Rocbrutinib versus other BTK inhibitors for relapsed or refractory mantle cell lymphoma

A Randomized, Open-label, Multicenter, Phase III Clinical Study Comparing Rocbrutinib Monotherapy Versus Investigator's Choice of BTK Inhibitors in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL) (PRIME Study)

This trial tests whether rocbrutinib works better than other BTK inhibitors for people with mantle cell lymphoma that returned or didn't respond after at least one prior treatment and who have not previously received a BTK inhibitor (except for intolerance).

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 394 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Guangzhou Lupeng Pharmaceutical Company LTD. (Industry-sponsored)
• Drugs / interventions: Rocbrutinib, ibrutinib, acalabrutinib, zanubrutinib, orelabrutinib
• Locations: 2 sites (Beijing, Beijing Municipality and 1 other locations)
• Trial ID: NCT07377578 on ClinicalTrials.gov

What this trial studies

Rocbrutinib is a novel, fourth-generation BTK inhibitor with both covalent and non-covalent binding that showed promising efficacy and a favorable safety profile in earlier Phase 1 and 2 studies. This randomized, open-label Phase 3 trial assigns patients to rocbrutinib or investigator's choice of an approved BTK inhibitor (ibrutinib, acalabrutinib, zanubrutinib, or orelabrutinib). Eligible participants have relapsed or refractory mantle cell lymphoma, at least one measurable lesion, prior systemic therapy, and are BTK-inhibitor naïve except for intolerance. The study follows patients for treatment response and safety at sites in China under sponsorship from Guangzhou Lupeng Pharmaceutical.

Who should consider this trial

Good fit: Adults with mantle cell lymphoma who progressed after at least one prior systemic regimen, have measurable disease, an ECOG performance status of 0–2, adequate organ function, and have not previously received a BTK inhibitor (except for intolerance).

Not a fit: People who have already been treated with a BTK inhibitor (unless stopped due to intolerance), those with poor performance status or significant organ dysfunction, pregnant or breastfeeding women, or those unable to attend study visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, rocbrutinib could offer improved disease control or a more tolerable side-effect profile compared with existing BTK inhibitors for people with relapsed or refractory MCL.

How similar studies have performed: Approved BTK inhibitors have established benefit in MCL and early Phase 1/2 data for rocbrutinib were promising, but direct Phase 3 head-to-head comparisons with other BTK inhibitors are novel.

Eligibility criteria

Inclusion Criteria:

* Diagnosed with MCL, who have received at least one prior systemic regimen(s), and have experienced disease progression on the most recent line of therapy.
* Have at least one measurable lesion according to the Lugano Response Criteria 2014.
* Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2.
* Life expectancy ≥ 12 weeks.
* Adequate coagulation function, liver and kidney function, bone marrow hematopoietic function, etc.
* Toxicities or complications from prior anti-tumor therapy have recovered to Grade ≤1 according to NCI CTCAE v5.0.
* All male subjects and female subjects of childbearing potential must strictly use medically approved contraception throughout the entire study period. All male subjects must also avoid sperm donation during the above period. For women of childbearing potential, the result of serum pregnancy test must be obtained. Women must be non-lactating.
* Subject voluntarily enrolls and signs the informed consent form, and agrees to comply with the study treatment plan and visit schedule.

Exclusion Criteria:

* Hypersensitivity to Rocbrutinib or any study drug in the control group.
* Prior treatment with any BTK-targeted therapy (except for intolerance).
* Central nervous system (CNS) involvement by lymphoma.
* History of other malignancy (except MCL) within the past 2 years, excluding radically cured skin basal cell carcinoma, cervical carcinoma in situ, breast carcinoma in situ, localized squamous cell carcinoma, etc.
* History of major cardiovascular events within 6 months prior to randomization.
* Presence of any severe and/or uncontrolled systemic disease that, in the investigator's judgment, or have poor cardiac function.
* Uncontrolled active bacterial, fungal, or viral systemic infection, or active tuberculosis infection.
* Any medical condition that could interfere with the absorption, distribution, metabolism, or excretion (ADME) of the investigational drug or the evaluation of study outcomes.

Where this trial is running

Beijing, Beijing Municipality and 1 other locations

• Beijing Cancer hospital — Beijing, Beijing Municipality, China (Recruiting)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Yuqin Song

Conditions Mantle Cell Lymphoma; BTK inhibitor; Rocbrutinib