Atezolizumab + Chemotherapy for Thyroid Cancer

Overseen By Maria E. Cabanillas, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Corticosteroids, Anti-PD-1, Anti-PD-L1, others

Disqualifiers: Autoimmune disease, Liver disease, HIV, 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: 21

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of combining atezolizumab, an immunotherapy drug, with chemotherapy for certain types of thyroid cancer. It aims to determine if this new approach is more effective than standard treatments for anaplastic or poorly differentiated thyroid cancer, which are aggressive forms of the disease. The trial includes several groups testing different drug combinations, such as atezolizumab with nab-paclitaxel (a form of chemotherapy) or cobimetinib. Suitable participants have thyroid cancer that cannot be surgically removed, has spread, or they have opted against surgery or radiation. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, the use of corticosteroids is not allowed for 10 days before starting atezolizumab, except for certain cases like physiological replacement. 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 has shown that the drug atezolizumab has been tested with other medications, each yielding different safety results. When combined with paclitaxel, atezolizumab can cause immune-related side effects, sometimes leading the body to attack its own organs and tissues. Thyroid problems have been reported but are very rare, affecting less than 0.1% of patients. Atezolizumab has also been combined with nab-paclitaxel for certain breast cancers, suggesting it is somewhat safe.

In another study, the combination of cobimetinib with atezolizumab also led to some immune-related side effects, similar to other combinations. Thyroid issues are a known risk but are generally uncommon. This combination has shown effectiveness in some cancers, indicating that the benefits might outweigh the risks for some patients.

Lastly, the combination of atezolizumab with bevacizumab has been studied for lung cancer treatment. Common side effects include immune-related thyroid issues, but these are rare. Overall, data suggests these treatments are generally well tolerated, though serious side effects can occur in some patients.

This trial is a phase 2 study, meaning the drugs are still being tested mainly for efficacy, but there is already some evidence of their safety in different combinations and conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for thyroid cancer because they integrate atezolizumab, an immune checkpoint inhibitor that boosts the body's immune response against cancer cells. Combined with chemotherapy agents like paclitaxel, this approach aims to enhance the effectiveness of treatment beyond the traditional options, which often rely solely on radioactive iodine or surgery. Additionally, some arms of this trial explore combining atezolizumab with other agents like cobimetinib and bevacizumab, which might further inhibit tumor growth by targeting different cancer pathways. These combinations offer a novel strategy that could potentially improve outcomes for patients by not only attacking the cancer directly but also by enhancing the immune system's ability to fight it.

What evidence suggests that this trial's treatments could be effective for thyroid cancer?

This trial will evaluate the effectiveness of different combinations of atezolizumab with other treatments for thyroid cancer. Studies have shown that combining atezolizumab with nab-paclitaxel, which participants in Cohort IV may receive, resulted in 56% of patients controlling their disease. In Cohort II, participants will receive atezolizumab with cobimetinib, a combination that has helped patients with specific genetic changes live longer. Cohort III will explore the combination of atezolizumab with bevacizumab, which has led to partial tumor shrinkage in up to 40% of patients. Lastly, Cohort I will test the combination of vemurafenib, cobimetinib, and atezolizumab, which has been effective, especially for patients with certain genetic profiles, sometimes allowing for complete tumor removal. These combinations show potential in improving treatment for difficult cases like anaplastic thyroid cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Maria E. Cabanillas, M.D.

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with anaplastic or poorly differentiated thyroid cancer that can't be removed by surgery or has spread. They must have proper kidney and liver function, not be pregnant, agree to use contraception, and have no autoimmune diseases. People who've had certain previous cancer treatments or have serious heart conditions, uncontrolled hypertension, active hepatitis or HIV are excluded.

Inclusion Criteria

I can perform all self-care but cannot work.

Ability to provide informed consent

I have a measurable thyroid cancer lesion, unless I have anaplastic thyroid cancer.

Exclusion Criteria

I do not have eye conditions that exclude me from cohorts 1 and 2.

I do not have a history of serious heart problems, including specific heart rhythm issues.

You have HIV, active hepatitis B, or hepatitis C infections. If you had hepatitis B in the past, you can join the study, but you will need to be watched closely by a specialist. If you have hepatitis C antibodies, you can join only if a specific test is negative.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atezolizumab in combination with chemotherapy based on cohort assignment. Treatment cycles repeat every 21 or 28 days depending on the cohort.

Up to 5 years

Visits every 21 or 28 days for treatment administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up occurs every 3 months for the first 2 years, every 6 months for years 3-4, and then yearly thereafter.

5 years

Regular follow-up visits as per schedule

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bevacizumab
• Cobimetinib
• Nab-paclitaxel
• Paclitaxel
• Vemurafenib

Trial Overview The study tests if atezolizumab combined with chemotherapy (paclitaxel, nab-paclitaxel) and targeted drugs (vemurafenib, cobimetinib) improves outcomes in thyroid cancer compared to standard treatments. It examines how well these drugs work together to stop cancer growth by targeting specific enzymes and boosting the immune system's response.

How Is the Trial Designed?

Group I: Cohort IV (nab-paclitaxel, atezolizumab, paclitaxel,) Experimental Treatment 3 Interventions

Patients receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 and atezolizumab IV on day 1 over 30-60 minutes. Patients may receive paclitaxel IV over 30 minutes on day 1 as a substitute for nab-paclitaxel. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Group II: Cohort III (atezolizumab, bevacizumab) Experimental Treatment 2 Interventions

Patients receive atezolizumab IV over 30-60 minutes and bevacizumab IV over 60-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression and unacceptable toxicity.

Group III: Cohort II (atezolizumab, cobimetinib) Experimental Treatment 2 Interventions

Patients receive cobimetinib PO QD on days 1-21 and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

Group IV: Cohort I (vemurafenib, cobimetinib, atezolizumab) Experimental Treatment 3 Interventions

Patients receive vemurafenib PO BID on days 1-21, cobimetinib PO QD on days 1-21, and atezolizumab IV over 30-60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression and unacceptable toxicity.

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?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

Atezolizumab combined with nab-paclitaxel has been approved by the FDA for treating patients with locally advanced or metastatic triple-negative breast cancer that expresses PD-L1.

This combination therapy is significant as it is the first immunotherapy regimen to receive marketing authorization for any form of breast cancer, marking a new treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab Combo Approved for PD-L1-positive TNBC. [2020]

Atezolizumab, when used with nab-paclitaxel for treating triple negative breast cancer, can cause rare side effects like autoimmune hemolytic anemia, as seen in a case study of a 59-year-old female patient.

The patient's hemolytic anemia was effectively managed with a high-dose prednisone taper, allowing her to continue her cancer treatment without further complications through multiple cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-induced hemolytic anemia - A case report. Younce, CM., Lawton, JM., Patel, DR.[2021]

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]

The ANTELOPE trial is a phase II study comparing the efficacy of a pemetrexed-free regimen (atezolizumab, carboplatin, and nab-paclitaxel) against a pemetrexed-based regimen (pembrolizumab, cis-/carboplatin, and pemetrexed) in treating TTF-1 negative non-small cell lung adenocarcinoma (NSCLC/ADC).

This trial aims to enroll 136 participants across 30 sites in Germany, focusing on overall survival as the primary endpoint, which will help determine the best treatment approach for this specific patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and Design of the Phase II ANTELOPE Study of Atezolizumab, Carboplatin and nab-Paclitaxel vs. Pembrolizumab, Platinum and Pemetrexed in TTF-1 Negative, Metastatic Lung Adenocarcinoma (AIO-TRK-0122). Frost, N., Bleckmann, A., Griesinger, F., et al.[2023]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10857827/

Thyroid Dysfunction after Atezolizumab and Bevacizumab ... In the IMbrave150 trial, 15.5% of patients have been reported to develop thyroid dysfunction after atezolizumab and bevacizumab (Ate/Bev) treatment. However, ...

2. tecentriq-hcp.com tecentriq-hcp.com/hcc/efficacy/key-secondary-endpoints-orr.html

IMbrave150 efficacy results: Key secondary endpoints - ORR TECENTRIQ can cause immune-mediated thyroid disorders. · Thyroiditis occurred in 0.2% (4/2616) of patients receiving TECENTRIQ alone, including Grade 2 (<0.1%) ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0305737225001641

Effectiveness of immune checkpoint inhibitor therapy in ... Efficacy outcomes. Of the 3 studies that reported BOR, partial response was the best response observed with rates varying by tumour type from 0 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10064459/

Thyroid dysfunction with atezolizumab plus bevacizumab ... Of patients treated with only lenvatinib or atezolizumab plus bevacizumab, 2/18 (11%) and 4/15 (27%) developed thyroid dysfunction, respectively ...

5. nature.com nature.com/articles/s41392-025-02427-0

Transarterial chemoembolization plus atezolizumab and ... Among the 45 patients, three (7%) achieved complete response, 18 (40%) had partial response, 23 (51%) showed stable disease, and one (2%) ...

6. tecentriq-hcp.com tecentriq-hcp.com/hcc/dosing-and-administration/dosing.html

Dosing - TECENTRIQ-HCP.com Important Safety Information · TECENTRIQ can cause immune-mediated thyroid disorders. · Thyroiditis occurred in 0.2% (4/2616) of patients receiving TECENTRIQ ...

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2019/761034s021lbl.pdf

Atezolizumab - accessdata.fda.gov The safety of TECENTRIQ with bevacizumab, paclitaxel and carboplatin was evaluated in ... The most common side effects of TECENTRIQ when used in lung cancer with ...

8. tecentriq.com tecentriq.com/hybreza/side-effects/important-safety-information.html

Important Safety Information | TECENTRIQ HYBREZA ... Learn about the safety of TECENTRIQ HYBREZA™ (atezolizumab and hyaluronidase-tqjs) for certain kinds of cancer. See full safety for more information.

9. tecentriq-hcp.com tecentriq-hcp.com/hcc/efficacy/exploratory-analysis-risk-status.html

IMbrave150 Exploratory Analysis - Risk Status TECENTRIQ can cause immune-mediated thyroid disorders. · Thyroiditis occurred in 0.2% (4/2616) of patients receiving TECENTRIQ alone, including Grade 2 (<0.1%) ...