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

Disqualifiers: Autoimmune disease, Active infection, 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

Compensation: Varies

Number of Visits: 2

Duration: Variable (until disease progression or intolerable adverse events)

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new medication, bintrafusp alfa (also known as M7824), can effectively treat thymoma and thymic carcinoma, two types of cancer affecting the thymus. The goal is to assist patients whose cancer has returned or worsened after standard platinum-based chemotherapy. Suitable participants include those with thymic cancer that has progressed despite prior chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that bintrafusp alfa (M7824) is likely to be safe for humans?

Research shows that bintrafusp alfa has promising effects against tumors, with generally manageable safety. A study on patients with other types of gastrointestinal tumors found that side effects were usually tolerable. Although some patients experienced side effects, these were not typically severe enough to stop treatment.

This trial is in an intermediate phase, indicating some evidence of safety, but more research is needed to fully understand tolerability. For specific concerns, discussing them with the clinical trial team is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Bintrafusp alfa is unique because it combines two powerful mechanisms in one treatment. Unlike traditional therapies for thymic cancer, which often involve chemotherapy or radiation, Bintrafusp alfa merges a TGF-beta trap with a PD-L1 inhibitor. This dual action not only helps to block cancer cell growth but also enhances the immune system's ability to attack the tumor. Researchers are excited about this treatment because it has the potential to be more effective with fewer side effects compared to current options.

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

Research has shown that bintrafusp alfa (M7824), the investigational treatment in this trial, has promising effects in treating thymic cancer. Early studies indicate that this drug can help patients whose cancer has returned after treatments like chemotherapy. Bintrafusp alfa is a type of protein that blocks certain pathways cancer cells use to grow, potentially stopping the cancer from spreading. Although more research is needed, these initial findings suggest that bintrafusp alfa could be a helpful option for people with thymic cancer. ^{1 2 3 4 5}

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 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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bintrafusp Alfa (M7824)

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

In a phase I trial involving 31 heavily pretreated Asian patients with advanced gastric/gastroesophageal junction cancer, bintrafusp alfa showed a manageable safety profile, with 19% experiencing grade 3 treatment-related adverse events and no grade 4 events reported.

The treatment demonstrated clinical activity, with a confirmed objective response rate of 16% and a disease control rate of 26%, suggesting potential effectiveness regardless of PD-L1 expression or microsatellite instability status.

NCBI (Pubmed)

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. Kang, YK., Bang, YJ., Kondo, S., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36382087/

Bintrafusp alfa, an anti-PD-L1:TGF-β trap fusion protein, in ... Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04417660?term=AREA%5BBasicSearch%5D(M7824)&rank=3

Bintrafusp Alfa (M7824) in Subjects With Thymoma and ... 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.

3. researchgate.net researchgate.net/publication/392302338_Efficacy_of_bintrafusp_alfa_M7824_in_patients_with_gastrointestinal_tumors_A_meta-analysis

Efficacy of bintrafusp alfa (M7824) in patients with ... e16077 Background: This meta-analysis aims to evaluate the efficacy and safety of Bintrafusp Alfa (M7824) in patients with gastrointestinal tumors.

4. sciencedirect.com sciencedirect.com/science/article/pii/S235239642200562X

The difficulty in translating the preclinical success of ... For example, early data are now available from 39 patients with pre-treated, recurrent/metastatic cervical cancer receiving Bintrafusp alfa. This cohort was ...

5. withpower.com withpower.com/trial/phase-3-thymus-neoplasms-11-2020-8504c

Bintrafusp Alfa for Thymic Cancer What data supports the effectiveness of the drug Bintrafusp Alfa for thymic cancer? Bintrafusp Alfa has shown promising antitumor activity and manageable ...