Phase I/II Dose Escalation and Cohort Expansion of Safety and Tolerability Study of Intratumoral CD40 Agonistic Monoclonal Antibody APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 34
- 试验地点
- 1
- 主要终点
- Safety and Tolerability
研究概览
简要总结
You are being asked to take part in this study because you have metastatic (cancer that has spread) melanoma.
The goal of Part 1 of this clinical research study is to find the highest tolerable dose of APX005M that can be given with pembrolizumab that can be given to patients with metastatic melanoma.
The goal of Part 2 of this study is to learn if the combination can help to control metastatic melanoma.
The safety of this drug combination will also be studied.
This is an investigational study. APX005M is not FDA approved or commercially available. It is currently being used for research purposes only. Pembrolizumab is FDA approved and commercially available for the treatment of metastatic melanoma. The combination of these drugs to treat metastatic melanoma is investigational.
The study doctor can explain how the study drug is designed to work.
Up to 41 participants will be treated in this study. All will take part at MD Anderson.
详细描述
Study Groups:
If you are found to be eligible to take part in this study, you will be assigned to a study group based on when you join this study. Up to 4 groups of 3 participants will be enrolled in Part 1, and up to 20 participants will be enrolled in Part 2.
If you are enrolled in Part 1, the dose of APX005M you receive will depend on when you join this study. The first group of participants will receive the lowest dose level of APX005M. Each new group will receive a higher dose of APX005M than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of APX005M is found.
If you are enrolled in Part 2, you will receive APX005M at the highest dose that was tolerated in Phase 1
All participants will receive the same dose level of pembrolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Be willing and able to provide written informed consent/assent for the trial.
- •Histologically or cytologically confirmed malignant melanoma from skin, or mucosal melanoma (i.e. ocular melanoma subjects are not eligible)
- •Measurable, unresectable stage III (in transit lesions) or stage IVA, IVB, IVC disease
- •At least two injectable lesions (amenable for direct injection or through the use of image guidance such ultrasound [US], CT or MRI) defined as any injectable cutaneous, subcutaneous, nodal, or visceral melanoma lesion ≥ 10 mm in longest diameter
- •Age ≥ 18 years
- •ECOG performance status 0 or 1
- •Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl.
- •Platelet count greater than or equal to 100,000/mm^3
- •WBC >3000/mm^3
- •ANC > 1500/mm^3
- •Hemoglobin >9 g/dL
- •Serum ALT and AST <3 the upper limit of normal (ULN); <5 ULN if there is liver involvement secondary to the tumor
- •Serum creatinine < 2.0 mg/dl
- •Seronegative for HIV antibody
- •Patients with a negative pregnancy test (urine or serum) must be documented within 14 days of screening for women of childbearing potential (WOCBP). A WOCBP has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 12 consecutive months (i.e. who has not had menses at any time in the preceding 12 consecutive months). Unless surgically sterile by bilateral tubal ligation or vasectomy of partner(s), the patient agrees to continue to use a barrier method of contraception throughout the study and for 4 months after the last dose of APX005M or Pembrolizumab such as: condom, diaphragm, hormonal, IUD, or sponge plus spermicide. Abstinence is an acceptable form of birth control.
排除标准
- •Patients who have previously received pembrolizumab or PD-/L1 blockade therapy. Adjuvant IFN-a, is allowed if last dose was received at least 6 months of starting study treatment.
- •Active autoimmune disease requiring disease-modifying therapy.
- •Concurrent systemic steroid therapy higher than physiologic dose (>7.5 mg/day of prednisone or equivalent).
- •Any form of active primary or secondary immunodeficiency.
- •History of hematologic malignancy.
- •Active coagulopathy.
- •History of New York Heart Association class 3-4 congestive heart failure or history myocardial infarction within 6 months of starting study treatment.
- •History of arterial thrombosis within 3 months of starting study treatment.
- •Patients with known symptomatic brain metastases requiring systematic corticosteroids. Patients with previous diagnosed brain metastases are eligible if they have completed their treatment and have recovered from acute effects of radiation therapy or surgery prior to the start of study medication, have discontinued corticosteroid treatment for their metastases for at least 2 weeks and are neurologically stable. Mild neurological deficits are allowed, if they do not interfere with the ability to judge the safety profile of APX005M.
- •Prior malignancy except the following: adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- •Subjects who have received prior immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1), anti-CD
- •Subjects that have received experimental vaccines or other immune therapies should be discussed with the Principal Investigator to confirm eligibility.
- •Active known clinically serious infections (> Grade 2 NCI-CTCAE version 4.03).
- •Prior systemic therapy, radiation therapy, or surgery within the 28 days of starting study treatment. Palliative radiotherapy to a limited field or palliative cryoablation is allowed after consultation with the Principal Investigator, at any time during the study participation including screening.
- •Women of child-bearing potential (WOCBP), women who are pregnant, or women who are nursing.
- •Known or underlying medical condition that, in the opinion of the investigator or sponsor, could make the administration of study drug hazardous to the subjects, or could adversely affect the ability of the subject to comply with or tolerate study procedures and/or study therapy, or confound the ability to interpret the tolerability of combined administration of APX005M and Pembrolizumab in treated subjects.
- •Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- •Has received a TB skin test within 14 days before the first dose of study drug.
- •Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient an inappropriate candidate for the study.
研究组 & 干预措施
APX005M + Pembrolizumab
Dose Escalation Phase:
Starting dose level of APX005M is 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses. Tumor site chosen based on volume to be injected.
All participants receive Pembrolizumab at 2 mg/kg by vein 1 time every 3 weeks (Weeks 0, 3, 6, 9, and 12). First dose of Pembrolizumab given 1-2 days before or after first dose of APX005M.
Dose Expansion Phase:
Starting dose level of APX005M is maximum tolerated dose from Dose Escalation Phase.
Participants receive same dosage of Pembrolizumab as in Dose Escalation Phase.
干预措施: APX005M (Drug)
APX005M + Pembrolizumab
Dose Escalation Phase:
Starting dose level of APX005M is 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses. Tumor site chosen based on volume to be injected.
All participants receive Pembrolizumab at 2 mg/kg by vein 1 time every 3 weeks (Weeks 0, 3, 6, 9, and 12). First dose of Pembrolizumab given 1-2 days before or after first dose of APX005M.
Dose Expansion Phase:
Starting dose level of APX005M is maximum tolerated dose from Dose Escalation Phase.
Participants receive same dosage of Pembrolizumab as in Dose Escalation Phase.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: Baseline to 2 years
To assess safety and tolerability of intratumoral APX005M given with systemic pembrolizumab and identify of the maximum tolerated dose/recommended phase 2 dose (MTD/PR2D) of the combination therapy in patients with metastatic melanoma.
Overall Response Rate (ORR)
时间窗: Baseline to 2 years
To assess best overall response after ibtratumoral injection of APX005M in combination with systemic pembrolizumab
次要结局
- Evaluation of Intratumoral CD8⁺ T Cells(Baseline to week 6)
- Overall Safety and Tolerability(Baseline to 2 years)
- Anti-tumor Immune Responses and Clinical Efficacy(Baseline to 2 years)