: The All Enrolled Analysis Set included all participants who received a study participant identification number in the study after screening.

Tirabrutinib 80 mg (4 x 20 mg tablets/2 x 40 mg tablets/1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks.

Tirabrutinib + Idelalisib

Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses administered intravenously over 21 weeks.

Tirabrutinib + Idelalisib + Obinutuzumab

Tirabrutinib 80 mg (4 x 20 mg tablets/ 2 x 40 mg tablets/ 1 x 80 mg tablet) orally once daily + idelalisib 100 mg (1 x 100 mg tablet) orally once daily for up to 104 weeks + obinutuzumab 100 mg on Day 1, 900 mg on Day 1 or 2, and 1000 mg subsequently for up to 8 doses on Day 1 of Weeks 2, 3, 5, and then every 4 weeks through Week 21.

Total

Age, Continuous

Sex: Female, Male

Race

Not Permitted = local regulators did not allow collection of race information.

Race/Ethnicity, Customized

Ethnicity

Not Permitted = local regulators did not allow collection of ethnicity information.

The Full Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.

Gilead Clinical Study Information Center

Rate of Complete Response/Complete Remission (CR), as Assessed by Investigator Using Modified International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria at Week 25

Participants in the Full Analysis Set were analyzed.

Rate of CR With Bone Marrow Minimal Residual Disease (CR/BM MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25

Rate of CR With Peripheral Minimal Residual Disease (CR/PB MRD) Negativity, as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25

Overall Response Rate (ORR), as Assessed by the Investigator Using the Modified IWCLL 2008 Criteria at Week 25

Any Treatment-Emergent AEs

Treatment-Emergent SAEs

The Safety Analysis Set included all randomized or enrolled participants who received at least 1 dose of any study drug.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL	NCT03740529	Chronic Lymphoc... Waldenstrom Mac... Mantle Cell Lym... Marginal Zone L... B-cell Lymphoma Small Lymphocyt...	Pirtobrutinib Venetoclax Rituximab	18 Years -	Eli Lilly and Company
Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies	NCT02457598	B-cell Malignan...	Tirabrutinib Idelalisib Entospletinib Obinutuzumab	18 Years -	Gilead Sciences
A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)	NCT03162536	Lymphoma, B-Cel... Small Lymphocyt... Chronic Lymphoc... Waldenstrom Mac... Mantle Cell Lym... Diffuse Large B... Richter's Trans... Follicular Lymp... Marginal Zone L...	Nemtabrutinib	18 Years -	ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
A Study of Nemtabrutinib (MK-1026) in Participants With Relapsed or Refractory Hematologic Malignancies (ARQ 531-101/MK-1026-001)	NCT03162536	Lymphoma, B-Cel... Small Lymphocyt... Chronic Lymphoc... Waldenstrom Mac... Mantle Cell Lym... Diffuse Large B... Richter's Trans... Follicular Lymp... Marginal Zone L...	Nemtabrutinib	18 Years -	ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Study to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib and Idelalisib With and Without Obinutuzumab in Adults With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)	NCT02968563	Chronic Lymphoc...	Tirabrutinib Idelalisib Obinutuzumab	18 Years -	Gilead Sciences
A Study of Oral LOXO-305 in Patients With Previously Treated CLL/SLL or NHL	NCT03740529	Chronic Lymphoc... Waldenstrom Mac... Mantle Cell Lym... Marginal Zone L... B-cell Lymphoma Small Lymphocyt...	Pirtobrutinib Venetoclax Rituximab	18 Years -	Eli Lilly and Company
Dose Escalation and Dose Expansion Study of Tirabrutinib in Combination With Other Targeted Anti-cancer Therapies in Adults With B-cell Malignancies	NCT02457598	B-cell Malignan...	Tirabrutinib Idelalisib Entospletinib Obinutuzumab	18 Years -	Gilead Sciences

Spots Global Cancer Trial Database for tirabrutinib

Every month we try and update this database with for tirabrutinib cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.