Pirtobrutinib + Mosunetuzumab for Follicular Lymphoma

Overseen By Mengyang Di, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Autoimmune disease, CNS disease, Cardiovascular, 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: 1

Duration: 52 weeks

22 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how pirtobrutinib and mosunetuzumab work together to help people with follicular lymphoma that has returned or not responded to other treatments. Pirtobrutinib blocks a protein that promotes cancer cell growth, while mosunetuzumab aids T cells in attacking the cancer. Combining these treatments might enhance effectiveness and reduce certain side effects. This trial may suit those who have tried at least two other treatments for grade 1-3a follicular lymphoma without success or have experienced a recurrence. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot participate if you have used certain cancer treatments or therapies recently, such as monoclonal antibodies or chemotherapeutic agents, within a specified time before starting the trial.

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

Research is investigating the safety of combining pirtobrutinib and mosunetuzumab to treat follicular lymphoma. In other studies, mosunetuzumab demonstrated an 80% response rate, surpassing the 65% seen in real-world data, suggesting strong efficacy. However, safety remains a key concern.

Mosunetuzumab can cause cytokine release syndrome (CRS), a side effect where the immune system releases too many proteins into the blood too quickly. Combining it with pirtobrutinib might help reduce this side effect. Pirtobrutinib blocks certain proteins that aid cancer cell growth and is generally well-tolerated.

This study is in its early stages, focusing primarily on the treatment's safety for participants. While there is hope that combining these drugs may be safe, further research is needed to confirm this. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about pirtobrutinib and mosunetuzumab for follicular lymphoma because they bring innovative mechanisms to the table. Unlike most treatments that primarily focus on chemotherapy, pirtobrutinib is a highly selective BTK inhibitor that targets specific proteins involved in the growth of cancer cells, potentially leading to fewer side effects. Mosunetuzumab, on the other hand, is a bispecific antibody that redirects the body's immune system to attack the cancer cells directly. This dual approach not only targets the cancer more precisely but also harnesses the power of the immune system, offering new hope for more effective and targeted treatment.

What evidence suggests that pirtobrutinib and mosunetuzumab could be effective for follicular lymphoma?

Research has shown that mosunetuzumab yields promising results for patients with relapsed or refractory follicular lymphoma. Studies found that 80% of patients experienced a reduction in their cancer. On average, patients lived for 24 months without their cancer worsening. In this trial, participants will receive a combination of mosunetuzumab and pirtobrutinib. Pirtobrutinib blocks a protein called BTK, which aids cancer cell growth. By blocking BTK, pirtobrutinib may help stop cancer growth and enhance the effectiveness of T cell-based treatments like mosunetuzumab. Using these treatments together could improve their ability to kill cancer cells and reduce some side effects. ^{2 3 6 7 8}

Who Is on the Research Team?

Mengyang Di, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

The PROMOTE-FL trial is for patients with grades 1-3A follicular lymphoma that has either relapsed or hasn't responded to previous treatments. Participants must meet specific health criteria, which are not detailed here.

Inclusion Criteria

Aspartate aminotransferase and alanine aminotransferase ≤ 3 x the upper limit of normal (ULN)

Activated partial thromboplastin time (or partial thromboplastin time) and prothrombin (or international normalized ratio) ≤ 1.5 ULN

Estimated creatinine clearance (CL) ≥ 30 mL/min by Cockcroft-Gault formula: (140 - age) x body weight (kg) x 0.85 (if female) serum creatinine (mg/dl) x 72 or other institutional standard methods (e.g., based on nuclear medicine renal scan)

Exclusion Criteria

Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible

Patients who have tested positive for human immunodeficiency virus (HIV) are excluded due to risk of opportunistic infections with both HIV and BTK inhibitors. For patients with unknown HIV status, HIV testing will be performed at Screening and result must be negative for enrollment

Pregnant or breast-feeding women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive pirtobrutinib orally once daily starting 7 days prior to mosunetuzumab and continue for up to 52 weeks. Mosunetuzumab is administered intravenously on days 1, 8, and 15 of cycle 1, then on day 1 of remaining cycles, repeating every 21 days for up to 17 cycles.

52 weeks

Multiple visits (in-person) for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then at standard of care intervals for up to 4 years.

4 years

Regular visits (in-person) at standard of care intervals

What Are the Treatments Tested in This Trial?

Interventions

• Mosunetuzumab
• Pirtobrutinib

Trial Overview

This phase II trial tests the combination of pirtobrutinib and mosunetuzumab in treating relapsed/refractory follicular lymphoma. Pirtobrutinib blocks a protein that signals cancer cells to grow, while mosunetuzumab recruits T cells to attack the cancer.

How Is the Trial Designed?

Group I: Treatment (pirtobrutinib, mosunetuzumab) Experimental Treatment 9 Interventions

Patients receive pirtobrutinib PO QD on 7 days prior to the start of mosunetuzumab (day -7) and continue it until up to 52 weeks. Patients receive mosunetuzumab intravenously (IV) on days 1, 8, and 15 of cycle 1 then on day 1 of remaining cycles. Cycles of mosunetuzumab repeat every 21 days for up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients with a CR after cycle 8 discontinue mosunetuzumab. Patients also undergo blood sample and oral swab and/or rectal swab collection, tissue biopsy, CT, and PET/CT throughout the study. Additionally, patients may undergo bone marrow aspiration and biopsy at screening and after cycle 8.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a study of 64 HER2-positive metastatic breast cancer patients treated with pyrotinib, the objective response rate was 73.4%, indicating that pyrotinib is highly effective even for patients previously treated with lapatinib.

The most common grade 3 adverse events were manageable, with diarrhea occurring in 28.1% of patients, suggesting that pyrotinib has an acceptable safety profile for treating this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of the Efficacy and Safety of a Novel Irreversible HER2 Tyrosine Kinase Inhibitor Pyrotinib in Patients with HER2-Positive Metastatic Breast Cancer. Sun, Y., Chen, B., Li, J., et al.[2022]

In a study of 470 Japanese patients with imatinib-resistant or intolerant gastrointestinal stromal tumors, sunitinib demonstrated good efficacy with a 20% objective response rate and a median progression-free survival of 22.4 weeks.

The treatment was generally well-tolerated, with 70% of patients experiencing grade ≥ 3 adverse events, but specific early adverse events like hand-foot syndrome and leukopenia were linked to improved progression-free survival, indicating they may serve as positive prognostic markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor. Komatsu, Y., Ohki, E., Ueno, N., et al.[2022]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

Mosunetuzumab, a bispecific antibody targeting CD20 and CD3, has received conditional approval in the EU for treating adults with relapsed or refractory follicular lymphoma after at least two prior therapies.

This approval marks a significant milestone in the development of mosunetuzumab, highlighting its potential as a new treatment option for patients with difficult-to-treat lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab: First Approval. Kang, C.[2022]

In a first-in-human trial involving 230 patients with relapsed or refractory B-cell non-Hodgkin lymphomas, mosunetuzumab demonstrated a manageable safety profile with common side effects like neutropenia and cytokine release syndrome, mostly low-grade and occurring primarily in the first treatment cycle.

The treatment showed promising efficacy, with overall response rates of 34.9% for aggressive and 66.2% for indolent B-NHL, and complete response rates of 19.4% and 48.5%, respectively, indicating that mosunetuzumab can induce durable responses in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study. Budde, LE., Assouline, S., Sehn, LH., et al.[2023]

In a study comparing 90 patients from a mosunetuzumab clinical trial to 158 patients from real-world data, mosunetuzumab showed higher overall response (80% vs. 75%) and complete response rates (60% vs. 33%) in treating relapsed/refractory follicular lymphoma.

The results indicate that mosunetuzumab provides a clinically meaningful benefit as a chemotherapy-free treatment option, with better progression-free survival and overall survival outcomes compared to the real-world cohort.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative effectiveness between mosunetuzumab monotherapy clinical trial and real-world data in relapsed/refractory follicular lymphoma in third or subsequent lines of systemic therapy. McGough, SF., Shamas, N., Wang, J., et al.[2023]

HER2-positive metastatic breast cancer is more aggressive and often develops resistance to treatments compared to HER2-negative tumors, making effective management crucial.

Trastuzumab is the standard treatment for HER2-positive cases, but lapatinib has been developed as a targeted therapy that works inside the cell to disrupt harmful signaling pathways, offering a potential solution to overcome resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming treatment challenges in advanced breast cancer. Harkins, B., Geyer, CE.[2018]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

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