An Open-label, Multicenter, Dose Escalation Phase 1b Study to Assess the Safety and Pharmacokinetics of Subcutaneous Delivery of Amivantamab, a Human Bispecific EGFR and cMet Antibody for the Treatment of Advanced Solid Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 158
- 试验地点
- 19
- 主要终点
- Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)
研究概览
简要总结
The purpose of this study is to assess the feasibility of subcutaneous (SC) administration of amivantamab based on safety and pharmacokinetics and determine a dose, dose regimen and formulation for amivantamab SC delivery.
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
- •Part 1 and Part 2: Participant must have histologically or cytologically confirmed solid malignancy that is metastatic or unresectable and which may derive benefit from epidermal growth factor receptor (EGFR) or mesenchymal-epidermal transition tyrosine kinase receptor/hepatocyte growth factor receptor (cMet) directed therapy. Eligible tumor types include non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), hepatocellular cancer (HCC), colorectal cancer (CRC), renal cell cancer (RCC), medullary thyroid cancer (MTC), gastroesophageal cancer (GEC), mesothelioma, breast cancer (BC) and ovarian cancer (OC). Participants must have either progressed after prior standard of care therapy for metastatic disease, be ineligible for, or have refused all other currently available therapeutic options. In cases where participants refuse currently available therapeutic options, this must be documented in the study records.
- •Participant must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) at Screening and a negative urine or serum pregnancy test within 24 hours before the first dose of study drug
- •A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study drug
- •A man who is sexually active with a woman of childbearing potential must agree to use a condom and his partner must also be practicing a highly effective method of contraception (that is, established use of oral, injected or implanted hormonal methods of contraception; placement of an Intrauterine device [IUD] or Intrauterine system [IUS])
排除标准
- •Participant has uncontrolled inter-current illness, including but not limited to poorly controlled hypertension or diabetes, ongoing or active systemic infection (that is, has discontinued all antibiotics for at least one week prior to first dose of study drug), diagnosed or suspected viral infection (except Human immunodeficiency virus [HIV] positive participants with 1 or more of the following: a) not receiving highly active antiretroviral therapy; b) a change in antiretroviral therapy within 6 months of the start of screening; c) cluster of differentiation 4 (CD4)+ T-cell count less than [<]350 per cubic millimeters [mm^3] at screening; d) an acquired immunodeficiency syndrome-defining opportunistic infection within 6 months of the start of screening), or psychiatric illness/social situation that would limit compliance with study requirements, including ability to self-care for anticipated toxicities [that is. rash or paronychia]. Participants with medical conditions requiring chronic continuous oxygen therapy are excluded
- •Participant has had prior chemotherapy, targeted cancer therapy, or treatment with an investigational anti-cancer agent within 2 weeks or 4 half-lives, whichever is longer, before the first administration of study drug; or participant has received prior immunotherapy within 6 weeks before the first administration of study drug. For agents with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less, (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade less than [<] 2 hypothyroidism stable on hormone replacement). Autoimmune toxicities from previous immunotherapy must be fully resolved to baseline levels
- •Participants with untreated brain metastases. Participants with locally treated metastases that are clinically stable and asymptomatic for at least 2 weeks and who are off or receiving low-dose corticosteroid treatment (<=10 milligrams [mg] prednisone or equivalent) for at least 2 weeks prior to study treatment are eligible
- •Participant has an active malignancy other than the disease under study requiring treatment
- •Participant has leptomeningeal disease
研究组 & 干预措施
Part 2: Ami-HC and Ami-HC-CF
Participants will receive SC infusion of newly developed high concentration amivantamab (Ami-HC) or SC injection of amivantamab co-formulated with rHuPH20 (Ami-HC-CF).
干预措施: Ami-HC (Drug)
Part 1: Ami-LC-MD and Ami-LC
Participants in cohort 1a will receive amivantamab admixed with rHuPH20 (Ami-LC-MD) subcutaneous (SC) infusion and participants in cohort 1b will receive amivantamab (Ami-LC) SC infusion.
干预措施: Ami-LC (Drug)
Part 2: Ami-HC and Ami-HC-CF
Participants will receive SC infusion of newly developed high concentration amivantamab (Ami-HC) or SC injection of amivantamab co-formulated with rHuPH20 (Ami-HC-CF).
干预措施: Ami-HC-CF (Drug)
Part 1: Ami-LC-MD and Ami-LC
Participants in cohort 1a will receive amivantamab admixed with rHuPH20 (Ami-LC-MD) subcutaneous (SC) infusion and participants in cohort 1b will receive amivantamab (Ami-LC) SC infusion.
干预措施: Ami-LC-MD (Drug)
结局指标
主要结局
Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)
时间窗: Up to Day 29
Ctrough is the observed amivantamab serum concentration immediately prior to the next drug administration.
Number of Participants with Adverse Event (AE)
时间窗: Up to 4 years 1 month
An adverse event is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the drug. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
Number of Participants with Dose Limiting Toxicity (DLT)
时间窗: Up to Day 28
Number of participants with DLT will be assessed.
Number of Participants with Clinical Laboratory Abnormalities
时间窗: Up to 4 years 1 month
Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.
Observed Amivantamab Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough)
时间窗: Up to Day 29
Ctrough is the observed amivantamab serum concentration immediately prior to the next drug administration.
Number of Participants with Adverse Event (AE)
时间窗: Up to 4 years 1 month
An adverse event is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the drug. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product.
Number of Participants with Dose Limiting Toxicity (DLT)
时间窗: Up to Day 28
Number of participants with DLT will be assessed.
Number of Participants with Clinical Laboratory Abnormalities
时间窗: Up to 4 years 1 month
Number of participants with clinical laboratory (hematology, clinical chemistry, and urinalysis) abnormalities will be assessed.
次要结局
- Part 2: Maximum Amivantamab Dosing Interval Between Time Zero to Steady State(Up to 4 years 1 month)
- Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies(Up to 4 years 1 month)
- Epidermal Growth Factor Receptor (EGFR) Concentrations(Up to 4 years 1 month)
- Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers(Up to 4 years 1 month)
- Overall Response Rate (ORR)(Up to 4 years 1 month)
- Number of Participants with Anti-amivantamab and Anti-rHuPH20 antibodies(Up to 4 years 1 month)
- Epidermal Growth Factor Receptor (EGFR) Concentrations(Up to 4 years 1 month)
- Mesenchymal-Epidermal Transition Tyrosine Kinase Receptor/Hepatocyte Growth Factor Receptor (cMET) Markers(Up to 4 years 1 month)
- Overall Response Rate (ORR)(Up to 4 years 1 month)
- Part 2: Maximum Amivantamab Dosing Interval Between Time Zero to Steady State(Up to 4 years 1 month)