Intratumoral Injection of Autologous CD1c (BDCA-1)+ MyDC, Avelumab, and Ipilimumab Plus Systemic Nivolumab

NCT03707808 | Recruiting Phase 1

• 1 other identifier: 2017-BN-003
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial aims at investigating the role and effect of autologous CD1c (BDCA-1)+ myeloid dendritic cells in combination with intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the immunoligand AS01B compared to a combinatorial immunotherapy regimen using intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the immunoligand AS01B. Concomitantly, nivolumab (a PD-1 blocking mAb) will be administered intravenously in both arms.

Conditions

Solid Tumor; Metastases to Soft Tissue

Keywords

solid tumors

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of Treatment-related Adverse Events graded according to CTCAE of intratumoral injection of autologous CD1c (BDCA-1)+ myDC plus avelumab and ipilimumab in combination with iv nivolumab

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

  1 year

• To assess the therapeutic efficacy and toxicity of the AS01B adjuvants in combination with systemic PD-1 blockade and intratumoral CTLA-4 inhibition plus intratumoral administration of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC co-product in patients

  1-year progression free survival (PFS) rate following randomization.

  1 year

• Feasibility of treatment strategy

  Percentage of study patients that can receive the planned CD1c (BDCA-1)+ / CD141(BDCA-3)+ myDC intratumoral injection.

  1 year

Secondary Outcomes (6)

• Objective response rate (ORR) of intratumoral injected CD1c (BDCA-1)+ myDC, avelumab, and ipilimumab plus iv nivolumab

  1 year

• Treatment disposition

  1 year

• Anti-tumor activity

  1 year

• Duration of response (DOR)

  1 year

• Progression-free survival (PFS)

  1 year

Other Outcomes (2)

• Effect on cellular- and molecular characteristics of the tumor microenvironment during/following study treatment

  1 year

• Effect of study treatment on blood lymphocytes

  1 year

Study Arms (2)

Immediate treatment

EXPERIMENTAL

IT injection of MyDC, ipilimumab and AS01b + IV nivolumab

Drug: intratumoral injection of autologous CD1c (BDCA-1)+ myDC; Drug: Intratumoral injection of ipilimumab and AS01b; Drug: IV nivolumab

Delayed treatment

ACTIVE COMPARATOR

IT injection of ipilimumab and AS01b + IV nivolumab

Drug: Intratumoral injection of ipilimumab and AS01b; Drug: IV nivolumab

Interventions

intratumoral injection of autologous CD1c (BDCA-1)+ myDC DRUG

intratumoral injections plus intravenous administration

Also known as: intratumoral injection of ipilimumab and avelumab, intravenous nivolumab

Immediate treatment

Intratumoral injection of ipilimumab and AS01b DRUG

Intratumoral injection of ipilimumab and AS01b

Delayed treatment; Immediate treatment

IV nivolumab DRUG

Nivolumab administered intravenously

Delayed treatment; Immediate treatment

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
• Histologically confirmed advanced solid tumor that cannot be completely surgically resected
• Failing all standard curative and live prolonging therapy.
• Presence of skin- or lymphnode metastatic disease amenable to intratumoral injection by manual palpation, US or CT-guidance. At least one metastatic lesion should be amenable to a safe post-injection biopsy (by core needle biopsy, partial- or complete surgical resection).
• ECOG performance status of 0 or 1
• Candidate for intralesional therapy defined as either one of the following:
• At least 1 injectable skin or lymph node metastatic lesion with a longest diameter of ≥ 10 mm
• Multiple injectable tumor lesions that in aggregate have a longest diameter of ≥ 10 mm injectable disease
• Adequate organ function determined within 14 days prior to enrollment, defined as follows:
• Hematological: absolute neutrophil count ≥ 1500/mm3 (1.5x109/L), platelet count: ≥ 100.000/mm3 (7.5x109/L), hemoglobin: ≥ 9 g/dL (without need for hematopoietic growth factor or transfusion support)
• Renal: 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).
• Hepatic: serum bilirubin: 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level \> 1.5 x ULN, aspartate aminotransferase (AST): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases, alanine aminotransferase (ALT): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases
• Coagulation: 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, 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 anticoagulants
• 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.

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 \>8 mg/day of methylprednisone 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 (eg, 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 immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia)
• History of other malignancy within the past 5 years with the following exceptions: 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, adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment, adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment, adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment , prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment, adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment
• Prior treatment of other tumor vaccine
• 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.
• History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. 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.
• Evidence of clinically significant immunosuppression such as the following: diagnosis of immunodeficiency, concurrent opportunistic infection, receiving systemic immunosuppressive therapy (\> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses \> 10 mg/day of prednisone or equivalent except for management of adverse events and central nervous system (CNS) metastases during the course of the study. Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.
• Known human immunodeficiency virus (HIV) disease
• Known acute or chronic hepatitis B or hepatitis C infection
• Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment
• Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of study treatment. Note: Women not of childbearing potential are defined as: postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women \< 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.) OR have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR has a congenital or acquired condition that prevents childbearing. Note: Acceptable methods of effective contraception are defined in the informed consent form.

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (1)

UZ Brussel

Jette, Brabant, 1090, Belgium

RECRUITING

Related Publications (1)

• Tijtgat J, Geeraerts X, Boisson A, Stevens L, Vounckx M, Dirven I, Schwarze JK, Raeymaeckers S, Forsyth R, Van Riet I, Tuyaerts S, Willard-Gallo K, Neyns B. Intratumoral administration of the immunologic adjuvant AS01B in combination with autologous CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells plus ipilimumab and intravenous nivolumab in patients with refractory advanced melanoma. J Immunother Cancer. 2024 Jan 11;12(1):e008148. doi: 10.1136/jitc-2023-008148.

  PMID: 38212127 DERIVED

MeSH Terms

Interventions

avelumab; Nivolumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Bart Neyns, MD, PhD

CONTACT

+3224775447; bart.neyns@uzbrussel.be

Study Design

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

Model Details: There are 2 arms that are given treatment in parallel. But pts from the second arm without the myDC are able to crossover to the first arm with the myDC's. But not the other way around.

Study Record Dates

• First Submitted: February 5, 2018
• First Posted: October 16, 2018
• Study Start: January 29, 2018
• Primary Completion: December 24, 2025
• Study Completion: December 24, 2025
• Last Updated: January 20, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)