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CD40 Agonistic Monoclonal Antibody APX005M and Pembrolizumab in Treating Patients with Stage III-IV Melanoma

Trial Status: Active

This phase I / II trial studies the side effects and best dose of CD40 agonistic monoclonal antibody APX005M when given together with pembrolizumab and to see how well it works in treating patients with stage III-IV melanoma. Immunotherapy with monoclonal antibodies, such as CD40 agonistic monoclonal antibody APX005M and pembrolizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Inclusion Criteria

  • 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 or IVC disease
  • At least 2 injectable lesions (amenable for direct injection or through the use of image guidance such ultrasound [US], computed tomography [CT] or magnetic resonance imaging [MRI]) defined as any injectable cutaneous, subcutaneous, nodal, or visceral melanoma lesion >= 10 mm in longest diameter
  • Eastern Cooperative Oncology Group (ECOG) 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
  • White blood cells (WBC) > 3000/mm^3
  • Absolute neutrophil count (ANC) > 1500/mm^3
  • Hemoglobin > 9 g/dL
  • Serum alanine transferase (ALT) and aspartate transaminase (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 human immunodeficiency virus (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, intrauterine device (IUD), or sponge plus spermicide; abstinence is an acceptable form of birth control

Exclusion Criteria

  • Patients who have previously received prior pembrolizumab or programmed cell death 1 ligand 1 (PD-/L1) blockade therapy; adjuvant interferon alpha (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
  • Patients with history of hematologic malignancy
  • Active coagulopathy
  • History of New York Heart Association class 3-4 congestive heart failure or patients with 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-programmed cell death protein 1 [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
  • Active known clinically serious infections (> grade 2 National Cancer Institute [NCI]- Common Terminology Criteria for Adverse Events [CTCAE] version 4.03)
  • Prior systemic therapy, radiation therapy, or surgery within the 28 days of starting study treatment; palliative radiotherapy to a limited filed 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–Guerin (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 tuberculin (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


M D Anderson Cancer Center
Status: ACTIVE
Contact: Adi Diab
Phone: 713-792-2921


I. To assess safety and tolerability of intratumoral sotigalimab (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)

II. To assess overall response rate (ORR) at 12 weeks after intratumoral injection of APX005M in combination with systemic pembrolizumab (by using Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria). (dose expansion phase)


I. To evaluate the immunological impact of intratumoral (IT) APX005M given with systemic pembrolizumab by quantifying the tumor infiltrated cluster of differentiation 8 (CD8)+ T-cells (pre/post-therapy) both in injected and non-injected tumors.

II. To assess the overall safety and tolerability of IT APX005M given with systemic pembrolizumab in patients with metastatic melanoma. (expansion phase)

III. To evaluate anti-tumor immune responses and clinical efficacy of intratumoral injection of IT APX005M with systemic pembrolizumab. (dose escalation phase)


I. To explore potential associations between biomarker measures and anti-tumor activity.

II. To assess overall survival at 1 year and 2 years following the start of therapy.

OUTLINE: This is a phase I, dose escalation study of CD40 agonistic monoclonal antibody APX005M followed by a phase II study.

Patients receive CD40 agonistic monoclonal antibody APX005M intratumorally (IT) on weeks 0, 3, 6, and 9 (total of 4 doses only) and pembrolizumab intravenously (IV) on weeks 0, 3, 6, 9, and every 21 days. Patients may continue to receive pembrolizumab for up to 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up within 2 weeks and every 8-12 weeks for 2 years.

Trial Phase Phase I/II

Trial Type Treatment

Lead Organization
M D Anderson Cancer Center

Principal Investigator
Adi Diab

  • Primary ID 2015-0654
  • Secondary IDs NCI-2016-00675
  • ID NCT02706353