A Phase II, Open-Label Trial of Bintrafusp Alfa (M7824) in Subjects With Thymoma and Thymic Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Objective response rate
研究概览
简要总结
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.
详细描述
Background
Platinum-based chemotherapy is the standard of care for advanced unresectable thymic epithelial tumors (TETs). However more than half of these patients experience disease recurrence and require second-line therapy.
There are no approved drugs for treatment of recurrent thymoma and thymic carcinoma and new therapeutic options are needed for patients who have disease progression on or after platinum-containing therapy.
We have demonstrated the safety and clinical activity of immune checkpoint inhibition in patients with recurrent TETs. In an ongoing trial (NCT03076554) we have shown that avelumab, an anti-programmed death ligand-1 (PD-L1) antibody, induces major responses and has an acceptable safety profile.
Combination immunotherapy is under evaluation for treatment of various cancers but has not been studied for the treatment of TETs. Immunotherapy targeting the PD-1/PD-L1 axis can be combined with other immune checkpoint inhibitors, cancer vaccines and anti-cytokine therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 RECIST1.
- •Participants must be aged >=18 years.
- •ECOG performance status <=
- •Participants must have adequate organ and marrow function as defined below:
- •absolute neutrophil count: >= 1,500/mm^3 OR >= 1.5 x 10^9/L
- •platelets: >=> 100,000/mm^3 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 participants with documented metastatic disease to the liver
- •ALP: <= 2.5 x ULN
- •creatinine clearance: >= 60 mL/min/1.73 m^2 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 individuals of childbearing potential (IOCBP). NOTE: IOCBP is defined as any individual 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, individuals of childbearing potential and those that can father children 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 participant 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 participant to understand and the willingness to sign a written informed consent document.
排除标准
- •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: Participants 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 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 individuals. Pregnant individuals 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 individual 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
研究组 & 干预措施
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.
干预措施: M7824 (Drug)
结局指标
主要结局
Objective response rate
时间窗: from the start of the treatment until disease progression/recurrence
overall response rate for M7824 based on RECIST criteria
次要结局
- Duration of response, progression free survival & overall survival(from the start of the treatment until disease progression/recurrence)
- Safety & tolerability of M7824(from the start of the treatment until disease progression/recurrence)