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
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.
Disease Group: Melanoma
Treatment Agent: APX005M ,Pembrolizumab
Treatment Location: Only at MDACC
Primary Objectives · To assess safety and tolerability of intratumoral APX005M given with systemic pembrolizumab and identify of the maximum tolerated dose/recommended phase 2 dose (MTD/RP2D) of the combination therapy in patients with metastatic melanoma (dose escalation phase). · To assess overall response rate (ORR) at 12 weeks after intratumoral injection of APX005M in combination with systemic pembrolizumab (dose expansion phase) (by using RECIST 1.1 criteria). Secondary Objectives · To evaluate the immunological impact of IT APX005M given with systemic pembrolizumab by quantifying the tumor infiltrated CD8+T-cells (pre/post-therapy) both in injected and non-injected tumors · To assess the overall safety and tolerability of IT APX005M given with systemic pembrolizumab in patients with metastatic melanoma (expansion phase). · To evaluate anti-tumor immune responses and clinical efficacy of intratumoral injection of IT APX005M with systemic Pembrolizumab (dose escalation phase) Exploratory Objectives · To explore potential associations between biomarker measures and anti-tumor activity · To assess overall survival at 1 year and 2 years following the start of therapy
IRB Review and Approval Date: 06/02/2017
Recruitment Status: Open
Projected Accrual: N/A
1) Be willing and able to provide written informed consent/assent for
2) Histologically or cytologically confirmed malignant melanoma from skin, or mucosal melanoma (i.e. ocular melanoma subjects are not eligible)
3) Measurable, unresectable stage III (in transit lesions) or stage IVA, IVB, IVC disease
4) 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
5) Age >/= 18 years
6) ECOG performance status 0 or 1
7) 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.
8) Platelet count greater than or equal to 100,000/mm^3
9) WBC >3000/mm^3
10) ANC>= 1500/mm^3
11) Hemoglobin >9 g/dL
12) Serum ALT and AST <3 the upper limit of normal (ULN); <5 ULN if there is liver involvement secondary to the tumor
13) Serum creatinine </= 2.0 mg/dl
14) Seronegative for HIV antibody
15) 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).
16) 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.
1) 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.
2) Active autoimmune disease requiring disease-modifying therapy.
3) Concurrent systemic steroid therapy higher than physiologic dose (>7.5 mg/day of prednisone or equivalent).
4) Any form of active primary or secondary immunodeficiency.
5) Patients with history of hematologic malignancy.
6) Active coagulopathy.
7) History of New York Heart Association class 3-4 congestive heart failure or history myocardial infarction within 6 months of starting study treatment.
8) History of arterial thrombosis within 3 months of starting study treatment.
9) History of clinically manifested CNS metastases, except if brain metastases have been treated, are stable and are asymptomatic
10) 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.
11) Subjects who have received prior immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1), anti-CD40.
12) Subjects that have received experimental vaccines or other immune therapies should be discussed with the Principal Investigator to confirm eligibility.
13) Active known clinically serious infections (> Grade 2 NCI-CTCAE version 4.03).
14) 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.
15) Women of child-bearing potential (WOCBP), women who are pregnant, or women who are nursing.
Information and next steps
Phase I/Phase II
Melanoma Medical Oncology
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