Atezolizumab + BTCT4465A (Mosunetuzumab) for Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia

Recruiting at 56 trial locations

Overseen By Reference Study ID Number: GO29781 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genentech, Inc.

Must not be taking: Monoclonal antibodies, Chemotherapy

Disqualifiers: Pregnancy, Autoimmune, CNS disease, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

713 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Mosunetuzumab, both alone and with another drug called atezolizumab, in patients with blood cancers that have not responded to other treatments. These drugs work by helping the immune system find and destroy cancer cells. Atezolizumab is a medication that has been approved for use in various cancers, including breast cancer, and has shown effectiveness when combined with other treatments.

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

The trial requires that you stop taking certain medications, such as monoclonal antibodies, chemotherapy, or other investigational anti-cancer agents, at least 4 weeks before starting the study drug. You also need to stop systemic immunosuppressive medications 2 weeks before the study drug.

What data supports the effectiveness of the drug Atezolizumab + BTCT4465A (Mosunetuzumab) for Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia?

Mosunetuzumab, a component of the treatment, has shown promising results in patients with relapsed or refractory follicular lymphoma, achieving an overall response rate of 80% and a complete response rate of 60% in a phase 2 trial. ^{1 2 3 4 5}

Is the combination of Atezolizumab and Mosunetuzumab safe for humans?

Mosunetuzumab, one of the drugs in the combination, has been shown to be well tolerated in patients with relapsed or refractory B-cell lymphoma, indicating it is generally safe in humans. ^{1 5 6 7 8}

What makes the drug Atezolizumab + BTCT4465A (Mosunetuzumab) unique for treating Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia?

This drug combination is unique because it includes mosunetuzumab, a bispecific antibody that engages T-cells to target and destroy cancerous B-cells, offering a novel approach compared to traditional therapies. Mosunetuzumab has shown high efficacy in relapsed or refractory follicular lymphoma, with an 80% overall response rate, making it a promising option for patients who have not responded to other treatments. ^{1 3 4 5 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with B-cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia who have tried at least one treatment that didn't work. They should be in fairly good health otherwise, not pregnant, and haven't had certain treatments like stem cell transplants recently.

Inclusion Criteria

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

My B-cell cancer has not improved after at least one treatment and no other treatments are likely to help.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I haven't taken any immunosuppressive drugs in the last 2 weeks.

I have had a stem cell transplant using my own cells within the last 100 days or any transplant from a donor.

I haven't had radiotherapy in the last 2 weeks before starting Mosunetuzumab.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive BTCT4465A (Mosunetuzumab) via IV or SC as a single-agent or in combination with atezolizumab. Dose escalation guided by DLTs.

Variable duration based on dose escalation

Dose Expansion

Participants receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab in indication-specific cohorts.

Variable duration based on cohort

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 4 years

Treatment Details

Interventions

• Atezolizumab
• BTCT4465A (Mosunetuzumab)

Trial Overview Researchers are testing Mosunetuzumab, given by injection or IV, alone and combined with Atezolizumab to see how safe and effective they are against these blood cancers. The study has two parts: finding the right dose and then seeing how well it works in specific groups.

Participant Groups

Group I: Dose Expansion Experimental Treatment 3 Interventions

Participants will receive BTCT4465A (Mosunetuzumab) as a single-agent or in combination with atezolizumab.

Group II: Dose Escalation Experimental Treatment 3 Interventions

Participants will receive BTCT4465A (Mosunetuzumab) via intravenous (IV) infusion or subcutaneous (SC) injection as a single-agent or in combination with atezolizumab. Dose escalation will be guided by the observed incidence of DLTs at each dose level.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

In a phase 1 study involving 183 patients with relapsed or refractory B-cell non-Hodgkin lymphoma, loncastuximab tesirine demonstrated a promising overall response rate of 45.6%, with 26.7% achieving complete responses, indicating its potential as an effective treatment option.

The study established a recommended dose of 150 µg/kg for phase 2 trials, with an acceptable safety profile characterized by manageable hematologic toxicities, suggesting that loncastuximab tesirine could be a viable alternative to current therapies for this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Hamadani, M., Radford, J., Carlo-Stella, C., et al.[2022]

Mosunetuzumab, the first bispecific antibody approved for lymphoma, shows significant efficacy in treating relapsed or refractory follicular lymphoma, with an overall response rate of 80% and a complete response rate of 60%.

The approval of mosunetuzumab was based on a phase 2 trial involving patients who had undergone at least two prior lines of systemic therapy, highlighting its potential as a new treatment option for challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. Cao, Y., Marcucci, EC., Budde, LE.[2023]

Loncastuximab tesirine is an antibody-drug conjugate that targets B cell lymphomas, specifically approved for relapsed/refractory diffuse large B cell lymphoma (DLBCL) after two or more lines of treatment.

The drug works by using an anti-CD19 antibody to deliver a DNA-alkylating agent directly to B cells, enhancing its efficacy in targeting cancer cells while minimizing damage to healthy cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. Lee, A.[2021]

In a phase 2 study involving 90 patients with relapsed or refractory follicular lymphoma, mosunetuzumab achieved a complete response rate of 60%, significantly higher than the historical control rate of 14% with copanlisib, demonstrating its efficacy in this patient population.

The treatment was well tolerated, with the most common side effect being cytokine release syndrome, primarily mild to moderate in severity, and no treatment-related fatalities, indicating a favorable safety profile for outpatient administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. Budde, LE., Sehn, LH., Matasar, M., et al.[2022]

Alemtuzumab has proven effective in treating chronic lymphocytic leukemia, both as a standalone treatment and in combination with other therapies like fludarabine or rituximab, showing improved response rates and survival compared to traditional chemotherapy.

Despite its efficacy, there are safety concerns due to known toxicities associated with alemtuzumab, particularly when used in combination therapies, which require careful management to avoid adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alemtuzumab: what is the secret to safe therapy? Elter, T., Hallek, M., Montillo, M.[2017]

In a study involving 80 patients from the LOTIS-2 trial, loncastuximab tesirine (Lonca) demonstrated a significantly higher overall response rate (53.4%) compared to chemoimmunotherapy (CIT) treatments (40.3%) for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).

Lonca also showed improved overall survival, with a median survival of 10.8 months compared to 6.4 months for CIT, indicating it may be a more effective treatment option for patients with R/R DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. Hamadani, M., Chen, L., Song, Y., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Current Immunotherapeutic Approaches in T Cell Non-Hodgkin Lymphomas. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Mosunetuzumab and lymphoma: latest updates from 2022 ASH annual meeting. [2023]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Loncastuximab Tesirine: First Approval. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Alemtuzumab: what is the secret to safe therapy? [2017]

7. England pubmed.ncbi.nlm.nih.gov

Tislelizumab augment the efficacy of CD19/22 dual-targeted chimeric antigen receptor T cell in advanced stage relapsed or refractory B-cell non-Hodgkin lymphoma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Dose-intensified chemotherapy alone or in combination with mogamulizumab in newly diagnosed aggressive adult T-cell leukaemia-lymphoma: a randomized phase II study. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Matching-adjusted Indirect Comparison of the Efficacy of Loncastuximab Tesirine Versus Treatment in the Chemoimmunotherapy Era for Relapsed/Refractory Diffuse Large B-cell Lymphoma. [2022]