A Phase Ib/II Study to Evaluate HMBD-001 in Combination With Cetuximab, With or Without Docetaxel in Participants With Advanced Squamous Cell Carcinomas
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 398
- 试验地点
- 30
- 主要终点
- Incidence and Nature of Adverse Events (AEs)
研究概览
简要总结
This is a Phase Ib/II multi-center, open-label study of HMBD-001 in combination with cetuximab with or without docetaxel in participants with advanced Squamous Cell Cancers
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Ability to understand and be willing to sign an informed consent form
- •Males and females aged over 18 years (or having reached the age of majority according to local laws if the age of majority is > 18 years of age)
- •Eastern Cooperative Oncology Group (ECOG) status of 0 to 1
- •Arm B only: Locally advanced or metastatic squamous non-small cell lung cancer for which all available standard of care treatment options have been exhausted or refused and for which at least one lesion is measurable
- •Arm C only: Advanced or metastatic sqNSCLC, HNSCC, ESCC, CSCC, cervical SCC, NPC and other SCCs with at least one prior line of systemic therapy,
- •Have an estimated life expectancy of at least 3 months
- •Participants must be willing to provide a fresh tumor biopsy sample
- •Have adequate organ function
- •Females must be non-pregnant and non-lactating, willing to use a highly effective method of contraception from screening until study completion or be either surgically sterile or post-menopausal
- •Males must be surgically sterile, abstinent, or if engaged in sexual relations with a woman of child-bearing potential, the participant and his partner must be surgically sterile or using an acceptable, highly effective contraceptive method from screening until study completion
排除标准
- •Prior treatment with HMBD-001, docetaxel, cetuximab or any other agent that targets Epidermal Growth Factor Receptor (EGFR) or HER3, including pan-HER inhibitors. Prior treatment with docetaxel is allowed for Arm C
- •Receipt of prior targeted therapy, including but not limited to those targeting EGFR activating mutations, ALK fusions, ROS rearrangements, RET fusions or mutations, BRAF V600E mutation, MET exon 14 skipping mutation, and/or KRAS G12C mutation
- •Persistent clinically significant toxicities (Grade ≥2) from previous anti-cancer therapy except for Grade >2 toxicities that are considered unlikely to put the participant at an increased risk of treatment-related toxicity and/or impact the study results e.g., alopecia
- •Most recent anti-cancer therapy including radiotherapy at least 4 weeks, or nitrosourea or mitomycin 3 at least 6 weeks, or 5 half-lives whichever is shorter prior to starting the assigned study treatment
- •Symptomatic primary Central Nervous System (CNS) cancer or metastases unless the symptoms are stable for at least 28 days prior to the first dose of the study drug and any symptoms have returned to baseline
- •Evidence of abnormal cardiac function
- •History of uncontrolled allergic reactions and/or known expected hypersensitivity to the study drugs used in the treatment arm to which the participant is to be enrolled into
- •Any other known active malignancy except for treated cervical intraepithelial neoplasia, or non-melanoma skin cancer
- •Any uncontrolled illness or significant uncontrolled condition(s) requiring systemic treatment
- •Known Human Immunodeficiency Virus (HIV) infection
- •Active hepatitis B or hepatitis C infection
- •Pregnant or breast feeding
- •COVID 19 infection within 3 months prior to the first dose of the study drug
- •COVID 19 vaccination within 14 days prior to the first dose of the study drug
- •Treatment with strong inhibitors or inducers of CYP3A4
研究组 & 干预措施
Arm A
Participants receive HMBD-001 with docetaxel. This treatment arm is closed to recruitment.
干预措施: Docetaxel (Drug)
Arm B
Participants receive HMBD-001 with docetaxel plus cetuximab. This treatment arm is closed to recruitment.
干预措施: Docetaxel (Drug)
Arm B
Participants receive HMBD-001 with docetaxel plus cetuximab. This treatment arm is closed to recruitment.
干预措施: Cetuximab (Drug)
Arm A
Participants receive HMBD-001 with docetaxel. This treatment arm is closed to recruitment.
干预措施: HMBD-001 (Drug)
Arm C
Participants receive HMBD-001 with cetuximab
干预措施: HMBD-001 (Drug)
Arm B
Participants receive HMBD-001 with docetaxel plus cetuximab. This treatment arm is closed to recruitment.
干预措施: HMBD-001 (Drug)
Arm C
Participants receive HMBD-001 with cetuximab
干预措施: Cetuximab (Drug)
结局指标
主要结局
Incidence and Nature of Adverse Events (AEs)
时间窗: From the time the Informed Consent Form (ICF) is signed until 30 days after last dose of study treatment
Incidence, nature and severity of adverse events (AEs) and serious adverse events (SAEs), changes in laboratory parameters, vital signs and ECG results per NCI CTCAE V5.0 Incidence of dose interruptions and modifications An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product temporally associated with the use of study treatment, whether or not considered to be related to the study treatment
Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1
时间窗: Up to 24 months
The ORR is defined as the proportion of subjects with confirmed Complete Response (CR) or confirmed Partial Response (PR), based on RECIST Version 1.1
Number of participants with dose-limiting toxicities (DLTs)
时间窗: During the first three weeks of study treatment
DLTs will be assessed in the dose escalation cohorts and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment
Number of participants with dose-limiting toxicities (DLTs) - applicable to part A
时间窗: From date of enrollment (first dosing) until the end of Cycle 1 (each cycle is 21 days)
DLTs will be assessed in the dose escalation cohorts and are defined as toxicities that meet pre-defined severity criteria and assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurs within the first cycle (3 weeks) of treatment
Six months progression-free survival (PFS) - applicable to part B
时间窗: From date of enrollment (first dosing) until disease progression or death, assessed up to 6 months
Number of participants achieving progression-free survival (PFS) at 6 months
次要结局
- Objective Response Rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) V1.1(From date of enrollment (first dosing) until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 48 months)
- HMBD-001 serum concentration-time profile and derived PK parameters(From date of enrollment (first dosing) until date of end of treatment from any cause, including multiple treatment cycles (each cycle is 21 days), assessed up to 48 months)
- HMBD-001 Immunogenicity Profile(From date of enrollment (first dosing) until date of end of treatment from any cause, including multiple treatment cycles (each cycle is 21 days), assessed up to 48 months)