LP-168 for Lymphoma

Recruiting at 3 trial locations

Overseen By Anna Chen, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Newave Pharmaceutical Inc

Must not be taking: Steroids, CYP3A4 inducers

Disqualifiers: Immediate cytoreduction, ECG abnormalities, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called LP-168, tested for safety and effectiveness in people with certain B-cell blood cancers that have returned or resisted previous treatments. LP-168 is a small molecule inhibitor designed to block specific proteins that may aid cancer cell growth. Participants will take varying doses of LP-168 to determine the optimal dosage and understand how the body processes the drug. Individuals with B-cell malignancies like lymphoma or chronic lymphocytic leukemia, who have tried at least two treatments, might be suitable for this study. As a Phase 1 trial, this research aims to understand how LP-168 works in people, offering participants the chance to be among the first to receive this new treatment.

Do I need to stop my current medications to join the trial?

Yes, you may need to stop certain medications before joining the trial. You must stop any anti-cancer therapy, investigational therapy, and certain medications like strong CYP3A4 inhibitors and proton pump inhibitors at least 7 days before the trial. There is a 2-day washout period for CLL subjects coming off BCR antagonists.

Is there any evidence suggesting that LP-168 is likely to be safe for humans?

Research has shown that LP-168, also known as Rocbrutinib, was tested for safety in earlier studies. In patients with a type of lymphoma who had already tried other treatments, Rocbrutinib proved safe, as most people did not experience serious side effects.

The treatment was generally easy for people to take without many problems. This finding is important because it suggests that LP-168 might be safe for more people, even those who haven't responded to other treatments.

Since this study is in an early phase, the main goal is to learn how safe the treatment is for humans. It provides an opportunity to gather more detailed information about any side effects and how people react to different doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma?

Researchers are excited about LP-168 for lymphoma because it potentially offers a new approach compared to current treatments like chemotherapy and immunotherapy. Unlike these standard treatments, which often have extensive side effects and varying effectiveness, LP-168 is an oral medication being studied for its ability to target cancer cells with precision. This targeted action might not only enhance efficacy but also improve the safety and tolerability profile, making it a promising option for patients with lymphoma.

What evidence suggests that LP-168 might be an effective treatment for lymphoma?

Research has shown that LP-168, also known as Rocbrutinib, may help treat certain types of lymphoma. Studies have found it effective for patients whose B-cell cancers have returned or are not responding to other treatments. For instance, some trials reported high rates of complete response in patients with mantle cell lymphoma, meaning their cancer was not detectable after treatment. In this trial, participants will receive LP-168 in either a Dose Escalation Phase or a Dose Expansion Phase to further explore its safety and efficacy. LP-168 works by blocking a protein that helps cancer cells grow, making it effective even when other treatments fail due to certain mutations. Overall, early results suggest LP-168 could be a strong option for those with hard-to-treat lymphomas. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with certain B-cell malignancies who've had at least two prior treatments. They should have good kidney, liver, and bone marrow function and not be on strong immune system suppressants or certain other drugs. People with recent cancer therapies, significant heart ECG abnormalities, or a history of Richter's transformation can't join.

Inclusion Criteria

My lymphoma is a low-grade B-cell type, such as follicular or marginal zone.

My blood clotting, kidney, and liver functions are within normal ranges.

My blood counts meet the required levels for the study.

Exclusion Criteria

I haven't had any cancer except for skin cancer or treated cervical cancer in the last 3 years.

Your blood tests show high levels of amylase or lipase.

I can adjust my acid-reducing medication schedule for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive sequentially higher oral doses of LP-168 on a once or twice daily schedule for 28 days to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D)

28 days

Multiple visits for dose escalation and monitoring

Dose Expansion

Additional subjects are recruited to further explore the safety, tolerability, pharmacokinetics, and efficacy in specific subject subgroups

Up to 24 months

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LP-168

Trial Overview The study tests LP-168, an oral drug for relapsed/refractory B-cell malignancies. It's a phase I trial to see how safe it is and how the body handles it (pharmacokinetics) at different doses.

How Is the Trial Designed?

Group I: Dose Expansion Phase Experimental Treatment 1 Intervention

Additional subjects will be recruited to further explore the safety, tolerability, PK, and efficacy in specific subject subgroups.

Group II: Dose Escalation Phase Experimental Treatment 1 Intervention

Three to six subjects per treatment cohort will be assigned to receive sequentially higher oral doses of LP-168 on a once or twice daily schedule for 28 days, starting at a dose of 100 mg/day.

Who Is Running the Clinical Trial?

Newave Pharmaceutical Inc

Lead Sponsor

Trials

4

Recruited

270+

Published Research Related to This Trial

Copanlisib is effective in treating relapsed/refractory B-cell non-Hodgkin lymphoma (B-NHL), with an overall response rate of 57% and a complete response rate of 13% based on a meta-analysis of 652 patients across 8 studies.

Combination therapy with copanlisib and rituximab showed significantly higher efficacy compared to copanlisib alone, with complete response rates of 34% versus 6%, while treatment-related adverse events were manageable, with common side effects including hyperglycemia and hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of copanlisib in relapsed/refractory B-cell non-Hodgkin lymphoma: A meta-analysis of prospective clinical trials. Wang, J., Zhou, H., Mu, M., et al.[2022]

The phase III CHRONOS-3 trial demonstrated that adding copanlisib, a pan-PI3K inhibitor, to standard rituximab significantly benefits patients with relapsed indolent non-Hodgkin lymphoma.

This combination therapy was found to be safe and reduced the risk of disease progression or death by nearly 50% compared to the placebo plus rituximab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

NHL Progression Risk Cut with Copanlisib-Rituximab Combo. [2021]

PI3K inhibitors like idelalisib and duvelisib have shown effectiveness in treating chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), even in high-risk patients, with a comparable safety profile that includes autoimmune side effects.

Newer agents like copanlisib and umbralisib may offer different safety profiles, but all PI3K inhibitors can cause immune-related toxicities, highlighting the need for careful monitoring and management of side effects in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of phosphoinotiside-3 kinase inhibitors in blood cancers. Shouse, G., Danilova, OV., Danilov, AV.[2023]

ON 01910.Na (Rigosertib) effectively induces apoptosis in CLL B cells from 34 patients without harming normal T cells or B cells, suggesting a targeted approach to treatment.

The drug works through two main mechanisms: inhibiting the PI3K/AKT pathway and inducing oxidative stress, which leads to increased levels of the pro-apoptotic protein NOXA, making it a promising candidate for clinical trials in CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ON 01910.Na is selectively cytotoxic for chronic lymphocytic leukemia cells through a dual mechanism of action involving PI3K/AKT inhibition and induction of oxidative stress. Chapman, CM., Sun, X., Roschewski, M., et al.[2021]

In a phase 1 study involving 16 patients with relapsed/refractory lymphoma, SAR245409 (voxtalisib) demonstrated preliminary efficacy with one complete response and two partial responses, indicating its potential effectiveness in treating this type of cancer.

The treatment was generally well-tolerated, with common side effects including nausea (31.3%) and diarrhea (25.0%), and showed significant inhibition of key cancer pathways, suggesting a mechanism of action that could be beneficial for further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, pharmacokinetics and pharmacodynamics of SAR245409 (voxtalisib, XL765), an orally administered phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor: a phase 1 expansion cohort in patients with relapsed or refractory lymphoma. Papadopoulos, KP., Egile, C., Ruiz-Soto, R., et al.[2021]

Pilaralisib, a pan-PI3K inhibitor, was found to have an acceptable safety profile in a study of 25 patients with chronic lymphocytic leukemia (CLL) and lymphoma, with common side effects including diarrhea (92%) and pyrexia (52%).

The treatment showed preliminary efficacy, with 50% of CLL patients achieving a partial response and 60% experiencing significant nodal shrinkage, indicating potential for further development in these cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I Trial of the Pan-PI3K Inhibitor Pilaralisib (SAR245408/XL147) in Patients with Chronic Lymphocytic Leukemia (CLL) or Relapsed/Refractory Lymphoma. Brown, JR., Davids, MS., Rodon, J., et al.[2021]

Duvelisib, a dual inhibitor of PI3Kδ and PI3Kγ, has been approved by the FDA for treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma after at least two prior therapies.

The drug also received accelerated approval for patients with relapsed or refractory follicular lymphoma, indicating its potential effectiveness in these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib Approved for Leukemia, Lymphoma. [2019]

In a phase 2 trial involving 167 patients with relapsed or refractory lymphoma or chronic lymphocytic leukaemia, voxtalisib demonstrated an overall response rate of 18.3%, with the highest efficacy observed in patients with follicular lymphoma (41.3%).

Voxtalisib was found to have an acceptable safety profile, with common side effects including diarrhea, fatigue, and nausea, while serious adverse events occurred in 58.1% of patients, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxtalisib (XL765) in patients with relapsed or refractory non-Hodgkin lymphoma or chronic lymphocytic leukaemia: an open-label, phase 2 trial. Brown, JR., Hamadani, M., Hayslip, J., et al.[2020]

Duvelisib, an oral dual PI3K-delta/gamma inhibitor, has shown superior progression-free survival in patients with chronic lymphocytic leukemia (CLL) compared to the standard treatment of ofatumumab, highlighting its efficacy as a new treatment option.

Despite its high efficacy, duvelisib is associated with significant adverse events that may lead to treatment interruptions, necessitating careful management strategies such as dose adjustments and supportive care to enhance patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib for the treatment of chronic lymphocytic leukemia. Frustaci, AM., Tedeschi, A., Deodato, M., et al.[2022]

Duvelisib is an effective oral treatment for relapsed chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), targeting the B-cell receptor pathway through inhibition of phosphoinositide-3 kinase.

Current research is focused on optimizing duvelisib's use by exploring fixed-duration combinations and alternative dosing schedules to minimize immune-related side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib for CLL/SLL and follicular non-Hodgkin lymphoma. Patel, K., Danilov, AV., Pagel, JM.[2022]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3119/533654/Rocbrutinib-a-New-Generation-BTK-Inhibitor

Rocbrutinib, a New-Generation BTK Inhibitor, Demonstrates ... Rocbrutinib, a New-Generation BTK Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Non-GCB Diffuse Large B Cell Lymphoma ...

2. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper205775.html

Paper: LP-168 (Rocbrutinib), a Novel Covalent and Non- ... Below we describe initial safety and efficacy results of a R/R CLL gatekeeper mutation cohort of rocbrutinib and overall study updates.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123096350

Safety and Efficacy Results from the Phase I Study of ... In this Phase 1 trial, the novel BTK inhibitor LP-168 demonstrated a high CR rate and durable response in heavily pre-treated R/R MCL including blastoid/ ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05716087

NCT05716087 | A Study of Rocbrutinib in Participants with ... This is an open-label, single arm, multi-center Phase 2 study of oral Rocbrutinib in patients with mantle cell lymphoma who are failed or relapsed after ...

5. cllsociety.org cllsociety.org/2025/06/rocbrutinib-a-dual-covalent-and-non-covalent-btk-inhibitor/

Rocbrutinib - a Dual Covalent and Non-Covalent BTK ... Rocbrutinib (formerly LP-168) is a next-generation BTKi that works both covalently and noncovalently. It is capable of binding wild-type BTK, BTK with C481 ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124058713

Rocbrutinib, a New-Generation BTK Inhibitor ... Rocbrutinib has demonstrated a high CR and response rate in heavily pre-treated R/R non-GCB DLBCL with favorable safety profiles.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7098

An open label, single arm, multicenter phase II study of the ... An open-label, multicenter, single-arm, phase II study to assess the efficacy, safety, tolerability, and pharmacokinetics of LP-168 in Chinese patients with R/ ...