Clinical Trial of SBRT and Systemic Pembrolizumab With or Without Avelumab/Ipilimumab+ Dendritic Cells in Solid Tumors

NCT04571632 | Unknown Phase 2

• 1 other identifier: 2019-BN-001
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

A randomized phase II clinical trial of SBRT and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors.

Conditions

Non Small Cell Lung Cancer; Solid Tumor

Outcome Measures

Primary Outcomes (1)

• 1 year progression free survival

  1 year progression free survival

  1 year

Secondary Outcomes (1)

• Adverse events

  up to 3 years

Study Arms (2)

Immediate treatment arm:

ACTIVE COMPARATOR

On day -3, -1 and 1, SBRT fractions of 8 Gy will be administered to subjects. On day 1, approximately 2 hours after the last SBRT fraction, intratumoral injection of ipilimumab (Yervoy®, 50mg/10mL solution) at a maximum total dose of 10 mg (= 2 ml of a 50mg/10ml solution) and avelumab (Bavencio®, 200mg/10mL solution) at maximum total dose of 40 mg (= 2 ml of a 200mg/10ml solution) will be performed. Subject will also receive a standard 200mg (fixed dose) intravenous infusion of pembrolizumab (Keytruda®, 100 mg/4mL solution). On day 2, autologous, non-substantially manipulated CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be intratumorally administered. Previously cryopreserved CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be thawed before administration. On day 21 and every 21 days thereafter, IT injection of ipilimumab and avelumab and IV pembrolizumab at the same dose as on day 1 will be performed. Treatment will be discontinued upon disease progression

Drug: Avelumab; Drug: Ipilimumab 5 MG/ML; Drug: Pembrolizumab 100 MG in 4 ML Injection; Other: CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC

Contemporary control arm

ACTIVE COMPARATOR

On day -3, -1 and 1, SBRT fractions of 8 Gy will be administered to subjects. On day 1 and every + 21 days thereafter, subjects will receive a standard 200mg (fixed dose) IV pembrolizumab (Keytruda®, 100 mg/4mL solution) dose. On disease progression, intratumoral administration as in the "immediate-treatment" arm will be conducted. Thus, intratumoral injection of ipilimumab at a maximum total dose of 10 mg and avelumab at maximum total dose of 40 mg will be performed. Administration of pembrolizumab at a dose of 200 mg will be continued. Tumor response assessments by whole body PET/CT will be scheduled in week 12 and every 12 weeks thereafter during the treatment phase; . Baseline scan will be performed during screening period Procurement of tumor tissue by fine needle aspirates will be performed at the time of every intra-tumoral study drug administration

Drug: Avelumab; Drug: Ipilimumab 5 MG/ML; Drug: Pembrolizumab 100 MG in 4 ML Injection; Other: CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC

Interventions

Avelumab DRUG

Avelumab (200mg/10mL solution) will be administered by intratumoral injection at a maximum total dose of 40 mg (= 2 ml of a 200mg/10ml solution) on day 1 followed by a subsequent intratumoral injections on day 15, 29, 43, 57 and 71. Total administered dose of avelumab (200mg/10mL solution) will be up to 2.0 mL per treatment. Injected volume per lesion will range from 0.05 mL for lesions \< 0,5 cm to 2.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in individual patients will not be required.

Also known as: Bavencio

Contemporary control arm; Immediate treatment arm:

Ipilimumab 5 MG/ML DRUG

Ipilimumab (50mg/10mL solution) will be administered by intratumoral injection at a maximum total dose of 10 mg (= 2 ml of a 50mg/10ml solution) on day 1 followed by a subsequent intratumoral injections on day 15, 29, 43, 57 and 71. Total administered dose of ipilimumab (50mg/10mL solution) will be up to 2.0 mL per treatment. Injected volume per lesion will range from 0.05 mL for lesions \< 0,5 cm to 2.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in individual patients will not be required. Determination of ipilimumab (50mg/10mL solution) injection volume based on lesion size

Also known as: Yervoy

Contemporary control arm; Immediate treatment arm:

Pembrolizumab 100 MG in 4 ML Injection DRUG

The first administration of pembrolizumab 200 mg (100 mg/4mL solution) by the intravenous route during 30 minutes will be administered on day 1. The second administrations of pembrolizumab 200 mg will be administered by a 30 minutes intravenous infusion on day 21, and thereafter every 21 days (or up to ± 3 days before or after the scheduled date if necessary) days.

Also known as: Keytruda

Contemporary control arm; Immediate treatment arm:

CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC OTHER

CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC will be administered by intratumoral injection in the lesions that were injected by avelumab en ipilimumab on day 1 (approximately 24 hours after intratumoral injection of avelumab en ipilimumab). The total administered CD1c (BDCA-1)+/ CD141 (BDCA-3)+ myDC volume will be up to 4.0 mL per intratumoral treatment session. Injected volume per lesion (skin-, soft tissue or lymph-node metastases) will range from 0.1 mL for lesions \< 0,5 cm to 4.0 mL for lesions \> 5 cm in longest diameter. Injection of all lesions in an individual patient will not be required. The determination of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC injection volume is based on lesion size. When lesions are clustered together, they are injected as a single lesion according to the table for determination of CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDC injection volume based on lesion size.

Contemporary control arm; Immediate treatment arm:

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 written 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 solid tumors that cannot be completely surgically resected All subjects must have received prior pembrolizumab or nivolumab (with or without cytotoxic chemotherapy or other additional drugs) and fail to respond to this treatment (patients must be documented with stable or progression of disease as their best response to this first-line therapy).
• Oligometastatic" disease defined by a number of metastatic sites 7
• ECOG performance status of 0 or 1
• Patients need to have ≥ 1 metastatic lesion (≥ 10 mm in longest diameter) that can be safely injected by ultrasound-/ CT-guidance, by endo-bronchial ultrasound (EBUS) or even clinically. The lesion should also be amenable for safe biopsy.
• Injectable metastasis need(s) to be eligible for SBRT
• Adequate organ function determined within 14 days prior to enrollment
• 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 (a representative archival tissue sample obtained prior to study participation or newly obtained biopsy). Subject must submit the tumor sample during screening. Subjects with a nonevaluable 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.
• Subjects should have adequate vascular access to undergo a leukapheresis

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 study 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 leptomeningeal metastasis which is excluded regardless of clinical condition.
• History or evidence of active autoimmune disease that requires systemic treatment 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 serious immune related adverse event during treatment with pembrolizumab in first-line
• History of other malignancy within the past 5 years of enrollment Prior treatment with immune-checkpoint inhibitors (including but not restricted to PD-1, PD-L1 and CTLA-4 blocking mAb) 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. Subjects should not have ongoing grade 3 or 4 immune-related or chemotherapy-related adverse events. 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
• Evidence of clinically significant immunosuppression
• Known human immunodeficiency virus (HIV) disease
• Known acute or chronic hepatitis B or hepatitis C infection
• Known syphilis infection
• Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 6 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 6 months after the last dose of study treatment Postmenopausal (therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.) Male subject who is unwilling to use acceptable method of effective contraception during trial participation and through 6 months after the last dose of study treatment. For this trial, male subjects will be considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition). Note: Acceptable methods of effective contraception are defined in the informed consent form.
• Subject has known sensitivity to any of the products or components to be administered during dosing.
• Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge

Sponsors & Collaborators

• Universitair Ziekenhuis Brussel: lead

Study Sites (2)

Universitair Ziekenhuis Brussel

Jette, Brussels Capital, 1090, Belgium

RECRUITING

Uz Brussel

Brussels, 1090, Belgium

RECRUITING

Related Publications (1)

• Vounckx M, Tijtgat J, Stevens L, Dirven I, Ilsen B, Vandenbroucke F, Raeymaeckers S, Vekens K, Forsyth R, Geeraerts X, Van Riet I, Schwarze JK, Tuyaerts S, Decoster L, De Ridder M, Dufait I, Neyns B. A randomized phase II clinical trial of stereotactic body radiation therapy (SBRT) and systemic pembrolizumab with or without intratumoral avelumab/ipilimumab plus CD1c (BDCA-1)+/CD141 (BDCA-3)+ myeloid dendritic cells in solid tumors. Cancer Immunol Immunother. 2024 Jul 2;73(9):167. doi: 10.1007/s00262-024-03751-0.

  PMID: 38954010 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; Ipilimumab; pembrolizumab; Injections; Antigens, CD1d

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Drug Administration Routes; Drug Therapy; Therapeutics; Antigens, CD1; Antigens, CD; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Antigens, Differentiation, T-Lymphocyte; Biomarkers

Central Study Contacts

BART NEYNS, MD PHD

CONTACT

+32 2 477 60 40; bart.neyns@uzbrussel.be

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2020
• First Posted: October 1, 2020
• Study Start: September 22, 2020
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 14, 2022

Record last verified: 2022-02

Locations

BE (2)