NCT06021626招募中1 期
A Phase I Trial of CRD3874-SI, a STING Agonist, in Patients With Advanced/Metastatic Malignant Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 81
- 试验地点
- 14
- 主要终点
- maximum tolerated dose (MTD)
研究概览
简要总结
This study will test the safety of a study drug called CRD3874-SI. The researchers will test different doses of CRD3874-SI to find the highest dose that causes few or mild side effects in participants. After the researchers find the highest safe dose of CRD3874-SI, they will test that dose in new groups of participants to help them learn more about the side effects of the study drug and find out whether CRD3874-SI is an effective treatment for for patients with advanced or metastatic malignant solid tumors including sarcoma and Merkel Cell Carcinoma. (MCC), Head and neck squamous cell carcinoma (HNSCC), Adenoid cycstic carcinoma (ACC), Uveal Melanoma, Muscosal and Acral melanoma, and Non small cell lung cancer. The researchers will also look at how the body absorbs, distributes, and gets rid of CRD3874-SI, and the how the body and immune system respond to CRD3874-SI.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Male or female age ≥ 18 years at the time of informed consent.
- •Be capable, willing, and able to provide written informed consent.
- •Be willing to comply with clinical trial instructions and requirements, including tumor biopsies (if feasible and required per protocol).
- •Patients must have a locally advanced or metastatic cancer, a malignant solid tumor that has progressed on at least one line of systemic therapy or for which no standard treatment is available, the participant is intolerant to available treatment, or the participant declined standard of care systemic therapy.
- •In the dose escalation phase study patients with the following tumor types will be eligible: Of note patients who declined or were intolerable of standard of care systemic therapy will be considered in all dose expansion cohorts.
- •Head and neck squamous cell carcinoma (HNSCC)
- •Participants must have histologically or cytologically confirmed recurrent and/or metastatic HNSCC and must have received 1-2 prior lines of systemic anti-cancer therapy including a checkpoint inhibitor (patients treated initially with immune checkpoint blockade alone followed by the addition of other drugs in combination [i.e., cytotoxic chemotherapy or EGFR inhibitor], will be considered 1 line of therapy.
- •HPV positive (p16 IHC positive or HPV RNA ISH positive), PD-L1 CPS score high (≥1)
- •HPV negative (p16 IHC negative or HPV RNA ISH negative), PD-L1 CPS score high (≥1)
- •Adenoid cystic carcinoma (ACC)
- •Participants must have histologically or cytologically confirmed recurrent and/or metastatic ACC (cancers arising from non-salivery gland primary sites are eligible) and may have received none or up 2 prior lines of systemic anti-cancer therapy.
- •Merkel cell carcinoma (MCC)
- •Participants must have histologically or cytologically confirmed recurrent and or metastatic MCC and must have received at least one but no more than 3 prior lines of systemic anti-cancer therapy including a checkpoint inhibitor and may not have received prior chemotherapy for MCC.
- •Monotherapy alone
- •Radiation therapy
- •Patients will receive palliative radiation therapy to a tumor site if they have at least one other site of measureable disease that can be chosen as the target lesion to assess response to investigational therapy.
- •Sarcoma that has demonstrated clinical benefit or an objective response to immune checkpoint blockade or sarcoma subtypes that are considered immunogenic subtypes including but not limited to undifferentiated pleomorphic (UPS) or myxofibrosarcoma (MFS), angiosarcoma, alveolara soft part sarcoma, or undifferentiated sarcoma will be considered.
- •Uveal Melanoma
- •Participants must have histologically or cytologically confirmed recurrent and/or metastatic uveal melanoma and received at least one but no more than two prior lines of systemic anti-cancer therapy including tebentafusp (if HLA-A 02:01+, unless patient declined or was deemed ineligible) and/or immune checkpoint inhibitor. Melphalan PHP will count as a line of therapy if give on its own. Unlimited partial hepatic directed therapy will be permitted.
- •Mucosal and Acral melanoma
- •Participants must have histologically or cytologically confirmed recurrent and/or metastatic mucosal or acral melanoma and received at least one but no more than two prior lines of systemic anti-cancer therapy including prior exposure to immune checkpoint inhibition. Patients treated with BRAF-MEK therapy may have up to 3 prior lines of therapy.
- •Non small cell lung cancer
- •Participants must have histologically or cytologically confirmed locally advanced/metastatic non-small cell lung cancer with prior exposure to immune checkpoint inhibition and received at least one but no more than 2 prior lines of systemic anti-cancer therapy.
- •Participants must have histologically or cytologically confirmed locally advanced/metastatic sarcoma and must have received at least one but no more than 2 prior lines of systemic anti-cancer therapy. Patients will receive palliative radiation therapy to a tumor site if they have at least one other site of measureable disease that can be chosen as the target lesion to assess response to investigational therapy
- •Adequate performance status: ECOG 0 or 1/KPS 100-70%.
- •Life expectancy of at least three months after the first CRD3874 infusion, according to the Investigator's opinion
- •Presence of measurable disease per RECIST v1.1.Target lesion(s) must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment.
- •In the dose expansion phase , participants must agree to have a pretreatment tumor biopsy for research purposes. Participants in whom biopsy is technically not feasible or in whom the associated procedure would result in unacceptable risk, in the opinion of the Investigator, or patients who do not wish to have a biopsy, archival tissue (most recently procured sample where tissue is available) may be used instead, if available.
- •In the dose expansion phase , participants must agree to on-treatment tumor biopsy for research purposes. Participants in whom biopsy is technically not feasible or in whom would result in unacceptable risk, in the opinion of the Investigator, or patients who do not wish to have a biopsy- may be exempted from the biopsy requirement with discussion with the Principal Investigator .
- •Female subject of childbearing potential (defined as a sexually mature female who has not undergone a hysterectomy or bilateral oophorectomy or who has not been naturally postmenopausal for at least 24 consecutive months) should have a negative serum pregnancy testing at screening visit and within 72 hours prior to the first dose of study medication.
- •Adequate organ function determined within 14 days of treatment initiation, defined as follows:
- •Hemoglobin ≥ 9.0 g/dL
- •Absolute neutrophil count ≥ 1,000/mm^3 (1.0 x 10^9/L)
- •Platelet count ≥ 100,000/mm3 (100 x 10^9 /L)
- •Serum bilirubin ≤ 1.2x upper limit of normal (ULN) OR direct bilirubin ≤ ULN for participants with total bilirubin level > 1.2x ULN
- •Aspartate aminotransferase (AST) ≤ 2.5x ULN OR ≤ 5x ULN for participants with liver metastases
- •Alanine aminotransferase (ALT) ≤ 2.5x ULN OR ≤ 5x ULN for participants with liver metastases
- •Albumin ≥ 2.5mg/dL.
- •Calculated creatinine clearance (CrCl) ≥ 50 mL/min by Cockcroft-Gault formula or CKD-EPI 2021
- •International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5x ULN unless participant is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants.
- •Activated partial thromboplastin time (aPTT) ≤ 1.5x ULN unless participant is receiving anticoagulant therapy as long as PT and PTT is within therapeutic range of intended use of anticoagulants
- •Left ventricular ejection fraction (LVEF) > 50%, as measured by echocardiogram (2D-ECHO) or multi-gated acquisition scan (MUGA)
排除标准
- •* Known prior severe hypersensitivity to an investigational product or any component of the study drug therapy's formulations including polyethylene glycol (PEG), (NCI CTCAE v5.0 Grade ≥ 3)
- •* Evidence of clinically significant immunosuppression such as the following:
- •* Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease
- •* Concurrent opportunistic infection
- •* Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. In the setting of non-immune mediated indications for use, chronic/active low dose steroid (equivalent to \ 55 years with cessation of menses for 12 or more months or less than 55 years but with no spontaneous menses for at least two years or less than 55 years and spontaneous menses within the past one year but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy) and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels \> 40 IU/L) or postmenopausal estradiol levels (\< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved\] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy.)
- •* The presence of a concurrent active malignancy that in the opinion of the investigator could compromise the conduct of the study or interfere with determining the outcomes of the study objectives.
- •* History of non-infectious colitis.
研究组 & 干预措施
CRD3874-SI
Experimental
Phase 1a: starting dose of 0.1 mg/kg, Phase 1b: RP2D determined during Phase 1a. Cycle 1 & 2: once weekly infusion x 4 (Days 1, 8, 15, 22) over 28-day cycle. Cycle 3 onwards: weekly infusion x 3 (Days 1, 8, 15) over 28-day cycle From cycle 3 on wards if a patient is tolerating treatment well and agreeable to continue continuous weekly treatment this will be permitted. The dose expansion phase will explore CRD3874-SI at the RP2D and one additional clinically active dose levels in select solid tumor type. In the dose expansion phase, research blood tests for Peripheral blood mononuclear cells (PBMCs) will be performed before study drug administration on Day 1 of Cycles 1, 2 and 3 and the EOT visit (± 3 days).
干预措施: CRD3874 (Drug)
结局指标
主要结局
maximum tolerated dose (MTD)
时间窗: 1 year
The MTD is defined as the highest dose level studied at which \<2 subjects out of 6 experience a DLT. A dose level under consideration as the MTD will be expanded to six patients if only three have been accrued.
objective response rate (ORR) (Dose expansion)
时间窗: up to 48 weeks
by RECIST v1.1
次要结局
未报告次要终点
研究者
研究点 (14)
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