Avelumab for Thymic Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Arun Rajan, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Hormonal agents

Disqualifiers: Active infection, Autoimmune disease, Brain metastases, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

Background: Thymoma and thymic carcinoma are cancers originating in the thymus gland. Platinum-based chemotherapy is standard treatment for them. But not uncommonly, the disease returns and people need more treatment to keep the cancer from growing. The drug Avelumab could help the immune system fight cancer. Objective: To test if avelumab is safe and well-tolerated, and is effective in treating relapsed or refractory thymoma and thymic carcinoma. Eligibility: People ages 18 and older with thymoma or thymic carcinoma that has returned or progressed after platinum-containing chemotherapy Design: Participants will be screened with: * Blood, urine, and heart tests * Scan: They lie in a machine that takes pictures of the body. * Physical exam * Medical history * Biopsy: a needle removes a piece of tumor. Samples can be from a previous procedure, although it is desirable to undergo a new biopsy. Participants will have treatment in 2-week cycles. They will continue until the side effects are not tolerable or their disease gets worse. Visits at the following time points are required per protocol. Patients who respond to treatment or have durable stability after at least 12 months of therapy may undergo a dose de-escalation regimen to continue on therapy. * Every 2 weeks: Participants will get avelumab by infusion in a vein (IV). They will get diphenhydramine (benadryl) and acetaminophen (tylenol) by mouth or IV before receiving avelumab to decrease the chances of developing a reaction to avelumab. They will have blood, urine, and heart tests periodically. * Cycles 4 and 7, then every 6 weeks: Scans will be performed to look for shrinkage or growth of tumor. * Cycle 4: Participants will be offered a chance to undergo a biopsy. * 2-4 weeks after stopping treatment: Blood, urine, and heart tests will be performed. Participants might undergo a scan. * 10 weeks after stopping treatment: Blood, urine, and heart tests. * About 6 months after stopping treatment, then every 3 months: Participants will have scans andcan allow genetic testing on their blood and tissue samples.

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.

What data supports the effectiveness of the drug Avelumab for thymic cancer?

Research shows that Avelumab, an anti-PD-L1 antibody, has been effective in treating advanced thymic epithelial tumors, with studies indicating reasonable response rates and progression-free survival. High PD-L1 expression on tumor cells is a predictor of response, making Avelumab a promising option for thymic cancer treatment. ^{1 2 3 4 5}

Is Avelumab safe for use in humans?

Avelumab has been studied in patients with thymic cancer and other conditions, showing reasonable response rates. However, patients with thymic epithelial tumors experienced a higher incidence of immune-related side effects compared to those with other cancers, indicating a need for further research to fully understand its safety profile. ^{1 2 3 4 6}

How is the drug Avelumab unique in treating thymic cancer?

Avelumab is unique for treating thymic cancer because it is an immune checkpoint inhibitor that targets the PD-L1 pathway, which is highly expressed in thymic tumors, making it a promising option despite the lack of standard treatments for this rare cancer. ^{1 2 3 7 8}

Research Team

Arun Rajan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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.

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

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

Trial Timeline

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

Treatment Details

Interventions

• Avelumab (Monoclonal Antibodies)

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.

Participant Groups

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 Japan for the following indications:

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+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

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]

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 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]

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]

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 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]

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]

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]

References

1. England 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. [2022]

2. China pubmed.ncbi.nlm.nih.gov

Immunotherapy for thymoma. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of anti-programmed death-ligand 1 (PD-L1) antibody (Avelumab) treatment in advanced thymoma. [2020]

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

Molecular predictors of response to pembrolizumab in thymic carcinoma. [2022]

5. United States 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). [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Comprehensive biomarker analysis from phase II study of nivolumab in patients with thymic carcinoma. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM). [2021]

8. Switzerland 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. [2022]