Bintrafusp Alfa 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: PD-1, PD-L1, Steroids, others

Disqualifiers: Autoimmune disease, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Background: Thymoma and thymic carcinoma are diseases of the thymus. Platinum-based chemotherapy is the standard treatment for these diseases. But in many cases, the disease returns after treatment. Researchers want to see if a new drug can help. Objective: To see if bintrafusp alfa (M7824) is an effective treatment for thymoma and thymic carcinoma. Eligibility: People age 18 and older who have thymoma or thymic cancer and their disease returned or progressed after treatment with at least one platinum-containing chemotherapy treatment plan. Design: Participants will be screened under a separate protocol. Their medical, medicine, and treatment history will be reviewed. They will have a tumor biopsy if they do not have a sample. Participants will get the study drug once every 2 weeks as an intravenous infusion. For this, a small plastic tube is put into an arm vein. During the study, participants will undergo the following: Medicine review Physical exam Review of their symptoms and their ability to perform their normal activities Blood and urine tests Thigh muscle scan (using MRI) Tumor assessment (using MRI or CT) Heart and lung function tests Thyroid gland test Skin assessment. Participants may have tumor biopsies. Some of their blood and biopsy samples will be used for gene testing. Participants may take the study drug until their disease worsens or they cannot tolerate treatment. Participants will have follow-up visits 2 and 6 weeks after stopping treatment. Then they will have long-term follow-up visits every 3 months. These may include imaging scans. Visits may be done by phone, with scans (if needed) done at their doctor s office.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had prior anticancer treatment within 14 days before starting the trial, and certain treatments like systemic corticosteroids above a specific dose are not allowed. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Bintrafusp Alfa for thymic cancer?

Bintrafusp Alfa has shown promising antitumor activity and manageable safety in various cancer types, including non-small cell lung cancer and gastric cancer, suggesting it might be effective for thymic cancer as well. ^{1 2 3 4 5}

Is Bintrafusp Alfa safe for humans?

Bintrafusp Alfa has been tested in various cancer types, including lung and esophageal cancer, and has shown manageable safety, meaning that while there may be side effects, they are generally considered controllable. ^{1 2 3 4 6}

What makes the drug Bintrafusp Alfa unique for treating thymic cancer?

Bintrafusp Alfa is unique because it combines two actions in one drug: it blocks PD-L1, a protein that helps cancer cells hide from the immune system, and traps TGF-β, a molecule that can suppress the immune response. This dual action is designed to enhance the body's ability to fight cancer more effectively than treatments targeting only one of these pathways. ^{1 2 3 4 7}

Research Team

Arun Rajan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

Adults aged 18+ with thymoma or thymic carcinoma that has returned or progressed after platinum-based chemotherapy. They must have measurable disease, adequate organ and marrow function, no severe autoimmune diseases, no recent major surgeries or use of certain drugs, and not be pregnant.

Inclusion Criteria

My organs and bone marrow are functioning well.

- ALP: <= 2.5 x ULN

I have had platinum-based chemotherapy before.

Exclusion Criteria

I have not had major surgery in the last 14 days.

Pregnant or lactating women

I have tested positive for HIV or have AIDS.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bintrafusp alfa intravenously every 2 weeks until disease progression or intolerable adverse events

Variable (until disease progression or intolerable adverse events)

Bi-weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits 2 and 6 weeks after stopping treatment, then every 3 months

Long-term

2 visits (in-person) after stopping treatment, then every 3 months (phone or in-person)

Optional Treatment Discontinuation

Participants with ongoing response or disease stability after 12 months may discontinue treatment with an option to reinstitute if disease activity is noted

After 12 months of treatment

Treatment Details

Interventions

• Bintrafusp Alfa (M7824) (Bifunctional Fusion Protein)

Trial Overview The trial is testing bintrafusp alfa (M7824), a new drug for thymoma and thymic carcinoma. Participants will receive the drug every two weeks via IV infusion and undergo regular health assessments including blood tests, scans, heart/lung/thyroid function tests, and possibly biopsies.

Participant Groups

Group I: Bintrafusp alfa (M7824) Experimental Treatment 1 Intervention

Bintrafusp alfa will be administered at a dose of 1200 mg intravenously once every two weeks until disease progression or development of intolerable adverse events.

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 3 trial involving 304 patients with PD-L1-high advanced NSCLC, bintrafusp alfa did not show superior efficacy compared to pembrolizumab, with similar progression-free survival and overall survival rates.

Bintrafusp alfa was associated with a higher rate of treatment-related adverse events, with 42.4% of patients experiencing grade 3-4 side effects compared to only 13.2% for pembrolizumab, leading to the study's discontinuation at an interim analysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial. Cho, BC., Lee, JS., Wu, YL., et al.[2023]

In a study involving 83 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone anti-PD-(L)1 therapy, bintrafusp alfa demonstrated a modest objective response rate of 4.8%, indicating some clinical activity despite not meeting the primary endpoint.

The treatment was generally well-tolerated, with 22.9% of patients experiencing grade ≥3 treatment-related adverse events, suggesting a manageable safety profile for this heavily pretreated patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. Barlesi, F., Isambert, N., Felip, E., et al.[2023]

In a study of 80 patients with advanced non-small cell lung cancer (NSCLC) who had previously undergone platinum-based therapy, bintrafusp alfa demonstrated an overall response rate (ORR) of 21.3%, with higher efficacy observed in patients with PD-L1-positive tumors (36.0% ORR) and those with high PD-L1 expression (85.7% ORR).

The treatment was generally well-tolerated, with 69% of patients experiencing treatment-related adverse events, but only 10% discontinuing treatment due to these events, indicating that bintrafusp alfa has a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial. Paz-Ares, L., Kim, TM., Vicente, D., et al.[2023]

Bintrafusp alfa, a novel treatment for solid tumors, has shown promising antitumor activity and manageable safety in a study involving 644 patients, supporting its potential as an effective therapy.

The pharmacokinetic analysis suggests that a flat dosing regimen (1200 mg every 2 weeks) is preferable, as it results in less variability in drug exposure compared to weight-based dosing, with no significant dosage adjustments needed based on patient characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. Wilkins, JJ., Vugmeyster, Y., Dussault, I., et al.[2020]

In a phase 1 study involving 30 patients with advanced esophageal adenocarcinoma, bintrafusp alfa demonstrated a confirmed objective response rate of 20%, indicating potential efficacy in this heavily pretreated population.

The treatment was generally well-tolerated, with 63.3% of patients experiencing treatment-related adverse events, but no grade 4 events or treatment-related deaths were reported, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. Tan, B., Khattak, A., Felip, E., et al.[2022]

Bintrafusp alfa (BA) effectively enhances antitumor activity by simultaneously targeting PD-L1 and TGF-β in the tumor microenvironment, leading to a significant increase in binding affinity and improved T cell activation compared to traditional therapies.

BA induces distinct changes in the tumor microenvironment, including upregulation of immune-related gene signatures and reduction of TGF-β-regulated pathways, resulting in superior antitumor responses over standard combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses. Lan, Y., Yeung, TL., Huang, H., et al.[2022]

References

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

Bintrafusp Alfa Versus Pembrolizumab in Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced NSCLC: A Randomized, Open-Label, Phase 3 Trial. [2023]

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

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients With Non-Small Cell Lung Cancer Resistant or Refractory to Immune Checkpoint Inhibitors. [2023]

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

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Second-Line Treatment of Patients With NSCLC: Results From an Expansion Cohort of a Phase 1 Trial. [2023]

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

Population Pharmacokinetic Analysis of Bintrafusp Alfa in Different Cancer Types. [2020]

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

Safety and Tolerability of Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Asian Patients with Pretreated Recurrent or Refractory Gastric Cancer. [2021]

6. France pubmed.ncbi.nlm.nih.gov

Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1, in Patients with Esophageal Adenocarcinoma: Results from a Phase 1 Cohort. [2022]

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

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses. [2022]