计划状态
招聘阶段
第 1 阶段允许先接受免疫治疗
是CRC 指导的试验
是药物
Aldesleukin, Cyclophosphamide, Fludarabine标签
MSI-H/ MMRd、MSS/ MMRp评论
Clinical trial by NCI SB (Surgery Branch); principal investigator is Dr. Steven Rosenberg. The study uses adoptive cell transfer (ACT) therapy that involves isolating T-cell receptors (TCR) that recognize mutated cancer neoantigens, and admits patients with metastatic colorectal cancer with a KRAS G12V or G12D mutation.
Study design has been modified: a vaccine targeting KRAS has been added to the ACT therapy.
Patients will receive also GRT-C903/GRT-R904, a prime and boost adenoviral/mRNA vaccine targeting KRAS G12D and G12V shared mutations (Gritstone Bio) (intramuscular injection). First dose will be administered on the same day they receive the engineered cells transfer. During the follow-up visits (at 4, 8, and 12 weeks after the cell infusion), participants will receive two or three additional doses of the boost vaccine.
有用链接
https://pubmed.ncbi.nlm.nih.gov/38816232/ A shared neoantigen vaccine combined with immune checkpoint blockade for advanced metastatic solid tumors: phase 1 trial interim results| 地点 | 位置状态 |
|---|---|
| 美国 | |
|
美国国立卫生研究院临床中心 马里兰州贝塞斯达 20892 |
招聘 |
联系方式
纳入标准
* 纳入标准：
* Participants with an appropriate HLA match for available Surgery Branch KRAS TCRs with evaluable metastatic solid cancer (e.g., gastrointestinal, genitourinary, breast, ovarian, non-small cell lung cancer (NSCLC) and other solid cancers) with known KRAS G12V or G12D mutation.
* Confirmation of diagnosis of cancer by the NCI Laboratory of Pathology.
* Refractory to standard systemic therapy. Specifically:
* Participants with metastatic colorectal cancer must have received oxaliplatin and/or irinotecan.
* Participants with breast and ovarian cancer must have received at least two systemic treatments.
* 患有 NSCLC 的参试者必须接受过至少一种铂类化疗方案和至少一种 FDA 批准的靶向治疗（如适用）。
* Participants with other solid tumors must have received at least one prior line of systemic treatment or have declined standard treatment.
* Participants with three (3) or fewer brain metastases that are = 18 years and 1000/mm^3 without growth factor support
* WBC >= 2500/mm^3
* Platelet count (Bullet) 80,000/mm3
* Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.
* 化学：
* Serum ALT/AST <= 5.0 x ULN
* Serum creatinine <= 1.6 mg/dL
* Total bilirubin <= 2.0 mg/dL, except in participants with Gilbert s Syndrome, who must have a total bilirubin < 3.0 mg/dL.
* 参试者在报名时必须已完成之前的任何系统治疗。
NOTE: Participants may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less.
* For participants with NSCLC or lung metastases, more than two weeks must have elapsed since any prior palliation for major bronchial occlusion or bleeding at the time the patient receives the preparative regimen, and patient s toxicities must have recovered to a grade 1 or less.
* 受试者能够理解并愿意签署书面知情同意书。
* 愿意签署持久授权书。
* Participants must be co-enrolled on protocol 03-C-0277.
排除标准
排除标准：
* Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant.
* Any form of secondary immunosuppression.
* 需要抗感染治疗的活动性全身感染、凝血功能障碍或任何其他活动性或无补偿的重大疾病。
* For participants with NSCLC or lung metastases, any major bronchial occlusion or bleeding not amenable to palliation.
* 任何形式的原发性免疫缺陷（如严重联合免疫缺陷病和艾滋病）。
* 有主要器官自身免疫疾病史。
* 并发机会性感染（本方案中评估的实验性治疗依赖于完整的免疫系统。免疫能力下降的参与者可能对试验性治疗的反应较差，更容易受到其毒性的影响）。
* History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, aldesleukin or vaccines.
* Clinically significant participant history which in the judgment of the Principal Investigator (PI) would compromise the participants ability to tolerate high-dose aldesleukin.
* 有冠状动脉血管重建史或缺血性症状。
* For select participants with a clinical history prompting cardiac evaluation: last known LVEF <= 45%.
* For select participants with a clinical history prompting pulmonary evaluation: known FEV1 <= 50% predicted.
