LP-168 + Obinutuzumab for Chronic Lymphocytic Leukemia

Overseen By UCCC Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Zulfa Omer

Must not be taking: Anticoagulants, Steroids, CYP3A4 inhibitors

Disqualifiers: Richter's transformation, Cardiovascular disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 12 months

34 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination of LP-168 (a potential new drug) and Obinutuzumab for individuals with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that hasn't responded well to previous treatments. It examines the effectiveness of these drugs, particularly for those who have undergone therapies like BCL2 inhibitors, chemotherapy, or BTK inhibitors. Suitable candidates have already tried other CLL/SLL treatments and may have specific mutations in their cancer. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications for the trial?

The trial requires a washout period (time without taking certain medications) for some treatments, like anti-cancer therapies and certain other drugs, before starting the study drug. You should discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found LP-168 to be well-tolerated, with no unexpected or severe side effects. So far, data looks promising for LP-168's safety.

Research has shown that Obinutuzumab is generally safe as well. In various studies, most side effects were mild to moderate, such as fever or chills during infusion. Serious side effects were less common but did occur.

Overall, past studies have shown both treatments to be quite safe. However, like any treatment, there are always risks. Participants in the trial will be closely monitored to manage any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LP-168 combined with Obinutuzumab for chronic lymphocytic leukemia (CLL) because this combination targets cancer cells in a novel way. LP-168 is a next-generation BCL2 inhibitor, which can help induce cancer cell death, especially in patients whose cancer has stopped responding to other BCL2 inhibitors or chemotherapy. Obinutuzumab is a monoclonal antibody that targets the CD20 protein on cancer cells, enhancing the immune system's ability to destroy them. Together, these treatments offer a fresh approach for patients who have limited options due to resistance or intolerance to existing therapies like BTK inhibitors.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

Research is examining the effectiveness of combining LP-168 and obinutuzumab for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This trial includes two separate cohorts. Cohort 1 consists of participants who have undergone one or more prior therapies for CLL/SLL, including BCL2 inhibitors, chemotherapy, and/or BTK inhibitors. Cohort 2 involves participants previously treated with a BTK inhibitor and possessing a specific BTK gatekeeper mutation. LP-168, a new drug, shows promise in targeting specific cancer cells when used with obinutuzumab. Although data is limited, early results suggest this combination might help control the disease for a longer period. Obinutuzumab is already known to help the immune system identify and attack cancer cells. This combination aims to enhance that effect, potentially leading to better outcomes for patients who haven't responded to other treatments. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

This trial is for people with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) or similar conditions who have been treated before. It's specifically for those with a T474 mutation. The full eligibility criteria are not provided, so additional factors may apply.

Inclusion Criteria

Patients must have adequate organ and marrow function as defined below: ANC ≥1,000/mcL, unless if neutropenia is due to underlying CLL bone marrow disease. Platelets ≥ 50,000/ µL unless if thrombocytopenia is due to underlying CLL bone marrow disease then platelets of ≥20,000 is acceptable. Total bilirubin ≤1.5 x ULN (excepting Gilbert's syndrome, who may have a bilirubin > 1.5 × ULN, per discussion between the Investigator and the UC PI). AST and ALT ≤2.5 × ULN. Estimated glomerular filtration rate (by Modification of Diet in Renal Disease [MDRD] or Chronic Kidney Disease Epidemiology [CKD-EPI]) ≥ 30 mL/min.

I have CLL/SLL and have been treated with specific therapies or have a specific mutation.

I can take care of myself but might not be able to do heavy physical work.

Exclusion Criteria

My condition has progressed to Richter's transformation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive LP-168 200 mg daily for 12 cycles, with obinutuzumab starting from cycle 7

12 months

Multiple visits per cycle

Response Evaluation

Response evaluation including labs, CT scan, and bone marrow biopsy after cycle 6

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up every 6 months

6 years

Biannual visits

What Are the Treatments Tested in This Trial?

Interventions

• LP-168
• Obinutuzumab

Trial Overview The study tests LP-168 and Obinutuzumab in two separate groups of patients to see how well they work against CLL/SLL variants that have been previously treated, including those with the T474 mutation.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 2 Interventions

Cohort 2: Treatment with a prior BTKi (covalent and noncovalent) and have a BTK gatekeeper mutation in the T474 coordinate. prior treatment with BCL2 or chemotherapy will not exclude patients

Group II: Cohort 1 Experimental Treatment 2 Interventions

Cohort 1: One or more prior therapies for CLL/SLL including BCL2 inhibitor (BCL2i), and/or chemotherapy and/or BTK inhibitor (BTKi). • Note: Patients can be eligible if their CLL/SLL has been non-responsive to a covalent and noncovalent BTKi. Patients intolerant to BTKi whose disease becomes resistant to a second one are eligible to enroll. Prior treatment with CD20 will not be exclusionary.

Who Is Running the Clinical Trial?

Zulfa Omer

Lead Sponsor

Newave Pharmaceutical Inc

Industry Sponsor

Trials

4

Recruited

270+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06978088

Study Details | NCT06978088 | LP-168 and Obinutuzumab ... The goal is to establish a safe dosing regimen for the combination and to acquire pilot data characterizing the effectiveness of the combination in increasing ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S000649712500864X

Doubling down: the new deal in the clinical management of ... There are also limited data on outcomes of cBTKi after venetoclax, particularly following frontline venetoclax in combination with obinutuzumab; ...

3. ctsearchsupport.org ctsearchsupport.org/clinical-trials/lp-168-and-obinutuzumab-for-chronic-lymphocytic-leukemia-small-lymphocytic-lymphoma-cll-sll-and-variants-of-this

A drug, LP-168, in combination with obinutuzumab , to treat ... To find out if the combination of LP-168 and obinutuzumab is safe and works well to treat CLL or SLL.

4. ashpublications.org ashpublications.org/blood/article/146/7/779/537595/Hitting-the-therapeutic-bull-s-eye-with-targeted

Hitting the therapeutic bull's-eye with targeted therapy for ... Although they both are highly effective at long-term disease control, they are not currently confirmed curative, and many patients are expected to develop ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11117011/

BTK inhibitors in CLL: second-generation drugs and beyond The ongoing AMPLIFY study (NCT03836261) compares combination therapy with acalabrutinib + venetoclax ± obinutuzumab with FCR in fit patients. Zanubrutinib. The ...

6. cllsociety.org cllsociety.org/2024/06/safety-of-dual-covalent-and-noncovalent-btk-inhibitor-for-cll/

Safety of Dual Covalent and Noncovalent BTK Inhibitor for ... LP-168 is a new dual covalent and noncovalent BTK inhibitor well-tolerated in a phase 1 clinical trial. This could potentially be an option for patients who ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4622/529902/LP-168-Rocbrutinib-a-Novel-Covalent-and-Non

LP-168 (Rocbrutinib), a Novel Covalent ... - ASH Publications Updated enrollment numbers, median follow-up, responses and safety data are provided for the current ongoing Phase 1a study, which includes the GM cohort.

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123049327

Initial Results of a Phase 1 Dose Escalation Study of LP- ... LP-168 is a selective next generation inhibitor of BTK that can bind wild-type and C481-mutated BTK covalently and non-covalently, respectively, with ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06978088?term=obinutuzumab%20%20CLL&viewType=Table&rank=1

Study Details | NCT06978088 | LP-168 and Obinutuzumab ... Patients will be monitored for regular safety outside the combination using the toxicity monitoring Table 8, given we already have data confirming the safety of ...

10. 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/ ...