A Randomized Phase II Study of Amivantamab (JNJ-61186372) and Hyaluronidase (rHuPH20) Versus Cetuximab in Immunocompromised Participants With Recurrent Inoperable or Metastatic Cutaneous Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 暂停
- 入组人数
- 86
- 试验地点
- 103
- 主要终点
- Incidence of toxicity of interest (cohort A)
研究概览
简要总结
This phase II trial compares the effect of amivantamab and hyaluronidase to cetuximab for the treatment of skin (cutaneous) squamous cell carcinoma that has come back after a period of improvement and has not spread to other parts of the body (locally recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Amivantamab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Hyaluronidase is an endoglycosidase. It helps to keep amivantamab in the body longer, so that the medications will have a greater effect. Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of cancer cells. This may help keep cancer cells from growing. Giving amivantamab and hyaluronidase may be as effective as cetuximab for the treatment of locally recurrent or metastatic cutaneous squamous cell carcinoma.
详细描述
PRIMARY OBJECTIVES:
I. To evaluate the safety and preliminary efficacy of amivantamab monotherapy in patients with locoregionally incurable or metastatic cutaneous squamous cell carcinoma and an active immunosuppressed condition. (Cohort A) II. To compare progression-free survival (PFS) of amivantamab monotherapy versus cetuximab monotherapy in patients with locoregionally incurable or metastatic cutaneous squamous cell carcinoma and an active immunosuppressed condition. (Cohort B)
SECONDARY OBJECTIVES:
I. To estimate the frequency and severity of toxicities in each cohort and treatment arm.
II. To estimate confirmed objective response rate (ORR) (ORR, confirmed complete and partial responses by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1) in each cohort and treatment arm.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Participants must have pathologically proven diagnosis of cutaneous squamous cell carcinoma based on pathology from original diagnosis or from a metastatic/recurrent lesion
- •Participants must have measurable or non-measurable disease per RECIST 1.1 and must have their disease assessed by CT or MRI of chest/abdomen/pelvis (with contrast unless contraindicated) within 28 days prior to registration for measurable disease or within 42 days prior to registration for non-measurable disease. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1). Any lesions assessed using a non-diagnostic positron emission tomography (PET)/CT of chest/abdomen/pelvis will be considered non-measurable lesions. Pleural effusions, ascites and laboratory parameters are not acceptable as the only evidence of disease. Participants whose only measurable disease is within a previous radiation therapy port must demonstrate clearly progressive disease (in the opinion of the treating investigator) prior to registration to be considered measurable
- •NOTE: All diseases must be assessed and documented on the baseline tumor assessment form
- •Participants with exclusively locally recurrent disease must have either a contraindication to surgical treatment of lesions (i.e., complete resection is not possible or not expected to be clinically beneficial or resection conferring significant cosmetic or functional concerns) or have refused surgical or radiation treatment
- •Participants must be immunocompromised, defined as below. For cases where there is a lack of clarity, it is highly recommended study teams reach out to Drs. Swiecicki and Geiger for discussion:
- •An diagnosis of either chronic lymphocytic leukemia (CLL), acute leukemia, myelodysplastic syndrome, polycythemia vera, or myelofibrosis regardless of whether actively receiving therapy OR
- •A diagnosis of lymphoma or multiple myeloma either on antineoplastic therapy, or within 6 months after therapy completion OR
- •Recipient of an organ transplant (excluding corneal transplants or lung transplants)
- •If a transplant patient, documentation from the patient's transplant physician confirming that the patient's allograft is stable. Documentation must be dated within 180 days of registration OR
- •Autoimmune disease under active treatment with an immunosuppressive medication (as defined below)
- •Autoimmune diseases include but are not limited to: systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, myasthenia gravis, Guillain-Barre syndrome, autoimmune hepatitis, scleroderma, primary biliary cirrhosis, pemphigus, and bullous pemphigoid
- •Vitiligo, psoriasis, type 1 diabetes mellitus, hypothyroidism, or resolved childhood asthma/atopy are not eligible diagnoses
- •Immunosuppressant medications include the following:
- •Tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab, etanercept, golimumab, and infliximab)
- •Interleukin inhibitors (anakinra, ustekinumab, secukinumab, sarilumab, siltuximab, sulfasalazine, tildrakizumab, tocilizumab, chloroquine, and hydroxychloroquine)
- •Janus kinase (JAK) inhibitors (baricitinib, filgotinib, and tofacitinib)
- •Calcineurin inhibitors (cyclosporine and tacrolimus)
- •Metabolic inhibitors (azathioprine, leflunomide, mercaptopurine, methotrexate)
- •mTOR (mammalian target of rapamycin) inhibitors (sirolimus [rapamycin], everolimus, and zotarolimus)
- •Inosine monophosphate dehydrogenase inhibitors (mycophenolate)
- •Phosphodiesterase inhibitors (apremilast)
- •B cell inhibitors (rituximab)
- •T cell inhibitors (abatacept)
- •Glucocorticoids
- •Active treatment is defined as current use of any one or more of the following:
- •Oral glucocorticoid therapy (Prednisone equivalent > 10 mg/day) for 30 days prior to registration
- •Oral or subcutaneous immunosuppressive therapy for 90 days or more prior to registration
- •Two or more doses of intravenous non corticosteroid immunosuppressant within 90 days prior to registration
- •Participants with treated brain metastases must show no evidence of progression on follow-up brain imaging after central nervous system (CNS)-directed therapy
- •Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease must not require immediate CNS specific treatment at the time of study registration or anticipated during the first cycle of therapy
- •Participants must not have had prior treatment with cetuximab or another EGFR inhibitor within the last 365 days
- •Participant must be ≥ 18 years old at the time of registration
- •Participants must have Zubrod Performance Status of 0-2
- •Participants must have a complete medical history and physical exam within 28 days prior to registration
- •Leukocytes ≥ 3 x 10^3/uL (within 14 days prior to registration)
- •Absolute neutrophil count ≥ 1.5 x 10^3/uL (within 14 days prior to registration)
- •Platelets ≥ 100 x 10^3/uL (within 14 days prior to registration)
- •Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) unless history of Gilbert's disease. Participants with history of Gilbert's disease must have total bilirubin ≤ 5 x institutional ULN (within 14 days prior to registration)
- •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 3 × institutional ULN with the exception of subjects with documented liver metastases: AST and/or ALT ≤ 5.0 x institutional ULN (within 14 days prior to registration)
- •Participants must have a measured OR calculated creatinine clearance ≥ 30 mL/min using the following Cockcroft-Gault Formula. This specimen must have been drawn and processed within 14 days prior to registration
- •Participants must not have an active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis
- •Participants must not have a history of lung transplantation
- •Participants must not have a history of pulmonary graft versus host disease (GVHD)
- •Participants must have adequate cardiac function. Participants with known history or current symptoms of cardiac disease, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better
- •Participants with a history human immunodeficiency virus (HIV)-infection must be on effective anti-retroviral therapy at registration and have undetectable viral load test on the most recent test results obtained within 6 months prior to registration
- •Participants with a history of chronic hepatitis B virus (HBV) infection must have undetectable HBV viral load while on suppressive therapy on the most recent test results obtained within 6 months prior to registration, if indicated
- •Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. Participants currently being treated for HCV infection must have undetectable HCV viral load test on the most recent test results obtained within 6 months prior to registration, if indicated
- •Participants must not have an uncontrolled illness, including but not limited to:
- •Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting study treatment])
- •Active bleeding diathesis
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排除标准
- 未提供
研究组 & 干预措施
Arm I (amivantamab and hyaluronidase)
Patients receive amivantamab and hyaluronidase SC over at least 5 minutes on days 1, 8, 15 and 22 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT scan and/or MRI throughout the study.
干预措施: Computed Tomography (Procedure)
Arm II (cetuximab)
Patients receive cetuximab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT and/or MRI throughout the study.
干预措施: Cetuximab (Biological)
Arm II (cetuximab)
Patients receive cetuximab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT and/or MRI throughout the study.
干预措施: Computed Tomography (Procedure)
Arm II (cetuximab)
Patients receive cetuximab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT and/or MRI throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm I (amivantamab and hyaluronidase)
Patients receive amivantamab and hyaluronidase SC over at least 5 minutes on days 1, 8, 15 and 22 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT scan and/or MRI throughout the study.
干预措施: Magnetic Resonance Imaging (Procedure)
Arm II (cetuximab)
Patients receive cetuximab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT and/or MRI throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (amivantamab and hyaluronidase)
Patients receive amivantamab and hyaluronidase SC over at least 5 minutes on days 1, 8, 15 and 22 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT scan and/or MRI throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (amivantamab and hyaluronidase)
Patients receive amivantamab and hyaluronidase SC over at least 5 minutes on days 1, 8, 15 and 22 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days for 24 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection on study and CT scan and/or MRI throughout the study.
干预措施: Amivantamab and Recombinant Human Hyaluronidase (Drug)
结局指标
主要结局
Incidence of toxicity of interest (cohort A)
时间窗: Up to completion of the first cycle (cycle length = 28 days)
Defined as grade 3 or 4 skin rash that does not recover within 14 days, grade 3 or 4 non-hematologic toxicity that does not recover within 7 days, grade 4 hematologic toxicity including febrile neutropenia or organ transplant failure (for transplant patients only).
Progression free survival (PFS) (cohort B)
时间窗: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, up to 3 years
次要结局
- Organ rejection(Up to 5 years)
- Overall survival (OS)(From date of registration to date of death due to any cause, up to 5 years)
- PFS(From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, up to 5 years)
- Time to next treatment(Up to 3 years)
- Time to progression(Up to 3 years)
- Duration of objective response(Up to 5 years)