An Open Label, Phase 1/2 Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 77
- 试验地点
- 14
- 主要终点
- Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1.
研究概览
简要总结
This is a Phase 1/2 study of HST-1011, a CBL-B inhibitor, being developed for the treatment of patients with advanced solid tumors, who relapsed while on or are refractory to approved anti-PD(L)1 therapies or other standard of care.
详细描述
This is a Phase 1/2 study of HST-1011, a CBL-B inhibitor, being developed for the treatment of patients with advanced solid tumors, who relapsed while on or are refractory to approved anti-PD(L)1 therapies or other standard of care.
In Phase 1 patients will receive HST-1011 as either monotherapy (Parts A1 and A2) or in combination with the anti-PD1 antibody, cemiplimab (Part B1 and B2).
Part A1 is a monotherapy dose escalation in which cohorts of patients will receive increasing doses of HST-1011. Upon completion of Part A1 dose escalation, an HST-1011 monotherapy dose optimization will commence (Part A2).
Part B1 is a dose escalation of HST-1011 given in combination with the standard dose/regimen of cemiplimab. Dosing in Part B1 may commence prior to the completion of Part A1. Upon completion of Part B1 dose escalation, an HST-1011 dose optimization in combination with cemiplimab will commence (Part B2).
Phase 2 will evaluate the preliminary antitumor activity of HST-1011 in combination with anti-PD(L)1 antibody or other standard of care therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Patient is at least 18 years of age.
- •Patient is capable of understanding and complying with protocol requirements.
- •Patient has signed and dated ICF.
- •Patient has a histologically confirmed, advanced solid tumor (metastatic, recurrent, and/or unresectable) in one of the following categories: 1) anti-PD-(L)1 relapsed/refractory; 2) platinum-resistant ovarian cancer; 4) anal cancer; 5) rectal cancer; or 6) castration-resistant prostate cancer
- •Patient has failed prior standard of care therapies appropriate for their metastatic disease.
- •Patient has at least 1 measurable non-central nervous system (CNS) lesions per RECIST 1.
- •Patient has provided consent for pre- and on-treatment biopsies.
- •Eastern Cooperative Performance Status of 0 or
排除标准
- •Patient has active autoimmune disease or other medical conditions requiring chronic systemic steroid therapy at the time of screening.
- •Patient has an unacceptable intolerance to anti-PD-(L)1 monoclonal antibody (Part B Only).
- •Patient has previously participated in a clinical study evaluating a CBL-B inhibitor.
- •Patients has untreated and/or symptomatic metastatic CNS disease.
- •Patient is currently taking any concomitant medications at Screening that have the potential to cause a clinically relevant drug-drug interaction with HST-
- •Patients with a history of gastrointestinal disease that may affect absorption of the study drug, or patients who are not able to take oral medications.
- •Patient has an active infection requiring systemic therapy.
- •Patient has known or suspected infection with SARS-CoV-2 virus.
研究组 & 干预措施
HST-1011 Monotherapy Dose Escalation (Part A1)
Multiple dose levels of HST-1011 to be evaluated.
干预措施: HST-1011 (Drug)
HST-1011 Monotherapy Dose Optimization (Part A2)
Evaluation of HST-1011 monotherapy dose/dose regimen.
干预措施: HST-1011 (Drug)
HST-1011 Dose Escalation in Combination with cemiplimab (Part B1)
Multiple dose levels of HST-1011 to be evaluated in combination with cemiplimab.
干预措施: HST-1011 (Drug)
HST-1011 Dose Escalation in Combination with cemiplimab (Part B1)
Multiple dose levels of HST-1011 to be evaluated in combination with cemiplimab.
干预措施: Cemiplimab (Biological)
HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2)
Evaluation of HST-1011 in combination with cemiplimab.
干预措施: HST-1011 (Drug)
HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2)
Evaluation of HST-1011 in combination with cemiplimab.
干预措施: Cemiplimab (Biological)
结局指标
主要结局
Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1.
时间窗: 12 months
Number of participants with DLTs, with Adverse Events (TEAEs, SAEs), with abnormal clinically significant vital signs, Electrocardiograms (ECGs), with abnormal physical examination findings, and abnormal laboratory test results.
To determine the Recommended Phase 2 Dose (RP2D) and schedule of HST-1011 monotherapy in Part A2 and in combination with cemiplimab in Part B2.
时间窗: 12 months
Integration of safety, PD, PK, and preliminary efficacy endpoints.
次要结局
- Evaluate the safety and tolerability of single-agent HST-1011 in Part A2.(12 months)
- Measurement of plasma concentrations of HST-1011 after monotherapy in Part A1 and Part A2 or in combination with cemiplimab in Part B to derive summary pharmacokinetic (PK) parameters including Tmax, Cmax, AUC0-last, Ctrough.(12 months)
- Characterize the concentration of peripheral blood cytokines/chemokines following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1.(12 months)
- Characterize global gene expression profiles following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2.(12 months)
- Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2.(12 months)
- Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2.(12 months)
- Duration of response (DOR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.(12 months)
- Disease Control Rate (DCR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.(12 months)
- Progression Free Survival (PFS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.(12 months)
- Overall Survival (OS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B.(12 months)