Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC) : Phase I/II Study of the Combination Immunotherapy Regimen: SX-682, TriAdeno Vaccine, Retifanlimab and IL-15 Agonist N-803 (STAR15) for Metastatic Colorectal Cancer (mCRC)

Background:mCRC is incurable and available standard therapies offer a median overall survival of approximately 2 years.Most cases (approximately 95%) of mCRC have an intact expression of DNA mismatch repair enzymes (MLH1, MSH2, MSH6, and PMS2), and are commonly classified as having mismatch repair proficient (pMMR) or microsatellite stable (MSS) mCRC.MSS mCRC does not respond to immune checkpoint inhibitor (ICI) therapy whereas mismatch repair deficient (or microsatellite instability-high) mCRC is responsive to ICI therapy.Preclinical and clinical studies conducted at the NCI in the Laboratory of Tumor Immunology Biology (LTIB) indicate that the combination of programmed cell death protein 1 (PD-1) / Programmed death-ligand 1 (PD-L1) blockade, tumor-associated antigens (TAA) targeted vaccine, IL15 agonist, and CXCR1/2 inhibition may include sufficient immune enhancements to produce anti-tumor activity in MSS mCRC.Retifanlimab is a humanized IgG4 monoclonal antibody that targets PD-1. Retifanlimab has been studied in several clinical trials, and several malignancies, and has a safety and clinical activity profile similar to approved anti-PD-1 therapies (e.g., pembrolizumab).The TriAdeno Vaccine employs 3 adenovirus serotype 5 vectors, encoding three TAAs (CEA, MUC1, and brachyury). These vaccines have completed the phase 1 study and are safe and well tolerated. Vaccination generates antigen-specific T cell responses to CEA, MUC1, and brachyury.N-803 is an IL-15 agonist that activates and expands T cells and NK cells. N-803 enhances anti-tumor activity in combination with tumor-targeted vaccines. Clinically, multiple studies have demonstrated the safety of tumor-targeted vaccine in combination with PD- 1/PD-L1 blockade. Adding N-803 to PD-1/PD-L1 blockade can produce antitumor responses in disease states where responses to PD-1/PD-L1 alone would not be expected.SX-682 is a small molecule, orally bioavailable, allosteric antagonist of the chemokine receptors CXCR1 and CXCR2. Inhibition of CXCR1 and CXCR2 addresses a major component of intratumoral T cell suppression by myeloid-derived suppressor cells and tumor-associate macrophages. SX-682 has shown to be tolerable in combination with PD- 1/PD-L1 blockade.Objectives:Phase I: to describe the safety profile of the Immuno-Oncology (IO) regimens consisting of retifanlimab, TriAdeno vaccine, N-803 (A1), and retifanlimab, TriAdeno vaccine, N- 803, SX 682 (A2) in participants with metastatic colorectal cancer (mCRC).Phase II: to determine the objective response rate (ORR) (complete response (CR) + partial response (PR)) of the IO regimen in mCRC.Eligibility:Age >=18 years.Previously treated metastatic colorectal cancer with measurable disease.Eastern Cooperative Oncology Group (ECOG) performance status <= 2.Adequate organ function.Design:This is an open-label Phase I/II trial to evaluate the safety and efficacy of the Immuno- Oncology regimen, consisting of retifanlimab, TriAdeno vaccine, N-803, and SX-682 in participants with mCRC.During Phase I, we will assess the safety of the three- and the four-drug IO regimens.During Phase II we will continue to evaluate the safety and examine the efficacy of the four drug IO regimen. If 0 to 1 of the first 9 participants treated with the 4-drug IO regimen have a clinical response, defined as complete response (CR) + partial response (PR) within the first 24 weeks after treatment initiation, then no further participants will be accrued using the quadruple combination. If 2 or more of the first 9 participants have a response, then accrual will continue until a total of 23 evaluable participants have been treated with a four-drug IO regimen.Participants will receive treatment in cycles consisting of 28 (+7) days for 2 years.To allow for a small number of inevaluable participants, and screen failures the accrual ceiling will be set at 60..

Medienart:	Klinische Studie

Erscheinungsjahr:	2024
Erschienen:	2024

Enthalten in:	ClinicalTrials.gov - (2024) vom: 29. März Zur Gesamtaufnahme - year:2024

Sprache:	Englisch

Links:	Volltext [kostenfrei]

Themen:	610 Colorectal Neoplasms Phase: Phase 1, Phase 2 Recruitment Status: Recruiting Study Type: Interventional

Anmerkungen:	Source: Link to the current ClinicalTrials.gov record., First posted: November 29, 2023, Last downloaded: ClinicalTrials.gov processed this data on April 03, 2024, Last updated: April 03, 2024

Study ID:	NCT06149481 10001563 001563-C
Veröffentlichungen zur Studie:

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PPN (Katalog-ID):	CTG000014680