A Phase1, First-in-Human, Open-Label, Dose Escalation and Expansion Study of CUE-101 Monotherapy in Second Line or CUE-101 Combination Therapy With Pembrolizumab in First Line Patients With HPV16+ Recurrent/Metastatic HNSCC
概览
- 阶段
- 1 期
- 干预措施
- CUE-101
- 疾病 / 适应症
- Head and Neck Cancer
- 发起方
- Cue Biopharma
- 入组人数
- 80
- 试验地点
- 17
- 主要终点
- Dose Limiting Toxicity
- 状态
- 已完成
- 最后更新
- 3个月前
概览
简要总结
This is a multi-center, open-label, phase 1 dose escalation and expansion study evaluating the safety, anti-tumor effect, and immunogenicity of CUE-101 as monotherapy treatment in second line or CUE-101 Combination Therapy with Pembrolizumab in first line patients with HPV16+ Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
详细描述
CUE-101 is a novel fusion protein designed to activate and expand a population of tumor specific T cells to eradicate human papilloma virus (HPV)-driven malignancies. HPV causes multiple tumor types including cervical, head and neck squamous cell carcinoma (HNSCC) and anal cancers. Initial testing of CUE-101 will be conducted in HPV16+ HNSCC patients. The primary objectives of the Part A\&B, first-in-human trial, are to assess the safety and tolerability of CUE-101 in subjects with recurrent/metastatic HNSCC in the second line setting and to determine the maximum tolerated dose or recommended Phase 2 dose based on markers of biological activity. Pharmacokinetics (PK), antitumor immune response, preliminary antitumor activity and the potential for immunogenicity will also be assessed. The goal of Part C\&D is to characterize the safety, tolerability, and biological effects of CUE-101 in combination with pembrolizumab in patients with recurrent/metastatic HNSCC in the first line setting. This will be an open-label multicenter phase I trial conducted in the U.S. involving approximately 85 patients.
研究者
入排标准
入选标准
- •Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease. Patients must also be willing and able to comply with study procedures, including the acquisition of specified research specimens
- •Age ≥18 years old
- •ECOG performance status of 0 or 1
- •Life expectancy ≥12 weeks
- •Measurable disease as per RECIST 1.1 and documented by CT and/or MRI. Cutaneous or subcutaneous lesions must be measurable by calipers. Note: Lesions to be used as measurable disease for the purpose of response assessment must either a) not reside in a field that has been subjected to prior radiotherapy, or b) have demonstrated clear evidence of radiographic progression since the completion of prior radiotherapy and prior to study enrollment
- •R/M HNSCC that has progressed following at least 1 prior systemic therapy. Patients must have received platinum-based chemotherapy and/or pembrolizumab in the first-line setting
- •Patient must have HLA A\*0201 genotype as determined by genomic testing performed at a central laboratory designated by the Sponsor.
- •Patient must have histologically and/or cytologically proven tumor(s) that are HPV16+ and express 16INK4A. Archival tissue or FFPE tissue from a biopsy and/or surgery must be available for HPV16 and p16INK4A testing on all patients enrolled. All tumors must test positive for both HPV16 using RNA ISH and p16INK4A expression in tumor cells using IHC analysis determined in a central laboratory designated by the Sponsor. All tumors must have histologically or cytologically confirmed diagnoses.
- •Laboratory Features
- •Acceptable laboratory parameters as follows:
排除标准
- •Patients with symptomatic CNS metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
- •Need for concurrent treatment for the CNS disease (eg, surgery, radiation, corticosteroids \>10 mg prednisone/day or equivalent);
- •Progression of CNS metastases on MRI or CT for at least 28 days after last day of prior therapy for the CNS metastases; and/or
- •Concurrent leptomeningeal disease or cord compression.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- •History of prior allogeneic bone marrow, stem-cell or solid organ transplantation
- •Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 2 weeks (or 4 weeks, for antibody drugs), prior to the initiation of study drug administration. Patients may be on an investigational or other anti-neoplastic therapy during the screening phase of the study.
- •Treatment with radiation therapy within 2 weeks prior to the initiation of study drug administration.
- •Treatment with corticosteroids (\>10 mg per day prednisone or equivalent) or other immune suppressive drugs within the 14 days prior to the initiation of study drug administration.
- •History of clinically significant cardiovascular disease including, but not limited to:
研究组 & 干预措施
CUE-101 dose escalation and expansion
Part A\&B: CUE-101 Monotherapy IV infusion Q3W Dose Escalation (Part A) and Expansion (Part B)
干预措施: CUE-101
Pembrolizumab and CUE-101
Part C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)
干预措施: CUE-101
Pembrolizumab and CUE-101
Part C\&D: CUE-101 Dose Escalation in Combination with KEYTRUDA® (pembrolizumab) for injection, for IV use 200 mg Q3W (Part C). Expansion of pembrolizumab plus CUE-101 at the combination RP2D (Part D)
干预措施: KEYTRUDA®, Pembrolizumab
结局指标
主要结局
Dose Limiting Toxicity
时间窗: 36 months
The number of subjects who have dose limiting toxicities (DLTs), defined as clinically significant or ≥ Grade 3 Common Terminology Criteria for Adverse Events (CTCAE) v5.0, changes in adverse events (AEs), safety laboratory tests, physical examinations, electrocardiograms (ECGs), or vital signs
Serum PK parameters for CUE-101
时间窗: 36 months
Terminal half-life of CUE-101
次要结局
- Overall response rate (ORR)(36 months)