Dendritic Cell Therapy With Pembrolizumab for Metastatic or Unresectable Melanoma

NCT03325101 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: MC1771NCI-2017-0196717-001666
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib/II trial studies how well dendritic cell therapy after cryosurgery in combination with pembrolizumab works in treating patients with stage III-IV melanoma that cannot be removed by surgery. Vaccines made from a person's white blood cells mixed with tumor proteins may help the body build an effective immune response to kill tumor cells. Cryosurgery, also known as cryoablation or cryotherapy, kills tumor cells by freezing them. Monoclonal antibodies, such as pembrolizumab, may block tumor growth in different ways by targeting certain cells. Giving dendritic cell therapy after cryosurgery in combination with pembrolizumab may work better in treating patients with melanoma.

Conditions

Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Developed a DLT During the First 3 Cycles of Treatment.

  The primary outcome of the Phase I portion of this trial was to establish the tolerability of the proposed treatment schedule in order to move it forward into the Phase II portion of the trial. A maximum of 6 patients was to be enrolled onto the Schedule 1. If at most one of these 6 patients developed a DLT during the first 3 treatment cycles, then Schedule #1 would be carried forward to the Phase II portion of the trial. If not, then an additional 6 patients would be treated with a modified Schedule 1 where Pembrolizumab was eliminated from cycles 2 \& 3. Dose-limiting toxicity (DLT) were defined as the following possibly, probably, or definitely related AEs to protocol therapy during first 3 treatment cycles: Grade 3+ infusion reactions, acute kidney injury, chronic kidney disease, pneumonitis; or Grade 2 infusion reactions, acute kidney injury, chronic kidney disease or pneumonitis that does not resolve to Grade 0-1 within 21 days.

  Up to 3 months (3 cycles of 21 days and an additional 7 days for Cycle 1)

Secondary Outcomes (2)

• Incidence of Adverse Events

  30 months (through study completion)

• Overall Survival

  30 months (through study completion)

Other Outcomes (1)

• Progression-free Survival Time

  30 months (through study completion)

Study Arms (3)

Phase I Schedule 1

EXPERIMENTAL

Phase I Schedule 1: Cycle length is 21 days with the exception of cycle 1 which may be extended an additional 7 days to allow for dendritic cell production. Cycle 1 Day 1: Patients undergo apheresis over 4 hours and pembrolizumab IV over 30 minutes. Cycle 2 \& Cycle 3 Day 1: Pembrolizumab 200 mg is administered by IV over 30 minutes. Cycle 2 \& Cycle 3 either Day 1 or Day 2 (within 36 hours of receiving pembrolizumab): patients undergo cryosurgery (injection of 30-60 x 10\^6 mDCs and an injection of 0.5 ml Prenar13 such that two distinct metastatic lesions are cryoablated, one during cycle 2 and the other during cycle 3. Cycle 4 Day 1 and all subsequent cycles for a maximum of 2 years: Pembrolizumab 200 mg is administered by IV over 30 minutes

Procedure: Cryosurgery; Biological: Pembrolizumab; Procedure: Pheresis; Biological: Therapeutic Autologous Dendritic Cells

Phase I Schedule -1

EXPERIMENTAL

Phase I Schedule -1: Cycle length is 21 days with the exception of cycle 1 which may be extended an additional 7 days to allow for dendritic cell production. Cycle 1 Day 1: Patients undergo apheresis over 4 hours and pembrolizumab IV over 30 minutes. Cycle 2 \& Cycle 3 either Day 1 or Day 2 (within 36 hours of receiving pembrolizumab): patients undergo cryosurgery (injection of 30-60 x 10\^6 mDCs and an injection of 0.5 ml Prenar13 such that two distinct metastatic lesions are cryoablated, one during cycle 2 and the other during cycle 3. Cycle 4 Day 1 and all subsequent cycles for a maximum of 2 years: Pembrolizumab 200 mg is administered by IV over 30 minutes

Procedure: Cryosurgery; Biological: Pembrolizumab; Procedure: Pheresis; Biological: Therapeutic Autologous Dendritic Cells

Phase II Schedule

EXPERIMENTAL

Regimen depends upon the results of the Phase I portion of the study.

Procedure: Cryosurgery; Biological: Pembrolizumab; Procedure: Pheresis; Biological: Therapeutic Autologous Dendritic Cells

Interventions

Cryosurgery PROCEDURE

Undergo cryosurgery

Also known as: cryoablation, cryosurgical ablation

Phase I Schedule -1; Phase I Schedule 1; Phase II Schedule

Pembrolizumab BIOLOGICAL

IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Phase I Schedule -1; Phase I Schedule 1; Phase II Schedule

Pheresis PROCEDURE

apheresis

Also known as: Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Phase I Schedule -1; Phase I Schedule 1; Phase II Schedule

Therapeutic Autologous Dendritic Cells BIOLOGICAL

Intra-tumoral injection

Phase I Schedule -1; Phase I Schedule 1; Phase II Schedule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to curative local therapy
• Documented progression of disease after initiation of therapy with OR lack of response to therapy with a PD-1- or PD-L1-targeting monoclonal antibody (pembrolizumab, nivolumab, etc) after at least 18 weeks; NOTE: This treatment could have been at any time prior to registration
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Minimum of 3 radiographically apparent lesions such that there is:
• Minimum of one lesion in areas that have not been previously irradiated that is considered measurable by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria AND
• Minimum of two lesions in areas that have not been previously irradiated that are determined by interventional radiology to be of a size and in a location that a single probe could ablate at least 75% of the lesion; Note: Hepatic lesions measuring =\< 3 cm may be treated, as determined by interventional radiology; Note: Brain metastases are not acceptable as lesions defining measurable disease, nor are they candidate lesions for cryoablation
• Adequate venous access for apheresis as assessed by apheresis team; NOTE: If a central venous catheter is required for apheresis, the patient is not eligible
• Absolute neutrophil count (ANC) \>= 1000/mm\^3 obtained =\< 14 days prior to registration
• Absolute lymphocyte count \>= 500/mm\^3 obtained =\< 14 days prior to registration
• Platelet count \>= 100,000/mm\^3 obtained =\< 14 days prior to registration
• Hemoglobin \>= 10 g/dL obtained =\< 14 days prior to registration
• Total bilirubin =\< 1.5 x upper limit of normal (ULN), unless due to Gilbert?s disease obtained =\< 14 days prior to registration
• Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x ULN obtained =\< 14 days prior to registration
• Creatinine =\< 1.5 x ULN or calculated creatinine clearance \>= 60 mL/min for subject with creatinine ? 1.5 x institutional ULN obtained =\< 14 days prior to registration
• Negative serum pregnancy test for persons of childbearing potential =\< 7 days prior to registration

You may not qualify if:

• Any of the following:
• Pregnant persons
• Nursing persons
• History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
• Active tuberculosis or active, non-infectious pneumonitis
• Evidence of interstitial lung disease
• Active infection requiring the use of systemic antibiotics
• Symptomatic congestive heart failure (New York Heart Association classification III or IV cardiovascular disease, myocardial infarction =\< 6 months prior to registration, unstable angina pectoris or cardiac arrhythmia =\< 3 months prior to registration, or cardiac arrhythmia
• Currently receiving or have received any other investigational agent considered as a treatment for the primary neoplasm =\< 21 days prior to registration
• History of other primary malignancy requiring systemic treatment =\< 3 years prior to registration; patients must not be receiving chemotherapy or immunotherapy for another cancer; patients must not have another active malignancy requiring active treatment; EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix
• Failure to recover from prior side effects of immune checkpoint inhibitor therapy to =\< grade 1; NOTE: Patients will not be excluded for adrenal insufficiency or hypothyroidism secondary to immunotherapy provided they are receiving hormonal replacement
• Major surgery =\< 4 weeks prior to registration
• Prior chemotherapy, targeted therapy, or radiation therapy =\< 2 weeks prior to registration or who has not recovered (i.e. to =\< grade 1 or baseline) from an adverse event due to the previously administered therapy
• History of hypersensitivity and anaphylactoid reactions to pneumococcal vaccine or any component of the formulation, including diphtheria toxoid
• Active autoimmune disease such as Crohn?s disease, rheumatoid arthritis, Sjogrens? disease, systemic lupus erythematosus, or similar conditions requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease/syndrome difficult to control in the past; EXCEPTIONS (the following are allowed):

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Links

• Mayo Clinic web site

MeSH Terms

Conditions

Melanoma

Interventions

Cryosurgery; pembrolizumab; Blood Component Removal

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Ablation Techniques; Surgical Procedures, Operative; Therapeutics

Limitations and Caveats

The trial was closed to enrollment during the Phase I portion of the trial due to poor enrollment.

Results Point of Contact

• Title: Matthew Block, MD, PhD
• Organization: Mayo Clinic

Block.Matthew@mayo.edu

507-266-7446

Study Officials

• Matthew S. Block, M.D., Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Group 1: Phase I Schedule 1 Group 2: Phase I Schedule -1 (if Phase 1 Schedule 1 not well tolerated) Group 3: Phase II Schedule base on the findings of the Phase I portion of the trial

Study Record Dates

• First Submitted: October 25, 2017
• First Posted: October 30, 2017
• Study Start: November 15, 2017
• Primary Completion: June 14, 2020
• Study Completion: June 14, 2020
• Last Updated: June 12, 2025
• Results First Posted: June 12, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Available for 10 years post study closure.

Locations

US (1)