APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma

Prior treatment

• 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.
• Concurrent systemic steroid therapy higher than physiologic dose (>7.5 mg/day of prednisone or equivalent).
• 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.
• Subjects who have received prior immune checkpoint inhibitors (e.g., anti-PD-1, anti-PD-L1), anti-CD40.
• Subjects that have received experimental vaccines or other immune therapies should be discussed with the Principal Investigator to confirm eligibility.
• 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.
• 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 illness

• Active autoimmune disease requiring disease-modifying therapy.
• History of hematologic malignancy.
• 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.
• 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.
• Active known clinically serious infections (> Grade 2 NCI-CTCAE version 4.03).
• 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.

Lab values

• 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.

Other

• Any form of active primary or secondary immunodeficiency.
• Active coagulopathy.
• Women of child-bearing potential (WOCBP), women who are pregnant, or women who are nursing.

• 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.