Avelumab for Thymic Cancer

Overseen By Arun Rajan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Hormonal agents

Disqualifiers: Active infection, Autoimmune disease, Brain metastases, 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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 11

Duration: Variable (until progression or intolerable side effects)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if avelumab is safe and effective for treating thymoma or thymic carcinoma, cancers originating in the thymus gland that have returned or worsened after standard chemotherapy. Avelumab may help the immune system fight these cancers. Participants will receive avelumab through an IV every two weeks, along with regular medical tests and scans to monitor their condition. Those whose thymic cancer returned or grew after platinum-based chemotherapy might be suitable for this trial. As a Phase 2 trial, this 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 must stop taking your current medications, but it does mention that you cannot have concurrent treatment with certain drugs, including anticancer treatments, immunosuppressive agents, and hormonal agents for thymic cancer within specific time frames before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that avelumab is likely to be safe for humans?

Research has shown that avelumab is generally safe and well-tolerated in people with thymic cancer. In studies, some patients with recurring thymoma and thymic carcinoma responded positively to avelumab. However, while avelumab works against these cancers, it can cause side effects. Some individuals experience immune-related side effects because avelumab affects the immune system.

Previous patients have taken avelumab without major problems, but careful monitoring remains important. Common side effects may include fatigue, muscle pain, and reactions at the injection site. To lower risks, patients receive medications like diphenhydramine (Benadryl) and acetaminophen (Tylenol) before treatment.

Overall, avelumab has shown promise in treating thymic cancers, but participants should discuss potential risks and benefits with their doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Avelumab is unique because it is an immunotherapy drug that works by targeting and blocking the PD-L1 protein, which helps tumors evade the immune system. Most treatments for thymic cancer, like chemotherapy, attack cancer cells directly but can also harm healthy cells, leading to significant side effects. Avelumab, on the other hand, aims to harness the body's immune system to fight off cancer cells, potentially leading to fewer side effects and more effective long-term control of the disease. Researchers are excited about Avelumab because it represents a shift from traditional treatments, offering a promising new approach that could improve outcomes for patients with thymic cancer.

What evidence suggests that avelumab might be an effective treatment for thymic cancer?

Research shows that avelumab, the treatment under study in this trial, helps the immune system fight cancer by targeting a protein called PD-L1. In previous studies with patients whose thymic cancer had returned, avelumab showed promising results. About 34% of these patients experienced tumor shrinkage. Although no patients saw a complete disappearance of the cancer, this reduction can be important for managing the disease. The treatment has generally been well-tolerated, which is crucial for those considering additional therapy options. ^{1 2 5 6 7}

Who Is on the Research Team?

Arun Rajan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with thymoma or thymic carcinoma that's worsened after platinum chemotherapy can join. They need at least one measurable tumor and good organ/marrow function. They must not be pregnant, agree to use effective contraception, and have an ECOG performance status of 0 or 1 (fully active or restricted in physically strenuous activity but ambulatory).

Inclusion Criteria

My condition cannot be treated with surgery.

I have had PD-1 or PD-L1 therapy without severe side effects or disease worsening.

Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1

Exclusion Criteria

I have brain metastases that are causing symptoms.

Any psychiatric condition that would prohibit the understanding or rendering of informed consent

I haven't taken immunosuppressive drugs in the last 28 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive avelumab intravenously every 2 weeks until disease progression or intolerable side effects

Variable (until progression or intolerable side effects)

Every 2 weeks (in-person)

Assessment

Tumor response assessed every 6 weeks using RECIST criteria; scans and possible biopsy at Cycle 4

Every 6 weeks

Scans every 6 weeks, biopsy at Cycle 4

Follow-up

Participants are monitored for safety and effectiveness after stopping treatment

6 months

2-4 weeks, 10 weeks, and every 3 months after stopping treatment

What Are the Treatments Tested in This Trial?

Interventions

• Avelumab

Trial Overview The trial is testing Avelumab's safety and effectiveness for those whose cancer has returned post-chemotherapy. Participants will receive Avelumab infusions every two weeks, possibly alongside pre-medications like Benadryl and Tylenol to reduce infusion reactions.

How Is the Trial Designed?

Group I: Arm 1 Avelumab Experimental Treatment 1 Intervention

Avelumab will be administered at a dose of 10 mg/kg intravenously once every two weeks until disease progression or development of intolerable adverse events.

Avelumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in United States as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Approved in Japan as Bavencio for:

• Merkel cell carcinoma
• Renal cell carcinoma
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A multicenter phase II study is investigating the combination of atezolizumab (an anti-PD-L1 antibody) with carboplatin and paclitaxel in 47 patients with advanced or recurrent thymic carcinoma, aiming to improve treatment outcomes compared to standard chemotherapy.

The study will assess the safety and efficacy of this combination therapy, with the primary focus on the objective response rate, and will follow patients for up to 2 years to evaluate long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study Design and Rationale for Marble Study: A Phase II Trial of Atezolizumab (MPDL3280A) Plus Carboplatin and Paclitaxel in Patients With Advanced or Recurrent Thymic Carcinoma (JTD2101). Asao, T., Shukuya, T., Mimori, T., et al.[2023]

In a phase I trial involving 8 patients with relapsed thymic epithelial tumors, the anti-PD-L1 antibody avelumab showed anti-tumor activity, with 29% of thymoma patients achieving a confirmed partial response after treatment.

All patients who responded to avelumab experienced immune-related adverse events, indicating that while the treatment can be effective, it may also lead to significant side effects that require management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. Rajan, A., Heery, CR., Thomas, A., et al.[2020]

The combination of pembrolizumab and chemotherapy as a first-line treatment for metastatic thymic carcinoma showed promising results in two cases, with one patient achieving a complete response lasting over 3 years and the other a partial response for 20 months.

This study highlights the potential of pembrolizumab combined with chemotherapy in treating advanced thymic carcinoma, suggesting it may be a viable treatment strategy that deserves further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Robust and durable response to first-line treatment of pembrolizumab combined with chemotherapy in two patients with metastatic thymic squamous cell carcinoma: Case report. Chen, C., Sun, P., Long, J.[2022]

Thymic epithelial tumors (TETs) have a low tumor mutational burden but high PD-L1 expression, making them potential candidates for treatment with immune checkpoint inhibitors (ICIs) like pembrolizumab and avelumab, which have shown reasonable response rates in early clinical trials.

While ICIs may improve outcomes for TET patients, they are associated with a higher incidence of immune-related adverse events compared to other cancers, indicating the need for larger studies to better understand their safety and efficacy in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy for thymoma. Jakopovic, M., Bitar, L., Seiwerth, F., et al.[2021]

In a phase II trial of nivolumab for advanced thymic carcinoma involving 15 patients, three showed long-term stable disease (SD) lasting over 24 weeks, indicating potential efficacy of the treatment.

Biomarker analyses revealed that low levels of FOXP3 and CD204 expression in tumors, along with a higher number of naïve/memory immune cells in patients with long SD, suggest that immune system activation may be crucial for improving treatment outcomes in thymic carcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive biomarker analysis from phase II study of nivolumab in patients with thymic carcinoma. Katsuya, Y., Kitano, S., Yamashita, M., et al.[2023]

In a study of 10 patients with advanced thymic carcinoma, pembrolizumab showed a 22.5% response rate, indicating some efficacy of this immunotherapy in a challenging cancer type.

The research identified potential predictive markers for response to immunotherapy, specifically the expression of PD-L1 and alterations in genes like CYLD and BAP1, which could help select patients who might benefit from anti-PD-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular predictors of response to pembrolizumab in thymic carcinoma. He, Y., Ramesh, A., Gusev, Y., et al.[2022]

In a phase 2 trial involving 32 patients with advanced type B3 thymoma and thymic carcinoma, the combination of avelumab and axitinib showed a 34% overall response rate, indicating promising anti-tumor activity in patients who had previously progressed after chemotherapy.

The treatment was generally well-tolerated, with the most common severe side effect being hypertension (19% of patients), and no treatment-related deaths reported, suggesting that this combination therapy could be a viable new standard treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial. Conforti, F., Zucali, PA., Pala, L., et al.[2022]

The Italian Association of Medical Oncology has established comprehensive, evidence-based recommendations for the clinical management of thymic epithelial tumors, covering diagnosis, staging, and treatment options.

These recommendations include guidance on new systemic treatments, such as targeted therapies and immunotherapies, which are crucial for managing these rare diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM). Conforti, F., Marino, M., Vitolo, V., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6805423/

Efficacy and tolerability of anti-programmed death-ligand 1 ... We sought to evaluate the efficacy and safety of the anti-PD-L1 antibody, avelumab (MSB0010718C), in patients with relapsed, advanced thymic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03076554

NCT03076554 | A Pilot Study to Investigate the Safety and ... Objective: To test if avelumab is safe and well-tolerated, and is effective in treating relapsed or refractory thymoma and thymic carcinoma. Eligibility: People ...

3. onclive.com onclive.com/view/avelumab-and-axitinib-elicits-responses-in-advanced-thymoma-and-thymic-carcinoma

Avelumab and Axitinib Elicits Responses in Advanced ... The results showed that the overall response rate (ORR) was 34% (n = 11/32; 90% CI, 21%-50%). No patients had a complete response, 11 (34%) had ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1470204522005423

Avelumab plus axitinib in unresectable or metastatic type ... Anti-PD-1 and anti-PD-L1 drugs have shown acceptable safety in patients with type B3 thymomas and thymic carcinomas, with response rates ranging from 0 to 23% ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/31639039/

Efficacy and tolerability of anti-programmed death-ligand 1 ... We sought to evaluate the efficacy and safety of the anti-PD-L1 antibody, avelumab (MSB0010718C), in patients with relapsed, advanced thymic ...

6. jto.org jto.org/article/S1556-0864(16)31574-X/fulltext

OA18.03 Safety and Clinical Activity of Avelumab ... Avelumab is active in patients with recurrent thymoma. Strategies need to be developed to reduce the risk of development of irAEs in response to immune ...

7. asco.org asco.org/abstracts-presentations/ABSTRACT169986

Safety and clinical activity of anti-programmed death-ligand ... Results: 8 pts were treated: 7 with thymoma (T) and 1 with thymic carcinoma (TC). Median age 53 yrs (39-76). 3 pts with T (2 B3, 1 B2/B3) received Avelumab ...