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APX005M in Combination With Systemic Pembrolizumab in Patients With Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02706353
Recruitment Status : Recruiting
First Posted : March 11, 2016
Last Update Posted : December 14, 2020
Apexigen, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: APX005M Drug: Pembrolizumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 2, 2017
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: 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.

Drug: APX005M

Dose Escalation Phase Starting Dose Level of APX005M: 0.1 mg injected directly into 1-3 tumors every 3 weeks (Weeks 0, 3, 6, and 9) for up to 4 doses.

Dose Expansion Phase Starting Dose Level of APX005M: Maximum tolerated dose from Dose Escalation Phase.

Drug: Pembrolizumab
Dose Escalation and Expansion Phase Dose of Pembrolizumab: 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.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Primary Outcome Measures :
  1. Maximum Tolerated Dose/Recommended Phase 2 Dose (MTD/RP2D) of APX005M in Combination with Pembrolizumab in Participants with Metastatic Melanoma - Dose Escalation Phase [ Time Frame: 3 weeks ]
    MTD defined as the highest dose for which the posterior probability of toxicity is closes to 30%, among all the tried doses i for which Pr (δ i > 0.30 | data) < 0.95. Toxicities graded according to the National Cancer Institute Common Terminology Criteria (CTC) for Adverse Events version 4.03.

  2. Overall Response Rate (ORR) After Intratumoral Injection of APX005M in Combination with Pembrolizumab in Participants with Metastatic Melanoma - Dose Expansion Phase [ Time Frame: 12 weeks ]
    Tumor response to therapy assessed using immune-related response criteria (irRC), which is a modified version of the World Health Organization (WHO) criteria.

Secondary Outcome Measures :
  1. Immune-Related Best Overall Response (irBOR) of APX005M in Combination with Pembrolizumab in Participants with Metastatic Melanoma [ Time Frame: 12 weeks ]

    irBOR is the best confirmed immune-related response criteria (irRC) overall response over the study as a whole, recorded between the date of first dose until the last tumor assessment.

    Correlation between change in cluster of differentiation 8 (CD8+) T-cell density of injected lesion and tumor shrinkage of non-injected lesion conducted based on Pearson's correlation coefficient and Spearman's rank correlation coefficient.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Be willing and able to provide written informed consent/assent for the trial.
  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.

Exclusion Criteria:

  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 from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02706353

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Contact: Adi Diab, MD 713-792-2921

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United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Clinical Research Operations   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Apexigen, Inc.
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Principal Investigator: Adi Diab, MD M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02706353    
Other Study ID Numbers: 2015-0654
NCI-2016-00675 ( Registry Identifier: NCI CTRP )
First Posted: March 11, 2016    Key Record Dates
Last Update Posted: December 14, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Metastatic Melanoma
Intratumoral APX005M
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antineoplastic Agents, Immunological
Antineoplastic Agents