XmAb24306 + Atezolizumab for Solid Tumors

Not currently recruiting at 66 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, XmAb24306, alone or with atezolizumab (also known as Tecentriq), to determine their safety and effectiveness for individuals with serious solid tumors, such as those in the lungs or liver. The goal is to understand how these treatments work together against advanced cancers that have spread or cannot be cured with standard methods. Individuals with solid tumors that cannot be surgically removed or have spread may be suitable candidates for the trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that Atezolizumab, one of the treatments in this trial, has been safe in many studies, and most people tolerate it well. However, no specific safety information exists from past studies about using XmAb24306 and Atezolizumab together. This is a Phase 1 trial, marking the first time this combination is tested in humans. The main goal is to assess safety and determine the correct dose. Participants should know that this phase aims to identify any side effects and understand how the body processes the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about XmAb24306 and atezolizumab for solid tumors because of their unique approach to cancer treatment. Unlike standard therapies that primarily focus on killing cancer cells directly, XmAb24306 is designed to activate and enhance the body's immune response against cancer cells. It works as a bispecific antibody that can bind to two different targets, potentially boosting the effectiveness of the immune system. By combining this with atezolizumab, an immune checkpoint inhibitor that helps sustain the immune attack on cancer cells, this treatment aims to offer a more powerful and targeted option for patients with solid tumors. This dual action could lead to better outcomes by not only attacking the cancer more effectively but also by minimizing damage to healthy cells.

What evidence suggests that this trial's treatments could be effective for solid tumors?

Studies have shown that atezolizumab effectively treats several types of cancer, such as bladder cancer and triple-negative breast cancer. It blocks a protein that helps tumors evade the immune system, enabling the body to attack cancer cells more effectively. Research indicates that XmAb24306 enhances the ability of certain immune cells, like T-cells and natural killer cells, to attack and kill cancer cells. This trial includes separate treatment arms where participants receive XmAb24306 alone or with atezolizumab. Together, XmAb24306 and atezolizumab might offer a stronger attack on tumors by boosting immune activity. Early evidence suggests that this combination could be a promising approach for treating solid tumors. ^{6 7 8 9 10}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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, 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 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]

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 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 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, 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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0928098723000805

Complex PK-PD of an engineered IL-15/IL-15Rα–Fc fusion ... The objectives of this work are to (1) characterize the systemic PK-PD of XmAb24306 following single and repeat IV dosing in cynomolgus monkeys ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38739434/

IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates ... XmAb24306 enhances T-cell expansion, increasing T-cell proliferation and tumor cell killing, which is the main mechanism of the observed ...

3. researchgate.net researchgate.net/publication/380548969_IL-15IL-15Ra-Fc_fusion_protein_XmAb24306_potentiates_activity_of_CD3_bispecific_antibodies_through_enhancing_T_cell_expansion/download

IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates ... In vitro combination of XmAb24306 with cevostamab or anti-HER2/CD3 TDB resulted in significant enhancement of tumor cell killing, which was ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10954783/

Efbalropendekin Alfa enhances human natural killer cell ... Our results show that XmAb24306 enhances the capacity of primary human NK cells to rapidly and more efficiently kill various tumor cell lines ...

5. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/solid-tumor

UCSF Solid Tumor Clinical Trials — San Francisco Bay Area This phase I trial tests the safety and effectiveness of 18F-TRX in detecting tumors (cancer) patients with solid tumors. 18F-TRX is an imaging ...

6. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/solid-tumors/an-open-label-dose-escalation-study-to-evaluate-xmab243-88679.html

Clinical Trial – Solid Tumors – Safety and Pharmacokineti... This study will evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 alone or in combination with a checkpoint inhibitor treatment in ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04250155

NCT04250155 | An Open-Label Dose-Escalation Study to ... This study will evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 ... solid tumors. Official Title. A Phase Ia/Ib, Open-Label, ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04250155/

Clinical Trial: NCT04250155 This study will evaluate the safety, tolerability, pharmacokinetics, and activity of XmAb24306 alone or in combination with a checkpoint inhibitor treatment.

9. withpower.com withpower.com/trial/phase-1-neoplasms-2-2020-27998

XmAb24306 + Atezolizumab for Solid Tumors Safety data specific to the combination with XmAb24306 is not provided, but Atezolizumab alone has been considered safe in multiple trials. Show ...

10. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT075/761655/Abstract-CT075-Phase-1a-1b-dose-escalation-study

Phase 1a/1b dose-escalation study of efbalropendekin alfa ... This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), PD, and activity of EBA ± atezolizumab (ATZ) in Phase 1a ( ...