A Phase II Study of MEDI4736 (Durvalumab) Plus Tremelimumab as Therapy for Patients With Previously Treated Anti-PD-1/PD-L1 Resistant Stage IV Squamous Cell Lung Cancer (Lung-Map Non-Match Sub-Study)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 2,035
- 主要终点
- Objective Response Rate
研究概览
简要总结
This phase II trial studies how well durvalumab and tremelimumab works in treating patients with stage IV lung cancer that has come back after previous treatment. Monoclonal antibodies, such as durvalumab and tremelimumab, may interfere with the ability of tumor cells to grow and spread.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the objective response rate (confirmed and unconfirmed, complete and partial) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 among patients treated with durvalumab (MEDI4736) plus tremelimumab.
SECONDARY OBJECTIVES:
I. To estimate the duration of response (DoR) among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.
II. To estimate the duration of response (DoR) per immune-related response criteria among patients who achieve a complete response (CR) or partial response (PR) (confirmed and unconfirmed) by RECIST 1.1.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have been assigned to S1400F
- •Patients must have progressed during or after prior platinum-based chemotherapy; patients whose only prior platinum-based chemotherapy regimen was for stage I-III disease (i.e. patient has not received any platinum-based chemotherapy for stage IV or recurrent disease), disease progression on platinum-based chemotherapy must have occurred within one year from the last date that patient received that therapy; patients must have experienced disease progression during or after prior anti-PD-1 or anti-PD-L1 antibody monotherapy as their most recent line of treatment; prior PD-1/PD-L1 combination therapy is not permitted
- •Prior exposure to CTLA-4 inhibitors (ipilimumab and tremelimumab) is not permitted; prior exposure to the following is allowed: attenuated vaccines, anti-EGFR agents, and granulocyte-macrophage colony-stimulating factor (GM-CSF)
- •Patients must not have received nitrosoureas or mitomycin-C within 42 days prior to sub-study registration
- •Patients must not have any prior documented autoimmune or inflammatory disease (including inflammatory bowel disease, diverticulitis with the exception of diverticulosis, celiac disease, irritable bowel disease; Wegner syndrome; Hashimoto syndrome) within 3 years prior to sub-study registration; patients with vitiligo, immune-mediated alopecia, Grave?s disease, or psoriasis requiring systemic treatment within the past 2 years are not eligible; patients with hypothyroidism (e.g. post Hashimoto syndrome) who are stable on hormone replacement therapy are eligible
- •Patients must not have any history of primary immunodeficiency
- •Patients must not have received any immunosuppressive medication within 28 days prior to sub-study registration and must not be planning to receive these medications while on protocol therapy; systemic corticosteroids must be stopped at least 24 hours prior to sub-study registration; however, intranasal and inhaled corticosteroids are allowed at any time before and during protocol therapy
- •Patients must not have experienced a grade 3 or worse immune-related adverse event (irAE) (except asymptomatic nonbullous/nonexfoliative rash) or any unresolved irAE grade 2, nor have experienced a toxicity that led to permanent discontinuation of prior anti-PD-1/PD-L1 immunotherapy
- •Patients must not have any history of organ transplant that requires use of immunosuppressives
- •Patients must not have any known allergy or reaction to any component of the durvalumab (MEDI4736) and/or tremelimumab formulation
- •Patients must not have clinical signs or symptoms of active tuberculosis infection
- •Patients must not have received a live attenuated vaccination within 28 days prior to sub-study registration
- •Patients must not have known human immunodeficiency virus (HIV), or a known positive test for hepatitis B virus surface antigen (HBV sAg), or hepatitis C virus ribonucleic acid (HCV antibody) indicating current acute or chronic infection; patients with a positive hepatitis C antibody with a negative viral load are allowed
- •Patients must have a thyroid-stimulating hormone (TSH) with reflex free T3/free T4 (if TSH is out of normal range) and electrocardiogram (EKG) obtained within 7 days prior to sub-study registration
- •Patients must also be offered participation in banking and in the correlative studies for collection and future use of specimens
排除标准
- 未提供
结局指标
主要结局
Objective Response Rate
时间窗: From date of registration to progression or treatment discontinuation, up to 2 years and 5.5 months.
Percentage of participants with confirmed or unconfirmed, complete or partial response to treatment with MEDI4736 (durvalumab) plus tremelimumab per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1). Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to \< 1.0 cm. All disease must be assessed using the same technique as baseline. Partial Response (PR): Applies only to patients with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.
次要结局
- Duration of Response (DoR) Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1.(From date of registration to maximum of 2 years and 5.5 months or death.)
- Duration of Response (DoR) Per Immune-related Response Criteria Among Patients Who Achieve a Complete Response (CR) or Partial Response (PR) (Confirmed and Unconfirmed) by RECIST 1.1(From date of registration to maximum of 2 years and 5.5 months or death)
- Overall Survival (OS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab(Date of registration to maximum of 2 years and 5.5 months or death.)
- Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs(Duration of treatment and follow up until death or 2 years and 5.5 months post registration)
- Investigator-assessed Progression-free Survival (IA-PFS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab.(From date of registration to maximum 2 years and 5.5 months or death.)
- Investigator-assessed Progression-free Survival (IA-PFS) Assessed by Immune-related Response Criteria (irRC-IA-PFS) Among Patients Treated With MEDI4736 (Durvalumab) Plus Tremelimumab(Date of registration to maximum of 2 years and 5.5 months or death)