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Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04417660
Recruitment Status : Recruiting
First Posted : June 5, 2020
Last Update Posted : July 4, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Thymic Epithelial Tumor Recurrent Thymoma Thymic Cancer Drug: M7824 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 38 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II, Open-Label Trial of Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma
Actual Study Start Date : December 26, 2020
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Thymus Cancer

Arm Intervention/treatment
Experimental: Bintrafusp alfa (M7824)
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.
Drug: M7824
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.




Primary Outcome Measures :
  1. Objective response rate [ Time Frame: from the start of the treatment until disease progression/recurrence ]
    overall response rate for M7824 based on RECIST criteria


Secondary Outcome Measures :
  1. Duration of response, progression free survival & overall survival [ Time Frame: from the start of the treatment until disease progression/recurrence ]
    To determine duration of response, progression free survival and overall survival in participants with recurrent thymic epithelial TETs

  2. Safety & tolerability of M7824 [ Time Frame: from the start of the treatment until disease progression/recurrence ]
    To determine the safety and tolerability of 1200 mg M7824 administered once every 2 weeks in participants with thymoma and thymic carcinoma



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • IINCLUSION CRITERIA:
  • Participants must have histologically confirmed (by the pathology department/CCR/NCI) thymoma or thymic carcinoma.
  • Participants must have had at least one prior line of platinum-based chemotherapy. Progressive disease must be documented prior to study entry and participants must have advanced, unresectable disease that is not amenable to surgical resection.
  • Disease must be measurable with at least 1 unidimensional measurable lesion by RECIST 1.1.
  • Participants must be aged >=18 years.
  • ECOG performance status <=1.
  • Participants must have adequate organ and marrow function as defined below:

    • absolute neutrophil count: >= 1,500/mm3 OR >= 1.5 x 10(9)/L
    • platelets: >=> 100,000/mm3 OR >= 100 x 10(9)/L
    • hemoglobin: >= 9g/dL (may have been transfused)
    • total bilirubin: <= the upper limit of normal range (ULN) OR <= 3.0 x ULN for participants with documented metastatic disease to the liver
    • AST(SGOT)/ALT(SGPT): <= 1.5 x ULN OR <= 5 x ULN for subjects with documented metastatic disease to the liver
    • ALP: <= 2.5 x ULN
    • creatinine clearance: >= 60 mL/min/1.73 m2 calculated by calculated using eGRF in the clinical lab
    • INR: normal INR, per institutional guidelines
    • PT: <= 1.5 x ULN
    • aPTT: <= 1.5 x ULN
  • Negative serum or urine pregnancy test at screening for women of childbearing potential (WOCBP). NOTE: WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. If necessary, to confirm postmenopausal status an FSH level will be included at screening. The effects of Bintrafusp alfa on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation and for at least 2 months after the last dose of the drug.
  • Participants with previously treated brain or CNS metastases are eligible provided that the subject has recovered from any acute side effects of radiotherapy and does not require treatment with steroids, and any whole brain radiation therapy was completed at least 2 weeks prior to enrollment.
  • Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to bintrafusp alfa.
  • History of anaphylaxis or recent (within 5 months) history of uncontrollable asthma.
  • Prior treatment with PD-1 or PD-L1-directed immune checkpoint blockade is not permitted. Prior treatment with other immunomodulating drugs such as cancer vaccines is permitted based on investigators discretion as long as treatment was not discontinued due to life-threatening adverse events (laboratory abnormalities alone with prior therapy will not exclude participants from this trial).
  • Concurrent treatment with a non-permitted drug
  • Prior anticancer treatment within 14 days before treatment (e.g., cytoreductive therapy, radiotherapy [with the exception of palliative bone directed radiotherapy], immune therapy, or cytokine therapy except for erythropoietin); major surgery within 14 days before treatment (excluding prior diagnostic biopsy); prior systemic therapy (or 5 half-lives of a drug, whichever is shorter) with immunosuppressive agents within 14 days before treatment; use of hormonal agents for anti-cancer therapy within 7 days before treatment; or use of any investigational drug within 14 days before treatment.

Note: Subjects receiving bisphosphonate or denosumab are eligible provided treatment was initiated at least 14 days before treatment.

  • History of previous malignant disease within the last 3 years with the following exceptions: basal or squamous cell carcinoma in situ of the skin treated with curative intent, endoscopically resected GI cancers limited to the mucosal layer without recurrence in > 1 year, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary or follicular thyroid carcinoma, and superficial/non-muscle invasive bladder cancer.
  • Active brain or CNS metastases causing clinical symptoms or metastases that require therapeutic intervention.
  • Active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent, with the exception of diabetes type I, vitiligo, psoriasis, autoimmune thyroid disease not requiring immunosuppressive treatment, or pure red cell aplasia that are adequately managed with medical therapy. In addition, anti-acetylcholine receptor binding and anti-striational antibodies will be checked during screening and participants will be ineligible if results are positive, even if there is no clinical history of autoimmune disease.
  • Participants receiving systemic corticosteroids at doses > 10 mg daily prednisone equivalent will be excluded. However, participants on inhaled steroids and adrenal replacement steroid doses up to 10 mg daily prednisone equivalents are permitted in the absence of autoimmune disease
  • Active infection requiring systemic therapy or significant acute or chronic infections including, among others:

    • Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive).
    • Known history of testing positive for HIV or testing positive for HIV at screening or known acquired immunodeficiency syndrome.

HIV-positive TET participants are ineligible because of the risk of developing opportunistic infections after treatment with an immune checkpoint inhibitor. Additionally, TET participants are at higher risk of developing opportunistic infections due to underlying immune defects. Prior cases of disseminated herpes virus, cytomegalovirus and fungal infections have been documented in this patient population.

  • Prior organ transplantation including allogenic stem-cell transplantation, Participants who have had prior transplants that do not require immunosuppression are eligible.
  • Persisting toxicity related to prior therapy (NCI CTCAE v. 5 Grade > 1); however, alopecia, sensory neuropathy Grade <= 2, or other Grade <= 2 not constituting a safety risk based on investigator s judgment are acceptable.
  • Participants unwilling to accept blood products as medically indicated.
  • Pregnant or lactating women. Pregnant women are excluded from this study because Bintrafusp alfa is in the class of agents known as antineoplastics/monoclonal antibodies with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Bintrafusp alfa, breastfeeding should be discontinued if the mother is treated with Bintrafusp alfa.
  • Known alcohol or drug abuse.
  • Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, cerebral vascular accident/stroke < 6 months prior to enrollment, myocardial infarction < 6 months prior to enrollment, or psychiatric illness/social situations that would limit compliance with study requirements. All other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, drug-induced pneumonitis requiring oral or IV steroids, interstitial lung disease, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study. Participants with history of bleeding diathesis or recent major bleeding events considered by the Investigator as high risk for investigational drug treatment are also excluded.
  • Administration of live vaccine within 4 weeks prior to treatment, with the exception of vaccination against COVID-19

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04417660


Contacts
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Contact: Shannon G Swift, R.N. (240) 858-3157 shannon.swift@nih.gov
Contact: Arun Rajan, M.D. (240) 760-6236 rajana@mail.nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Arun Rajan, M.D. National Cancer Institute (NCI)
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04417660    
Other Study ID Numbers: 200097
20-C-0097
First Posted: June 5, 2020    Key Record Dates
Last Update Posted: July 4, 2022
Last Verified: April 29, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: .All IPD recorded in the medical record will be shared with intramural investigators upon request. In addition, all large scale genomic sequencing data will be shared with subscribers to dbGaP.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Time Frame: Clinical data available during the study and indefinitely. Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. Genomic data are made available via dbGaP through requests to the data custodians.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Thymoma
thymic cancer
Immune Checkpoint Inhibition
programmed death ligand 1 (PD-L1)
Additional relevant MeSH terms:
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Thymoma
Thymus Neoplasms
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Complex and Mixed
Thoracic Neoplasms
Neoplasms by Site
Lymphatic Diseases