XmAb24306 + Atezolizumab for Solid Tumors

Recruiting at 59 trial locations

Overseen By Reference Study ID Number: GO41596 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: QT prolonging drugs

Disqualifiers: Cardiovascular disease, Liver disease, Diabetes, CNS metastases, 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

195 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug, XmAb24306, alone or with another drug to help the immune system fight advanced or spreading cancers. It aims to see if this combination can better target and destroy cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does mention that participants on anticoagulants must have a stable regimen. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Atezolizumab in treating solid tumors?

Atezolizumab has shown effectiveness in treating various cancers, including bladder cancer and triple-negative breast cancer, by blocking a protein that helps cancer cells hide from the immune system. In bladder cancer, it improved response rates and survival, and in breast cancer, it helped delay disease progression when combined with another drug. ^{1 2 3 4 5}

Is the combination of XmAb24306 and Atezolizumab safe for humans?

Atezolizumab, also known as Tecentriq, has been used in various cancer treatments and generally has a favorable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious immune-related side effects like pneumonitis (lung inflammation) and hepatitis (liver inflammation) are less common. Safety data specific to the combination with XmAb24306 is not provided, but Atezolizumab alone has been considered safe in multiple trials. ^{1 2 3 4 6}

What makes the drug combination of XmAb24306 and Atezolizumab unique for treating solid tumors?

The combination of XmAb24306 and Atezolizumab is unique because it involves Atezolizumab, an immune checkpoint inhibitor that blocks PD-L1, enhancing the body's immune response against tumors. This approach is novel as it leverages the immune system to target cancer cells, which is different from traditional chemotherapy that directly attacks cancer cells. ^{1 2 3 4 7}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with advanced solid tumors who are in fairly good health (ECOG 0 or 1), have a life expectancy of at least 12 weeks, and functioning major organs. They must not be pregnant, breastfeeding, or planning to become pregnant. Participants should not have significant heart disease, uncontrolled diabetes, active infections like TB or hepatitis B/C, autoimmune diseases, HIV, or a history of other cancers within the last three years.

Inclusion Criteria

My blood and organs are functioning well.

I am fully active or can carry out light work.

My doctor expects me to live for at least 12 more weeks.

Exclusion Criteria

I have had cancer spread to the lining of my brain and spinal cord.

My Type 2 diabetes is not well-managed.

I have had a previous transplant of stem cells or an organ.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1a Dose Escalation

Participants will receive XmAb24306 until study treatment discontinuation or study termination

Variable

Phase 1a Dose Expansion

Participants will receive XmAb24306 until study treatment discontinuation or study termination

Variable

Phase 1b Dose Escalation

Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination

Variable

Phase 1b Dose Expansion

Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination

Variable

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Atezolizumab
• XmAb24306

Trial Overview The study tests XmAb24306 alone and combined with Atezolizumab in patients with advanced solid tumors. It aims to assess safety and how well the body handles these treatments (pharmacokinetics) as well as their effectiveness against tumor growth.

Participant Groups

Group I: Phase 1b Dose Expansion Experimental Treatment 2 Interventions

Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination.

Group II: Phase 1b Dose Escalation Experimental Treatment 2 Interventions

Participants will receive XmAb24306 and atezolizumab until study treatment discontinuation or study termination.

Group III: Phase 1a Dose Expansion Experimental Treatment 1 Intervention

Participants will receive XmAb24306 until study treatment discontinuation or study termination.

Group IV: Phase 1a Dose Escalation Experimental Treatment 1 Intervention

Participants will receive XmAb24306 until study treatment discontinuation or study termination.

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

Atezolizumab is a monoclonal antibody that targets PD-L1, which is being developed for treating various blood cancers and solid tumors, showing promise in cancer immunotherapy.

It has already been approved in the US as a second-line treatment for urothelial carcinoma and is pending approval for non-small cell lung cancer, highlighting its potential efficacy in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: First Global Approval. Markham, A.[2019]

Atezolizumab is an FDA-approved treatment for advanced bladder cancer that works by blocking the PD-L1/PD-1 immune checkpoint, enhancing T-cell immunity against tumors.

In clinical trials, atezolizumab showed a 15% objective response rate in patients whose cancer progressed after chemotherapy, and a 24% response rate in chemotherapy-naïve patients, with a favorable safety profile compared to other second-line treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. Inman, BA., Longo, TA., Ramalingam, S., et al.[2022]

Atezolizumab, the first anti-PD-L1 monoclonal antibody approved by the FDA, has shown promising efficacy in treating metastatic triple-negative breast cancer, supported by data from the Phase III IMpassion130 trial.

The review highlights the pharmacodynamic and pharmacokinetic properties of atezolizumab, emphasizing its safety and effectiveness in various cancers, including small-cell lung cancer and renal cell cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. Mavratzas, A., Seitz, J., Smetanay, K., et al.[2020]

Atezolizumab, combined with nab-paclitaxel, significantly improved progression-free survival in patients with advanced triple-negative breast cancer (TNBC) compared to placebo, based on the phase III IMpassion130 trial involving patients with unresectable locally advanced or metastatic TNBC.

While the combination therapy showed a tolerable safety profile, with common side effects like neutropenia and immune-related adverse events, it did not significantly affect health-related quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. Kang, C., Syed, YY.[2020]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

Atezolizumab significantly improves overall survival in patients with metastatic non-small cell lung cancer (mNSCLC), with median survival times of 13.8 months in the atezolizumab group compared to 9.6 months in the docetaxel group in the OAK trial.

The treatment has an acceptable safety profile, with common side effects including fatigue and decreased appetite, and serious immune-related adverse events occurring in a small percentage of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. Weinstock, C., Khozin, S., Suzman, D., et al.[2022]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

References

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

Atezolizumab: First Global Approval. [2019]

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

Atezolizumab: A PD-L1-Blocking Antibody for Bladder Cancer. [2022]

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

Atezolizumab for use in PD-L1-positive unresectable, locally advanced or metastatic triple-negative breast cancer. [2020]

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

Atezolizumab (in Combination with Nab-Paclitaxel): A Review in Advanced Triple-Negative Breast Cancer. [2020]

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

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. [2022]

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

U.S. Food and Drug Administration Approval Summary: Atezolizumab for Metastatic Non-Small Cell Lung Cancer. [2022]

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

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]