Intratumoral Injection of Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Talimogene Laherparepvec (T-VEC)

NCT03747744 | Unknown Phase 1

• 1 other identifier: 2017-BN-002
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Over the past few years it has become evident that cancer cells can be recognized by the patient's own immune system. The immunological mechanisms at play are often referred to as the "cancer immune cycle" (Chen and Mellman 2013; Mellman 2013; Chen and Mellman 2017).In immune-evasive tumors a pivotal role has been attributed to myeloid dendritic cells (myDC) in regulating the activity of anti-tumor CTL activity within the TME (Broz, Binnewies et al. 2014). In animal models, myDC have been demonstrated to play an essential role in "licensing" anti-tumor CTLs to eradicate tumor cells. These myDC also migrate to tumor-draining lymph nodes and present tumor antigens to T-cells in these secondary lymphoid organs (Roberts, Broz et al. 2016). Human myDCs exist in two subsets that are differentiated by expression of either the BDCA-1 or BDCA-3 surface marker. The CD1c (BDCA-1)+ antigen is specifically expressed on human dendritic cells, which are CD11chighCD123low and represent the major subset of myDCs in human blood (about 0.6 % of all peripheral blood mononuclear cells (PBMCs)). CD1c (BDCA-1)+ myDC play an important role in the cross-presentation of tumor antigens following immunogenic cell death (Di Blasio, Wortel et al. 2016). Under conditions of tumor growth, myDC will be poorly recruited to the tumor microenvironment, do not get activated and thereby fail to efficiently coordinate anti-tumor immunity within the tumor micro-environment and present tumor associated antigens within tumor-draining lymph nodes. Talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus based on a modified herpes simplex virus (HSV) type 1 designed to selectively replicate in and lyse tumor cells while promoting regional and systemic antitumor immunity. In this phase I clinical trial we propose to investigate the safety of intratumoral injection of autologous CD1c (BDCA-1)+ myDC in non-visceral metastases of melanoma plus intratumoral injection of T-VEC (at its approved dose and regimen for the treatment of melanoma). We hypothesize that CD1c (BDCA-1)+ myDC in the T-VEC inflamed tumor microenvironment of the metastasis will capture tumor antigens in vivo and through cross-presentation of these antigens coordinate an effective anti-tumor T-cell response.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

  Safety of intratumoral injection with CD1c (BDCA-1)+ myDC and intratumoral injection of T-VEC

  through study completion, up to 1 year

Study Arms (1)

CD1c (BDCA-1)+ myDC

EXPERIMENTAL

CD1c (BDCA-1)+ myDC

Other: CD1c (BDCA-1)+ myDC

Interventions

CD1c (BDCA-1)+ myDC OTHER

Intratumoral injection in subcutaneous, cutaneous, soft tissue metastases

Also known as: intratumoral injection of talimogene laherparepvec (T-VEC)

CD1c (BDCA-1)+ myDC

Eligibility Criteria

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

You may qualify if:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
• Male or female age ≥ 18 years at the time of informed consent
• All subjects must have histologically confirmed advanced melanoma that cannot be completely surgically resected and have failed all standard curative and live prolonging therapy.
• All subjects must have non-visceral metastatic disease localizations that are amenable to intra-tumor injection by clinical and ultrasound (US) guidance. These metastases should be amenable to a safe post-injection biopsy (partial or complete).
• ECOG performance status of 0 or 1
• Candidate for intralesional therapy defined as either one of the following: a) at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion ≥ 10 mm in longest diameter, b) multiple injectable melanoma lesions that in aggregate have a longest diameter of ≥ 10 mm injectable disease
• Adequate organ function determined within 28 days prior to enrollment, defined as follows: a) Hematological, i) Absolute neutrophil count ≥ 1500/mm3 (1.5x109/L) ii) Platelet count: ≥ 75.000/mm3 (7.5x109/L) iii) Hemoglobin: ≥ 8 g/dL (without need for hematopoietic growth factor or transfusion support) b) Renal, i) Serum creatinine: 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels \> 1.5 x ULN. (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard). c) Hepatic, i) Serum bilirubin: 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 1.5 x ULN ii) Aspartate aminotransferase (AST): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases iii) Alanine aminotransferase (ALT): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases d) Coagulation, i) International normalization ratio (INR) or prothrombin time (PT): 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants ii) PTT or aPTT: 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of intended use of
• Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Subject has a tumor sample (archival sample obtained within 3 months prior to study participation or newly obtained biopsy). Subject must submit the tumor sample during screening. Subjects with a non-evaluable archival sample may obtain a new biopsy and subjects with a non-evaluable newly obtained biopsy may undergo re-biopsy at the discretion of the investigator.
• Adequate vascular access to undergo a leucapheresis.

You may not qualify if:

• Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \>10 mg/day of prednisone or equivalent. The exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability.
• History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia)
• History of other malignancy within the past 5 years with the following exceptions: i) Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for \> 5 years before enrollment and felt to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment iii) Adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment iv) Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment v) Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment vi) Adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment
• Prior therapy with T-VEC or any other oncolytic viruses
• Prior treatment of other tumor vaccine
• Receive live vaccine within 28 days prior to enrollment
• Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
• Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
• Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management
• Other investigational procedures while participating in this study are excluded.

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (1)

UZ Brussel

Brussels, 1090, Belgium

Location

Related Publications (1)

• Schwarze JK, Tijtgat J, Awada G, Cras L, Vasaturo A, Bagnall C, Forsyth R, Dufait I, Tuyaerts S, Van Riet I, Neyns B. Intratumoral administration of CD1c (BDCA-1)+ and CD141 (BDCA-3)+ myeloid dendritic cells in combination with talimogene laherparepvec in immune checkpoint blockade refractory advanced melanoma patients: a phase I clinical trial. J Immunother Cancer. 2022 Sep;10(9):e005141. doi: 10.1136/jitc-2022-005141.

  PMID: 36113895 DERIVED

MeSH Terms

Conditions

Melanoma

Interventions

talimogene laherparepvec

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

Study Officials

• Bart Neyns, MD,PhD

  Universitair Ziekenhuis Brussel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Intratumoral injection of T-VEC followed by intratumoral injection of CD1c (BDCA-1)+ myDC

Study Record Dates

• First Submitted: November 16, 2018
• First Posted: November 20, 2018
• Study Start: September 28, 2018
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: December 29, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)