NEO-COMBAT XL: Neoadjuvant and Maintenance XL092 and Cemiplimab in BRAF V600E-wildtype Anaplastic Thyroid Cancer: a Phase 1B Study
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 4
- 主要终点
- Complete gross resection
研究概览
简要总结
This multicenter study examines the safety and feasibility of the combination of neoadjuvant XL092 and cemiplimab prior to surgical resection in participants with wild-type (WT) anaplastic thyroid cancer (ATC) that has a BRAF mutation (BRAF V600E).
详细描述
This study includes subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their standard of care. The study hypothesizes that the combination of neoadjuvant XL092 and cemiplimab will be safe and feasible prior to surgical resection in participants with BRAF V600E-WT ATC.
Anaplastic thyroid cancer (ATC) is a highly aggressive and fatal malignancy. For patients with BRAF V600E-wildtype ATC, chemotherapy, whether as a single agent or in combination, remains the standard treatment despite its low response rates. Studies have shown that while immunotherapy (IO) and receptor tyrosine kinase inhibitor (TKI) monotherapy are safe for these patients, their efficacy as single agents is limited.
This study addresses a significant unmet need and is based on the strong synergy observed between IO and TKI in clinical studies of other cancers. It includes subjects with BRAF V600E-wildtype ATC who are scheduled for surgical resection as part of their standard care. The study hypothesizes that the combination of neoadjuvant XL092 and cemiplimab will be safe and feasible before surgical resection in these patients.
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
- •Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information.
- •Subjects are willing and able to comply with study procedures based on the judgment of the investigator.
- •Age ≥ 18 years at the time of consent.
- •the Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-
- •Pathologic findings supporting the clinical impression of anaplastic thyroid cancer. Terminology consistent or suggestive of diagnosis may include the following: anaplastic thyroid carcinoma, undifferentiated carcinoma, squamous carcinoma; carcinoma with spindled, giant cell, or epithelial features; poorly differentiated carcinoma with pleomorphism, extensive necrosis with tumor cells present.
- •Subject is willing to have a fresh biopsy at least 3 days prior to neoadjuvant therapy if archival tissue is unavailable. Also willing to have a biopsy at the time of SOC surgery, if applicable.
- •Must have BRAF V600E mutation-negative tumor, as determined by BRAF V600E immunohistochemistry on tumor tissue or genetic/molecular testing of the tumor.
排除标准
- •Pregnant or breastfeeding (Note: breast milk cannot be stored for future use while the mother is being treated on the study). Females should not breastfeed while receiving study treatment and for 1 month from the last dose of XL
- •Patients who have had prior exposure to any immune modulating agents or any type of small molecule kinase inhibitor (including investigational agents) and have documented disease progression on these agents will not be eligible.
- •Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments (i.e., with use of disease modifying agents, corticosteroids (>10 mg of prednisone or equivalent) or immunosuppressive drugs) which may suggest risk of immune-mediated Adverse Events.
- •Replacement therapy (e.g.: thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment.
- •Subject history of documented allergic reactions or acute hypersensitivity reactions attributed to antibody treatments.
- •Subject is receiving prohibited medications or treatments as listed in the protocol that cannot be discontinued/replaced by an alternative therapy within 7 days of initiating treatment.
- •Participation in another clinical study with an investigational product during the last 3 weeks.
研究组 & 干预措施
neoadjuvant XL092 and cemiplimab
Subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their standard of care will receive neoadjuvant XL092 and cemiplimab. Adjuvant therapy may be indicated based on surgical pathology.
干预措施: Cemiplimab (Biological)
neoadjuvant XL092 and cemiplimab
Subjects with BRAFV600E wild type (WT) anaplastic thyroid cancer (ATC) who are scheduled to undergo surgical resection as part of their standard of care will receive neoadjuvant XL092 and cemiplimab. Adjuvant therapy may be indicated based on surgical pathology.
干预措施: XL092 (Drug)
结局指标
主要结局
Complete gross resection
时间窗: 12 weeks
Complete gross resection (CGR) is defined as the proportion of patients who undergo successful thyroidectomy with negative (R0) or microscopically positive (R1) surgical margins.
Non-hematologic treatment related adverse events (TRAEs)
时间窗: Up to 2 years
Non-hematologic treatment related adverse events (TRAEs) with neoadjuvant and maintenance XL092 and cemiplimab will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI- CTCAE) v5.0.
次要结局
- Overall survival (OS)(Up to 5 years)
- Objective response rate (ORR)(10 weeks)
- Time to surgery(12 weeks)
- The rate of pathologic response(12 weeks)
- Conversion rate from unresectable to resectable disease(12 weeks)
- Event free survival (EFS)(Up to 5 years)