rasdegafusp alfa (CDX-1401)

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

Background: Patients with intermediate and higher-risk MDS are generally treated with the DNA hypomethylating agents (HMAs) azacytidine and decitabine...This open-label, non-randomized single center Phase 1 study used an HLA unrestricted NY-ESO-1 vaccine (CDX-1401 (1 mg) + poly-ICLC (1.8 mg)) in combination with standard dose decitabine (20mg/m2/d x 5 days) and nivolumab (3 mg/kg every 2 weeks), 4 cycles of combination therapy were planned on study; patients deriving clinical benefit could continue treatment at the discretion of the treating physician... These results suggest that the use of immunotherapy to induce effective, cytotoxic anti-tumor T cell responses depends upon the myeloid immunologic milieu in MDS patients. The critical importance of cDC1 function has recently been described and appreciated in the context of solid tumor immunotherapy. The observation of both numerical and functional defects of this cell population in patients with myeloid neoplasia provides a possible explanation for the disappointing efficacy of immunotherapies in this disease state.

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024

We evaluated a regimen of Flt3L (CDX-301) to increase DCs and other antigen-presenting cells, poly-ICLC (TLR3 agonist that activates DCs) and a vaccine comprising anti-DEC-205-NY-ESO-1, a fusion antibody targeting CD205, linked to NY-ESO-1. Transcriptional analyses revealed gene signatures associated with CDX-301 induction of an early, durable immune response. This study reveals in vivo effects of Flt3L on innate immune cells in the setting of vaccination, leading to an immunogenic vaccine regimen.

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2022 --> Mar 2023 | Trial primary completion date: Mar 2022 --> Mar 2023

P2, N=60, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

P1, N=8, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed

P1/2, N=40, Completed, Roswell Park Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Aug 2021 --> Aug 2020

P1/2, N=40, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Mar 2022 --> Aug 2021 | Trial primary completion date: Mar 2021 --> Aug 2020

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2021 --> Mar 2022 | Trial primary completion date: Mar 2021 --> Mar 2022

P1/2, N=40, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Feb 2023 --> Mar 2022 | Trial primary completion date: Feb 2022 --> Mar 2021

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Suspended --> Active, not recruiting

These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141 DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies.

P1/2, N=75, Suspended, National Cancer Institute (NCI) | Trial completion date: Mar 2020 --> Mar 2021 | Trial primary completion date: Mar 2020 --> Mar 2021