NCT07342478

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
306

participants targeted

Target at P50-P75 for phase_3

Timeline
52mo left

Started Apr 2026

Typical duration for phase_3

Geographic Reach
1 country

3 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
Apr 2026Jul 2030

First Submitted

Initial submission to the registry

January 13, 2026

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 15, 2026

Completed
3 months until next milestone

Study Start

First participant enrolled

April 23, 2026

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2029

Expected
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 30, 2030

Last Updated

April 30, 2026

Status Verified

April 1, 2026

Enrollment Period

3.5 years

First QC Date

January 13, 2026

Last Update Submit

April 24, 2026

Conditions

Keywords

RocbrutinibLP-168PirtobrutinibJaypircaPhase 3RandomizedOpen-labelRelapsed or refractoryCLLSLLCLL/SLLChronic lymphocytic leukemiaSmall lymphocytic lymphomaCovalent BTK inhibitor pretreatedcBTKi pretreated / cBTKi-exposedBTK inhibitorNon-covalent BTK inhibitorNext-generation BTKiDual-binding BTKiFourth-generation BTKiOral once dailyProgression-free survivalPFSIndependent review committeeIRC-assessediwCLL 2018Lugano 2014del(17p)TP53 mutationPrior BCL2 inhibitor exposureeason for prior BTKi discontinuation (progression vs intolerance)Global

Outcome Measures

Primary Outcomes (1)

  • 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.

    From randomization until disease progression or death from any cause, assessed up to approximately 4 years.

Secondary Outcomes (7)

  • OS

    From randomization until death from any cause, assessed up to approximately 4 years

  • PFS assessed by INV

    From randomization until disease progression or death from any cause, assessed up to approximately 4 years.

  • ORR

    From randomization until disease progression, assessed up to approximately 4 years

  • DOR

    From first documented response until disease progression or death, assessed up to approximately 4 years

  • TTNT

    From randomization to start of next anti-CLL/SLL treatment, assessed up to approximately 4 years.

  • +2 more secondary outcomes

Other Outcomes (1)

  • Health related quality of Life

    From baseline through end of treatment and follow-up, assessed up to approximately 4 years.

Study Arms (2)

Rocbrutinib

EXPERIMENTAL

200mg daily

Drug: Rocbrutinib

Pirtobrutinib

ACTIVE COMPARATOR

200mg daily

Drug: Pirtobrutinib

Interventions

The new generation, highly potent, ultra-selective BTK inhibitor with covalent and non-covalent dual binding mechanism, targeting both WT BTK and mutant BTK

Rocbrutinib

Pirtobrutinib is a non-covalent BTK inhibitor.

Pirtobrutinib

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age ≥18 years;
  • Histologically confirmed CLL/SLL iwCLL 2018;
  • Relapsed or refractory disease requiring treatment;
  • Previously treated with prior lines of therapy including a covalent BTK inhibitor;
  • Measurable disease;
  • ECOG 0-2;
  • Adequate marrow, hepatic, and renal function;
  • TP53 mutation status confirmed by NGS;
  • p deletion status confirmed by FISH;

You may not qualify if:

  • Prior ncBTKi or BTK degraders;
  • Richter's transformation;
  • Confirmed prolymphocytic leukemia;
  • Uncontrolled comorbidities or infections;
  • Known CNS involvement by CLL/SLL;
  • Prior malignancy requiring active treatment (except certain adequately treated cancers) per protocol;
  • Pregnancy or breastfeeding;
  • Concomitant medications or conditions prohibited by protocol (e.g., strong drug-drug interaction risk);

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Optum Medical Group (Rhodes) P.C.

Las Vegas, Nevada, 89102, United States

RECRUITING

OSU Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

NOT YET RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, B-CellRecurrenceLeukemia, Lymphocytic, Chronic, B-CellChromosome 17 deletion

Interventions

pirtobrutinib

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsChronic Disease

Central Study Contacts

Anna Y Chen, M.D., Ph.D.

CONTACT

Stephen Anthony, D.O.

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 13, 2026

First Posted

January 15, 2026

Study Start

April 23, 2026

Primary Completion (Estimated)

October 30, 2029

Study Completion (Estimated)

July 30, 2030

Last Updated

April 30, 2026

Record last verified: 2026-04

Locations