Nivolumab With Ipilimumab Combined With TGFβ-15 Peptide Vaccine and Radiotherapy for Pancreatic Cancer

NCT05721846 | Active Not Recruiting Phase 1

• 1 other identifier: PA 2217
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

"Non-immunogenicity" of PC with high prevalence of immunosuppressive cells and typically a scarcity of tumor-infiltrating effector lymphocytes is considered as one of the reasons for lacking responsiveness to single-agent immunotherapies. Considering the emerging role of the tumor microenvironment, the combination of checkpoint blocking antibodies with immunomodulation of the tumor microenvironment could lead to better responses in tumor historically resistant to radiation and checkpoint blocking antibody approaches as single modalities. For example, the data from the phase 2 study CheckPAC (NCT02866383) showed durable clinical benefit in a small subgroup of patients after adding SBRT of 15 Gy to a combination of nivolumab and ipilimumab (presented at ASCO GI 2022, San Fransisco) in patients with resistant metastatic PC. Furthermore, we have found that the TGFβ-15 immune response is corelated to clinical benefit, supporting the rationale for combining of TGFβ-15 peptide vaccine with CheckPAC strategy (SBRT of 15 in combination with nivolumab and ipilimumab).

Conditions

Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Adverse events

  6 months

Secondary Outcomes (6)

• Overall response rate

  12 months

• Overall survival

  12 months

• Progression free survival

  6 months

• Duration of response

  12 months

• Best overall response

  6 months

Study Arms (1)

Experimental

EXPERIMENTAL

SBRT: 15 Gy x 1 on a single site of disease on day 1 cycle 1 Immunotherapy: Nivolumab 3 mg/kg (up to 240 mg maximum) as i.v. infusion on day 1 (± 3 days) of each 14-day treatment cycle Ipilimumab 1 mg/kg as i.v. infusion on day 1 cycle 1 and subsequently every 6 weeks (± 3 days). Vaccine (500 μl aqueous solution of 200 μg TGFβ-B-15 peptide mixed to an emulsion with 500μl Montanide ISA-51) as s.c. injection on day 1 of the first 6 cycles and subsequently every 4 weeks (± 3 days)

Drug: Nivolumab; Drug: Ipilimumab; Radiation: SBRT; Biological: TGFβ-B-15 peptide

Interventions

Nivolumab DRUG

3 mg/kg (up to 240 mg maximum) as i.v. infusion on day 1 (± 3 days) of each 14-day treatment cycle

Experimental

Ipilimumab DRUG

1 mg/kg as i.v. infusion on day 1 cycle 1 and subsequently every 6 weeks (± 3 days)

Experimental

SBRT RADIATION

SBRT: 15 Gy x 1 on a single site of disease on day 1 cycle 1

Experimental

TGFβ-B-15 peptide BIOLOGICAL

Vaccine (500 μl aqueous solution of 200 μg TGFβ-B-15 peptide mixed to an emulsion with 500μl Montanide ISA-51) as s.c. injection on day 1 of the first 6 cycles and subsequently every 4 weeks (± 3 days)

Experimental

Eligibility Criteria

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

You may qualify if:

• Signed informed consent
• Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• Histological or cytological confirmation of advanced pancreatic carcinoma prior to entering this study
• Prior therapy requirements:
• There is no upper limit on the number of prior chemotherapy regimens received. Participants must have received and progressed during or after at least 1 line of systemic chemotherapy in the metastatic setting (gemcitabine or 5-FU based regimens).
• Notes:
• If a participant received adjuvant/neoadjuvant systemic combinational therapy, and progressed within 6 months, the adjuvant/neoadjuvant treatment will be considered as 1 line of systemic treatment.
• In general, discontinuation of 1 drug in a multi-drug regimen and continuation of other drug(s), is considered part of the same line of treatment. Restarting the same regimen after a drug holiday or maintenance chemotherapy can also be considered part of the same line of treatment. Switching from IV (5-FU) to an oral formulation (capecitabine) of the same drug is also considered part of the same line of treatment
• Minimum time from first systemic therapy for recurrent/metastatic adenocarcinoma of pancreas to progression should be at least 3 months
• Age 18 years and older
• ECOG Performance Status (PS) 0-1
• All participants will be required to undergo mandatory pre- and on-treatment biopsies at acceptable clinical risk as judged by the investigator. An archival pre-treatment sample is not acceptable.
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L

You may not qualify if:

• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
• Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Participants with active, known or suspected autoimmune disease. Participants are permitted to enroll with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab, ipilimumab and radiation in combination with TGFβ-15 peptide vaccine. The following are exceptions to this criterion:
• Intranasal, inhaled, or topical steroids; or local steroid injections (e.g. intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
• Participants should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• WOCBP who are pregnant or breastfeeding

Sponsors & Collaborators

• Inna Chen, MD: lead

Study Sites (1)

Herlev & Gentofte University Hospital, Denmark

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Lead of the Pancreatic Cancer Center

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 10, 2023
• Study Start: May 3, 2023
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: September 12, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)