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

No longer recruiting at 62 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for individuals with Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia that has recurred or not responded to other treatments. The study examines the effectiveness of BTCT4465A (Mosunetuzumab) alone and in combination with atezolizumab (Tecentriq). Participants will receive varying doses to determine the optimal amount that is both safe and effective. Eligible participants have B-cell blood cancers with a specific marker (CD20) and have not succeeded with other treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that both atezolizumab and BTCT4465A (mosunetuzumab) have undergone safety testing in earlier studies. Atezolizumab, an FDA-approved immunotherapy for other uses, has a well-understood safety profile. Most people tolerate it well, though some have experienced side effects like tiredness and loss of appetite.

For mosunetuzumab, early studies in individuals with non-Hodgkin's lymphoma indicate it is generally well-tolerated. Some participants reported mild to moderate side effects, such as fever and diarrhea. The combination of these two treatments has been studied, with early research focusing on different dose levels to ensure safety.

As this is a Phase 1/2 trial, the research process is still in its early stages. More data is needed to fully understand the safety of using these treatments together. However, testing this combination in humans suggests some confidence in its safety. Always consult a doctor if there are concerns or a need for more information before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of atezolizumab and BTCT4465A (Mosunetuzumab) for treating Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia because it represents a novel approach. Unlike traditional chemotherapy and radiation, which are the current standard treatments, this combination targets the immune system to fight cancer. Atezolizumab is an immunotherapy drug that blocks the PD-L1 protein, helping immune cells attack cancer more effectively. Meanwhile, Mosunetuzumab is a bispecific antibody that directly engages T-cells to target and kill cancer cells. This dual mechanism aims to enhance the body's natural defenses and offers a promising new way to tackle these types of cancers.

What evidence suggests that this trial's treatments could be effective for Non-Hodgkin's Lymphoma and Chronic Lymphocytic Leukemia?

Research has shown that atezolizumab, a treatment in this trial, produces promising results in treating certain types of lymphoma when combined with other treatments. In some studies, it helped up to 79% of patients with follicular lymphoma by shrinking or eliminating their cancer.

Mosunetuzumab, another treatment option in this trial, also shows positive results. It has benefited patients with relapsed or hard-to-treat lymphoma, with some experiencing improvements for several months. Together, these treatments aim to help the immune system fight cancer cells, offering hope for those with challenging lymphoma cases. ^{4 6 7 8 9}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11694104/

Atezolizumab combined with immunogenic salvage ... The overall and complete response rates were 59% and 33%, respectively. The overall and complete response rates in transformed FL were 79% and 43%, respectively ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02500407

Study Details | NCT02500407 | A Safety, Efficacy and ... This is a Phase 1/2 dose-escalation study of BTCT4465A (Mosunetuzumab) administered as a single agent and in combination with atezolizumab in participants ...

3. ajmc.com ajmc.com/view/atezolizumab-immunogenic-chemotherapy-combination-shows-promise-for-dlbcl-treatment

Atezolizumab, Immunogenic Chemotherapy Combination ... For patients with FL (n = 14), complete and overall response rates registered at 43% and 79%. These rates were 23% and 38% in patients with non ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-mosunetuzumab-and-atezolizumab-for-patients-with-relapsed-or-refractory-non-hodgkins-lymphoma-and-chronic-lymphocytic-leukemia/

Study on the Safety and Effectiveness of Mosunetuzumab ... Atezolizumab is known to help the immune system attack cancer cells, and the trial is assessing whether this combination can improve treatment ...

5. ashpublications.org ashpublications.org/bloodadvances/article/9/14/3530/536801/Atezolizumab-consolidation-in-patients-with-high

Atezolizumab consolidation in patients with high-risk diffuse ... Atezolizumab consolidation in high-risk patients with DLBCL raised 2-year DFS to 87.9% and OS to 96.3%, surpassing historical outcomes.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02500407

Study Details | NCT02500407 | A Safety, Efficacy and ... A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) as a Single Agent and Combined With Atezolizumab in Non-Hodgkin's Lymphoma (NHL) and ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02500407?intr=Mosunetuzumab&aggFilters=phase:2%203%204,status:rec%20enr%20act,studyType:int&rank=10

A Safety, Efficacy and Pharmacokinetic Study of ... Also called a data safety and monitoring board, or DSMB. Early Phase 1 (formerly listed as Phase 0). A phase of research used to describe exploratory trials ...

8. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/leukemia/a-safety-and-pharmacokinetic-study-of-btct4465a--mosunetuzumab--.html

Clinical trial - Non-Hodgkin Lymphoma and Chronic Lymphoc... A clinical trial to look at how safe different doses of mosunetuzumab are to give with or without atezolizumab in people with. B‑cell non-Hodgkin's lymphoma

9. euclinicaltrials.eu euclinicaltrials.eu/ctis-public/view/2023-506820-10-00

Clinical Trials in the European Union - EMA A Safety, Efficacy and Pharmacokinetic Study of BTCT4465A (Mosunetuzumab) ... Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL). EUCT ...