Abstract
Advances in immunotherapy utilizing immune checkpoint inhibitors (ICIs) have transformed the treatment landscapes of several malignancies in recent years. Oncologists are now tasked with extending these benefits to a greater number of patients and tumor types. Metastatic castration-resistant prostate cancer (mCRPC) infrequently responds to ICIs, while the cellular vaccine approved for mCRPC, sipuleucel-T, provides a 4-month survival benefit but does not produce clinical responses as monotherapy. However, many novel and generally well-tolerated immune oncology agents with potential for immune synergy and/or additive effects are undergoing clinical development. This availability presents opportunities to develop adaptive-design combination clinical trials aimed to generate, expand, and facilitate antitumor immune responses. Here we describe a currently accruing phase I/II trial (NCT03493945) testing a brachyury-targeted antitumor vaccine, TGF-β TRAP/anti-PD-L1 antibody, an IL-15 agonist, and an IDO1 inhibitor in mCRPC.
Trial registration:
This trial ( NCT03493945 ) was registered in National Clinical Trials on April 11th 2018.
Keywords:
ALT-803; Brachyury; Combination immunotherapy; IDO1; IL-15; M7824; Metastatic castration-resistant prostate cancer; PD-L1; TGF-β; Tumor vaccine.
Publication types
-
Clinical Trial, Phase I
-
Clinical Trial, Phase II
MeSH terms
-
Antibodies, Bispecific / therapeutic use*
-
Antineoplastic Agents / therapeutic use
-
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
-
B7-H1 Antigen / antagonists & inhibitors
-
Cancer Vaccines / therapeutic use*
-
Fetal Proteins / therapeutic use*
-
Humans
-
Immunotherapy
-
Indoleamine-Pyrrole 2,3,-Dioxygenase / antagonists & inhibitors
-
Interleukin-15 / antagonists & inhibitors
-
Male
-
Oximes / therapeutic use*
-
Prostatic Neoplasms, Castration-Resistant / drug therapy*
-
Proteins / therapeutic use
-
Recombinant Fusion Proteins
-
Sulfonamides / therapeutic use*
-
T-Box Domain Proteins / therapeutic use*
-
Tissue Extracts / therapeutic use*
-
Transforming Growth Factor beta / antagonists & inhibitors
-
Treatment Outcome
-
Vaccines, DNA
-
Viral Vaccines / therapeutic use*
Substances
-
ALT-803
-
Antibodies, Bispecific
-
Antineoplastic Agents
-
B7-H1 Antigen
-
CD274 protein, human
-
Cancer Vaccines
-
Fetal Proteins
-
IDO1 protein, human
-
IL15 protein, human
-
Indoleamine-Pyrrole 2,3,-Dioxygenase
-
Interleukin-15
-
MVA vaccine
-
Oximes
-
Proteins
-
Recombinant Fusion Proteins
-
Sulfonamides
-
T-Box Domain Proteins
-
Tissue Extracts
-
Transforming Growth Factor beta
-
Vaccines, DNA
-
Viral Vaccines
-
epacadostat
-
sipuleucel-T
-
Brachyury protein
Associated data
-
ClinicalTrials.gov/NCT03493945