A Phase 3 interventional study of Rocbrutinib and Pirtobrutinib in CLL / SLL, CLL (Chronic Lymphocytic Leukemia) and CLL, Refractory, sponsored by Newave Pharmaceutical Inc. Recruiting at 7 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Newave Pharmaceutical Inc (part of Lupeng Pharmaceutical Ltd.) · Phase 3, Interventional, and Treatment
This is a Phase 3, randomized, open-label, multicenter study comparing rocbrutinib (LP-168) versus pirtobrutinib in adult participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton's tyrosine kinase inhibitor (cBTKi). Approximately 306 participants will be randomized 1:1 to receive rocbrutinib 200 mg orally once daily or pirtobrutinib 200 mg orally once daily, administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Randomization will be stratified by presence of del(17p)/TP53 mutation (yes/no), reason for discontinuation of prior cBTKi therapy (toxicity vs disease progression), prior exposure to a BCL2 inhibitor (yes/no), and region (United States/China/rest of world). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC) using iwCLL 2018 criteria for CLL and Lugano 2014 criteria for SLL. Key secondary objectives include overall survival, overall response rate, time-to-event outcomes, and safety/tolerability; exploratory objectives include health-related quality of life and biomarker assessments.
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are indolent B-cell malignancies characterized by accumulation of mature but dysfunctional lymphocytes. Covalent Bruton's tyrosine kinase inhibitors (cBTKis) have substantially improved outcomes for patients with CLL/SLL; however, disease progression on cBTKi therapy or intolerance leading to treatment discontinuation remains an important clinical challenge. Patients who discontinue cBTKi therapy due to progression have limited therapeutic options and may experience poor outcomes. Therefore, effective and well-tolerated therapies are needed for participants with relapsed or refractory (R/R) CLL/SLL who have previously received a covalent BTK inhibitor.
Rocbrutinib (LP-168) is a selective next-generation inhibitor of BTK, that can irreversibly inhibit WT BTK, and reversibly inhibit C481 mutated BTK, with activity against known resistance mutations for non-covalent BTKi, under investigation for the treatment of CLL/SLL. Pirtobrutinib is an oral BTK inhibitor with regulatory approval for adults with R/R CLL/SLL who have previously received a covalent BTK inhibitor (cBTKi). This Phase 3 study is designed to compare the efficacy and safety of rocbrutinib versus pirtobrutinib in adult participants with cBTKi-pretreated R/R CLL/SLL.
This is a Phase 3, randomized, open-label, multicenter study conducted at approximately 100 sites globally. Approximately 306 participants will be randomized in a 1:1 ratio to receive rocbrutinib (LP-168) or pirtobrutinib. Eligible participants are adults with confirmed R/R CLL or SLL who require therapy and have received prior treatment with a cBTKi. Participants may have received additional prior systemic therapies, including prior exposure to a BCL2 inhibitor. Key exclusion criteria include central nervous system involvement by CLL/SLL and clinically significant cardiovascular conditions, including uncontrolled arrhythmias and clinically relevant QTc prolongation.
Participants randomized to the investigational arm will receive rocbrutinib 200 mg orally once daily. Participants randomized to the active comparator arm will receive pirtobrutinib 200 mg orally once daily. Study treatments will be administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. Crossover between treatment arms is not permitted.
Randomization will be stratified based on prognostic and treatment-history factors, including: (1) del(17p) and/or TP53 mutation status, (2) reason for discontinuation of prior cBTKi therapy, (3) prior exposure to a BCL2 inhibitor, and (4) geographic region.
The primary endpoint is progression-free survival (PFS). PFS will be assessed by an independent review committee (IRC) to provide objective evaluation of disease status. Response and progression for participants with CLL will be assessed according to iwCLL 2018 criteria, while participants with SLL will be assessed using Lugano 2014 criteria.
Key secondary efficacy endpoints include overall survival (OS), overall response rate (ORR), duration of response (DOR), time to next treatment (TTNT), and event-free survival (EFS). Additional secondary objectives include characterization of the safety and tolerability of rocbrutinib relative to pirtobrutinib. Safety will be assessed through evaluation of adverse events (AEs), serious adverse events (SAEs), adverse events of special interest, deaths, physical examinations, vital signs, electrocardiograms, and clinical laboratory assessments. AEs will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. In addition, population pharmacokinetics will be evaluated to characterize exposure-response relationships.
Exploratory objectives include evaluation of patient-reported outcomes and health-related quality of life, as well as biomarker assessments aimed at characterizing disease biology, mechanisms of response and resistance, and potential predictors of clinical benefit.
2,036 studies on the registry are indexed under Leukemia, Lymphocytic, Chronic, B-Cell; 237 are open to participants now.
This study's planned enrollment of 306 is above the median of 39 across 1,603 interventional studies indexed under Leukemia, Lymphocytic, Chronic, B-Cell.
Browse Leukemia, Lymphocytic, Chronic, B-Cell studies →Newave Pharmaceutical Inc is the lead sponsor of 4 studies on the registry; 3 are open to participants now.
Compared within Leukemia, Lymphocytic, Chronic, B-Cell, this study's primary condition as ClinicalTrials.gg classifies it; the registry's first condition term is Leukemia, B-Cell. The counts are of registry records indexed under each term, refreshed daily. How we classify →
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
200mg daily
Drug: Rocbrutinib
200mg daily
Drug: Pirtobrutinib
The new generation, highly potent, ultra-selective BTK inhibitor with covalent and non-covalent dual binding mechanism, targeting both WT BTK and mutant BTK
Pirtobrutinib is a non-covalent BTK inhibitor.
PFS assessed by IRC
Progression-Free Survival assessed by independent review committee. PFS is defined as the time from the date of randomization to disease progression or death from any cause, whichever occurs first. Those who do not experience disease progression or death at the time of analysis are censored according to the last evaluation time point.
Time frame: From randomization until disease progression or death from any cause, assessed up to approximately 4 years.
OS
Overall survival is defined as the time from the date of randomization to death from any cause. Those who did not die during the analysis were censored according to the last date the subject is known to be alive.
Time frame: From randomization until death from any cause, assessed up to approximately 4 years
PFS assessed by INV
Progression free survival assessed by investigator
Time frame: From randomization until disease progression or death from any cause, assessed up to approximately 4 years.
ORR
Overall response rate
Time frame: From randomization until disease progression, assessed up to approximately 4 years
DOR
Duration of response
Time frame: From first documented response until disease progression or death, assessed up to approximately 4 years
TTNT
Time to next treatment
Time frame: From randomization to start of next anti-CLL/SLL treatment, assessed up to approximately 4 years.
EFS
Event free survival
Time frame: From randomization until an event occurs, assessed up to approximately 4 years.
Safety and tolerability
Safety and tolerability will be assessed by the incidence, severity, and relationship of adverse events (AEs) and serious adverse events (SAEs), including deaths; adverse events leading to dose modification or discontinuation; and changes in clinical laboratory parameters. Adverse events will be graded per NCI CTCAE v5.0, with specific monitoring for clinically significant cardiac arrhythmias and bleeding events.
Time frame: From first dose through 30 days after the last dose of study treatment (up to approximately 4 years)
Health related quality of Life
Health-related quality of life (HRQoL) will be assessed using validated patient-reported outcome (PRO) questionnaires to evaluate participants' functioning and symptoms over time. HRQoL endpoints will include change from baseline in overall health status and selected symptom and function domains. For the Global Health Status/QoL and functional scales, higher scores indicate better quality of life and functioning. For symptom scales/items, higher scores indicate greater symptom burden (worse symptoms).
Time frame: From baseline through end of treatment and follow-up, assessed up to approximately 4 years.
Plan to share: Undecided
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From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Rocbrutinib
Leukemia, Lymphocytic, Chronic, B-Cell →