Cabozantinib + Atezolizumab for Lung Cancer

(Cabatezo-1 Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining cabozantinib (a drug that blocks certain proteins in cancer cells) with atezolizumab (an immune system booster) can benefit people with non-small cell lung cancer (NSCLC) that hasn't responded well to standard treatments. Researchers are particularly interested in patients whose tumors show low levels of a protein called PD-L1, as these patients often gain little from existing therapies. Individuals with advanced lung cancer unresponsive to other treatments might be suitable for this study. As a Phase 2 trial, the study measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that the safety of cabozantinib and atezolizumab is well-understood. Studies have found that cabozantinib can cause side effects like nausea, vomiting, diarrhea, and high blood pressure. However, these side effects occurred less frequently when combined with atezolizumab.

Atezolizumab also has a known safety profile. Research has not identified any new safety concerns when combined with cabozantinib. In some studies, most patients experienced treatment-related side effects, but these were generally manageable.

Overall, these treatments have been studied enough to understand potential side effects. Joining a trial ensures that these effects will be closely monitored, and the medical team will help manage any issues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cabozantinib and Atezolizumab for lung cancer because it brings a fresh approach to treatment. Most current options, like chemotherapy and radiation, work by directly attacking cancer cells or shrinking tumors. However, Atezolizumab is an immunotherapy that boosts the body's immune system to recognize and fight cancer cells, while Cabozantinib is a tyrosine kinase inhibitor that disrupts cancer cell growth pathways. This dual action not only targets cancer cells directly but also empowers the immune system, potentially leading to more effective and longer-lasting results compared to standard treatments.

What evidence suggests that the combination of cabozantinib and atezolizumab could be an effective treatment for lung cancer?

Research shows that using cabozantinib and atezolizumab together might help people with non-small cell lung cancer (NSCLC) who have low levels of a protein called PD-L1. In this trial, participants will receive the combination of cabozantinib and atezolizumab. Studies have found that cabozantinib can boost the number of immune cells that fight tumors and decrease the cells that weaken the immune system. Specifically, this combination treatment reduced tumor size in 20% of patients. In another study, the treatment delayed cancer growth for about 4.6 months on average. These results offer hope for better treatment outcomes for this challenging group of patients. ^{1 2 3 4 6}

Who Is on the Research Team?

Jun Zhang, MD, PhD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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 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 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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394869/

Analysis of the Efficacy and Safety of Cabozantinib ... A significant finding in our study was the reduction in adverse events, including nausea, vomiting, diarrhea, and high-grade hypertension, when ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.02166

CONTACT-01: A Randomized Phase III Trial of ... Median progression-free survival was 4.6 months (95% CI, 4.1 to 5.6) and 4.0 months (95% CI, 3.1 to 4.4), respectively (stratified HR, 0.74 [95% ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05859217

NCT05859217 | A Study of Combining Cabozantinib and ... Consistent with this, cabozantinib has been shown to increase tumor infiltrative cytotoxic CD8+ T cells, reduce immune suppressive T regulatory cells (Tregs) ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S2666364324000365;

Original Article Cabozantinib Plus Atezolizumab or ... Median (range) follow-up was 26.1 months (12.1–44.2) and 22.4 months (1.5–29.0), respectively. Objective response rate was 20% (95% confidence interval: 11.7%– ...

5. ir.exelixis.com ir.exelixis.com/news-releases/news-release-details/exelixis-provides-update-phase-3-contact-01-trial-evaluating

Exelixis Provides Update on Phase 3 CONTACT-01 Trial ... The overall five-year survival rate for patients with NSCLC is 26%, but that rate falls to just 7% for those with advanced or metastatic disease.4 More than ...

6. jtocrr.org jtocrr.org/article/S2666-3643(24)00036-5/fulltext

Results From the Phase 1b COSMIC-021 Study Treatment-related adverse events (TRAEs) occurred in 86% of patients in the combination cohort and 90% in the single-agent cabozantinib cohort; grade 3/4 TRAEs ...