Cabozantinib + Atezolizumab for Lung Cancer

(Cabatezo-1 Trial)

Recruiting at 3 trial locations

Overseen By Margana Whyte

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jun Zhang, MD, PhD

Must not be taking: Anticoagulants, Vaccines, Immunostimulatory agents

Disqualifiers: Psychiatric illness, Active infection, Autoimmune disease, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 12 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

NSCLC patients with low expression level of PD-L1, esp. those with its level less than 1%, do not derive much benefit from anti-PD-1/L1 therapy (e.g. atezoilzumab). In this study, investigators hypothesize that the combination of cabozantinib (a multi-kinase inhibitor) and atezolizumab will result in better therapeutic value.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like investigational therapies, some anticoagulants, and specific cancer treatments must be stopped before joining the study. It's best to discuss your current medications with the study team to see if any changes are needed.

What data supports the effectiveness of the drug Atezolizumab for lung cancer?

Atezolizumab has shown effectiveness in treating advanced non-small cell lung cancer (NSCLC) by significantly prolonging overall survival compared to traditional chemotherapy, as demonstrated in clinical trials. It works by blocking certain proteins that help cancer cells evade the immune system, making it a valuable option for patients whose cancer has progressed after chemotherapy. ^{1 2 3 4 5}

Is the combination of Cabozantinib and Atezolizumab safe for humans?

Atezolizumab (also known as Tecentriq) has been studied in various cancers, including lung and bladder cancer, and is generally considered to have an acceptable safety profile. Common side effects include fatigue, decreased appetite, and nausea, while more serious effects can include lung inflammation and liver issues. Cabozantinib (also known as Cabometyx) is not specifically mentioned in the provided research, so its safety profile in combination with Atezolizumab is not detailed here. ^{1 2 3 6 7}

What makes the drug combination of Cabozantinib and Atezolizumab unique for lung cancer treatment?

The combination of Cabozantinib and Atezolizumab is unique because it combines a targeted therapy (Cabozantinib) with an immune checkpoint inhibitor (Atezolizumab), potentially enhancing the immune system's ability to fight lung cancer by blocking specific proteins that help cancer cells evade immune detection. ^{1 2 3 5 8}

Research Team

Jun Zhang, MD, PhD

Principal Investigator

University of Kansas Medical Center

Eligibility Criteria

Adults with advanced/metastatic non-small cell lung cancer (NSCLC) and low PD-L1 expression (<1%) who haven't benefited from anti-PD-1/L1 therapy. They must have recovered from previous treatments, not be pregnant or breastfeeding, use contraception, and have no other cancers that could affect the trial. HIV-positive patients can join if stable on antiretroviral therapy.

Inclusion Criteria

My advanced lung cancer has low PD-L1 levels, confirmed by a specific test.

You have at least one specific area of the body that can be measured and evaluated using a specific method.

I or my legal representative can understand the study and agree to sign the consent.

Exclusion Criteria

Treatment with investigational therapy within 28 days prior to initiation of study treatment

I had major surgery less than 2 weeks ago or my surgical wound has not fully healed.

I have serious heart problems that are not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cabozantinib 40mg orally daily and Atezolizumab 1200mg intravenously on day 1 of each 21-day cycle

12 months

1 visit every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

4 weeks

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 100 months

Treatment Details

Interventions

• Atezolizumab
• Cabozantinib

Trial Overview The study tests a combination of Cabozantinib (a drug that inhibits multiple kinases) and Atezolizumab (an immunotherapy drug) to see if they work better together for NSCLC patients with low PD-L1 expression levels than current therapies.

Participant Groups

Group I: Cabozantinib and Atezolizumab Experimental Treatment 2 Interventions

Cabozantinib 40mg po daily + Atezolizumab 1200mg iv on day 1; 1 cycle = 21 days

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?

Jun Zhang, MD, PhD

Lead Sponsor

Trials

5

Recruited

220+

Genentech, Inc.

Industry 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

Exelixis

Industry Sponsor

Trials

126

Recruited

20,500+

Michael M. Morrissey

Exelixis

Chief Executive Officer since 2010

PhD in Chemistry from Harvard University, BSc in Chemistry from the University of Wisconsin

Vicki L. Goodman

Exelixis

Chief Medical Officer since 2022

MD

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, 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 combined with chemotherapy showed promising efficacy in treating advanced, treatment-naïve non-small-cell lung cancer (NSCLC), with overall response rates of 36% to 68% across different chemotherapy regimens in a study of 76 patients.

The treatment was generally well tolerated, although common severe side effects included neutropenia and anemia, indicating a manageable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. Liu, SV., Camidge, DR., Gettinger, SN., et al.[2022]

Atezolizumab, an immune checkpoint inhibitor, has been shown to significantly prolong overall survival in patients with advanced non-small cell lung cancer (NSCLC) who have previously received chemotherapy, based on results from the phase II POPLAR and phase III OAK trials.

The treatment is particularly effective in patients with higher PD-L1 expression, demonstrating higher objective response rates, and it has a manageable safety profile with a low incidence of immune-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. Blair, HA.[2020]

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]

In a phase 2 study involving 199 treatment-naïve patients with advanced non-squamous non-small-cell lung cancer, the combination of cisplatin, pemetrexed, and bevacizumab (CisPemBev) showed a statistically significant improvement in progression-free survival (PFS) compared to carboplatin, paclitaxel, and bevacizumab (CarPacBev), with a median PFS of 7.6 months versus 7.0 months.

Both treatment regimens were well tolerated, but CisPemBev had a lower incidence of grade ≥3 adverse events (67%) compared to CarPacBev (82%), suggesting it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). Udagawa, H., Sugiyama, E., Harada, T., et al.[2022]

References

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

Atezolizumab: First Global Approval. [2019]

2. England pubmed.ncbi.nlm.nih.gov

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

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

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

4. England pubmed.ncbi.nlm.nih.gov

Long-term survival follow-up of atezolizumab in combination with platinum-based doublet chemotherapy in patients with advanced non-small-cell lung cancer. [2022]

5. France pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Previously Treated Advanced Non-Small Cell Lung Cancer. [2020]

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]

8. China pubmed.ncbi.nlm.nih.gov

Bevacizumab plus platinum-based chemotherapy in advanced non-squamous non-small-cell lung cancer: a randomized, open-label phase 2 study (CLEAR). [2022]