A Phase Ib/II Study of Rocbrutinib in Combination With Lacutoclax in Patients With B-Cell Malignancies

May 20, 2026 updated by: Guangzhou Lupeng Pharmaceutical Company LTD.

A Phase Ib/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of BTK Inhibitor Rocbrutinib in Combination With BCL-2 Inhibitor Lacutoclax in Patients With B-Cell Malignancies

BTK inhibitors and BCL-2 inhibitors have demonstrated significant clinical activity in mature B-cell malignancies, and combination therapy may provide improved clinical benefit. This is a multi-center, open-label, single-arm Phase Ib/II clinical study. The purpose of this clinical trial is to investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of Rocbrutinib, a fourth-generation Bruton tyrosine kinase inhibitor (BTKi), in combination with the BCL-2 inhibitor Lacutoclax in patients with mature B-cell malignancies. The Phase Ib will use a classic 3+3 dose-escalation design to evaluate dose-limiting toxicities (DLTs), determine the maximum tolerated dose (MTD), and identify the recommended dosing regimen. The Phase II portion is intended to further evaluate the efficacy and safety of the combination therapy.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

92

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥18 years, regardless of sex.

  2. Ib: Histologically confirmed diagnosis of CLL/SLL (per 2018 iwCLL criteria) or B-cell malignancies (per 2022 WHO classification), including: MCL, DLBCL, FL, and WM. Must have received at least one prior line of systemic therapy, with documented disease progression or intolerance.

    II: For Treatment-naïve (TN) CLL/SLL patients: Must meet iwCLL treatment indications and no prior systemic therapy. For R/R CLL/SLL patients: at least one prior systemic therapy with documented disease progression or intolerance.

  3. Have at least one measurable lesion.
  4. Phase Ib: ECOG performance status ≤1; phase II: ECOG performance status ≤2.
  5. Life expectancy ≥ 12 weeks.
  6. Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function.
  7. Male patients and female patients of childbearing potential must agree to use effective contraception during the study and for 90 days after the last dose of study treatment. Female patients of childbearing potential must have a negative pregnancy test before study treatment and must not be breastfeeding. Male patients must not donate sperm during the study and for 90 days after the last dose.
  8. Participation is voluntary, requiring signed informed consent and compliance with the treatment regimen and visit schedule.

Exclusion Criteria:

  1. Known hypersensitivity or intolerance to Rocbrutinib, Lacutoclax, or any of their excipients; prior treatment with any BCL-2 inhibitor; or prior treatment with both covalent and non-covalent BTK inhibitors.
  2. Use of systemic corticosteroids at doses equivalent to >20 mg/day of prednisone for ≥3 days within 7 days prior to the first dose.
  3. History of or currently suspected Richter's syndrome.
  4. Known or suspected central nervous system (CNS) involvement.
  5. Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT), or autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor T-cell (CAR-T) therapy within 90 days before the first dose of study treatment.
  6. Received antitumor therapy, investigational agents, major surgery, severe trauma, or live attenuated vaccines within 4 weeks or 5 half-lives prior to the first dose of study treatment.
  7. Received herbal medicines for antitumor treatment, or localized radiotherapy within 14 days prior to the first dose of study treatment.
  8. Use of moderate or strong CYP3A inhibitors within 7 days prior to the first dose of study treatment, or consumption of grapefruit, grapefruit juice, starfruit, or Seville oranges within 3 days prior to prior to the first dose.
  9. History of other active malignancies within the past 3 years, except for curatively treated basal cell carcinoma, localized squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or other malignancies considered cured.
  10. Any severe and/or uncontrolled systemic disease, or any other condition that, in the opinion of the investigator, makes the patient unsuitable for participation in the study.
  11. Any of the following events within 6 months prior to the first dose: Symptomatic arrhythmia, myocardial infarction, intracranial hemorrhage, or Stroke.
  12. Impaired cardiac function.
  13. Any uncontrolled systemic infection.
  14. Conditions that may impair oral drug administration or significantly affect absorption or pharmacokinetics of the study drug.
  15. Unable to discontinue moderate or strong CYP3A inhibitors or inducers, P-gp (P-glycoprotein) inhibitors, sensitive substrates of OATP1B3 or CYP2C8 during the study period.
  16. Received vaccination with any live-attenuated vaccines within 4 weeks prior to the first dose of study treatment.
  17. Evidence of an active bleeding constitution or a history of significant hemorrhagic disorders.
  18. Requirement for ongoing therapy with warfarin or other vitamin K antagonists.
  19. Presence of an active, uncontrolled, or symptomatic autoimmune disease that requires systemic treatment.
  20. Any other condition that, in the investigator's judgment, makes the patient unsuitable for study participation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Lacutoclax+Rocbrutinib
Drug: Lacutoclax+Rocbrutinib

Phase Ib dose-escalation study of Rocbrutinib in combination with Lacutoclax. Rocbrutinib will be administered at a fixed dose of 150 mg once daily (QD), while Lacutoclax will be dose-escalated. Initial dose levels include Lacutoclax 200 mg QD and 400 mg QD in 28-day treatment cycles.Treatment will continue until disease progression, unacceptable toxicity/intolerance, or completion of the protocol-defined treatment duration, whichever occurs first.

In phase II, participants will receive Rocbrutinib monotherapy for 8-12 weeks prior to combination treatment. Upon initiation of combination therapy, Lacutoclax will undergo dose ramp-up to the target dose and will then be administered continuously at the target dose. Treatment will continue until disease progression, unacceptable toxicity/intolerance, or completion of the protocol-defined treatment duration, whichever occurs first.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase Ib: Dose-limiting toxicity (DLT)
Time Frame: At the end of Cycle 1 (the length of cycle 1 is 28 days)
At the end of Cycle 1 (the length of cycle 1 is 28 days)
Phase Ib: Maximum Tolerated Dose (MTD)
Time Frame: At the end of Cycle 1 (the length of cycle 1 is 28 days)
At the end of Cycle 1 (the length of cycle 1 is 28 days)
Phase Ib: Adverse events as assessed by CTCAE v5.0
Time Frame: From the first administration to 28 days after the last administration
From the first administration to 28 days after the last administration
Phase Ib: Time to Maximum Plasma Concentration (Tmax)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase Ib: Maximum Plasma Concentration (Cmax)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase Ib: Area Under the Plasma Concentration-Time Curve from Time Zero to Time t (AUC0-t)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase Ib: Half-life (t1/2)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase II: Undetectable minimal residual disease (uMRD) rate assessed by flow cytometry
Time Frame: Up to approximately three years
Up to approximately three years

Secondary Outcome Measures

Outcome Measure
Time Frame
Phase II: Maximum Plasma Concentration (Cmax)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase II: Time to Maximum Plasma Concentration (Tmax)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase II: Area Under the Plasma Concentration-Time Curve from Time Zero to Time t (AUC0-t)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Phase II: Half-life (t1/2)
Time Frame: From 1 hour prior to administration to 24 hours post-dose
From 1 hour prior to administration to 24 hours post-dose
Overall Response Rate(ORR)
Time Frame: Up to approximately three years
Up to approximately three years
Progression-free Survival(PFS)
Time Frame: Up to approximately three years
Up to approximately three years
Overall Survival(OS)
Time Frame: Up to approximately three years
Up to approximately three years
Phase II: Adverse events as assessed by CTCAE v5.0
Time Frame: From the first administration to 28 days after the last administration
From the first administration to 28 days after the last administration
Complete Response Rate (CRR)
Time Frame: Up to approximately three years
Up to approximately three years
Duration of Response (DOR)
Time Frame: Up to approximately three years
Up to approximately three years
Phase Ib: Undetectable Minimal Residual Disease (uMRD) Rate assessed by flow cytometry
Time Frame: Up to approximately three years
Up to approximately three years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Guangzhou Lupeng Pharmaceutical Company LTD.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 30, 2026

Primary Completion (Estimated)

June 30, 2029

Study Completion (Estimated)

May 30, 2033

Study Registration Dates

First Submitted

May 20, 2026

First Submitted That Met QC Criteria

May 20, 2026

First Posted (Actual)

May 27, 2026

Study Record Updates

Last Update Posted (Actual)

May 27, 2026

Last Update Submitted That Met QC Criteria

May 20, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LP-10822

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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