rasdegafusp alfa (CDX-1401) / Celldex - LARVOL DELTA

Checkpoint Immunotherapy Is Associated with Preferential Activation of Tumor-Antigen Specific CD4+ T Cells in MDS (ASH 2023) - "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..."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Solid Tumor • CD4 • CD8 • CTAG1B

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | N=75 ➔ 12

Enrollment change • IO biomarker • Trial completion • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2024 ➔ Mar 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2023 ➔ Mar 2024 | Trial primary completion date: Mar 2023 ➔ Mar 2024

IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

Flt3 ligand augments immune responses to anti-DEC-205-NY-ESO-1 vaccine through expansion of dendritic cell subsets. (PubMed, Nat Cancer) - P2 | "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."

Clinical • IO biomarker • Journal • P2 data • Melanoma • Oncology • Solid Tumor • CDK1 • CTAG1B • FLT3

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=75 | Active, not recruiting | Sponsor: National Cancer Institute (NCI) | Trial completion date: Mar 2022 ➔ Mar 2023 | Trial primary completion date: Mar 2022 ➔ Mar 2023

IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PD-L1

A Vaccine (CDX-1401) With or Without a Biologic Drug (CDX-301) for the Treatment of Patients With Stage IIB-IV Melanoma (clinicaltrials.gov) - P2; N=60; Completed; Sponsor: National Cancer Institute (NCI); Active, not recruiting ➔ Completed

Clinical • Trial completion • Cutaneous Melanoma • Eye Cancer • Melanoma • Mucosal Melanoma • Ocular Melanoma • Oncology • Solid Tumor • CD4 • CTAG1B • PRAME

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, Decitabine, and Nivolumab in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=8; Completed; Sponsor: Roswell Park Cancer Institute; Active, not recruiting ➔ Completed

Clinical • Trial completion • Acute Myelogenous Leukemia • Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • CTAG1B

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission (clinicaltrials.gov) - P1/2; N=40; Completed; Sponsor: Roswell Park Cancer Institute; Active, not recruiting ➔ Completed

Trial completion • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CD4 • CD8 • CTAG1B • CTAG2 • PCR

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission (clinicaltrials.gov) - P1/2; N=40; Active, not recruiting; Sponsor: Roswell Park Cancer Institute; Trial completion date: Mar 2022 ➔ Aug 2021; Trial primary completion date: Mar 2021 ➔ Aug 2020

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CD4 • CD8 • CTAG1B • CTAG2 • PCR

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2; N=75; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Trial completion date: Mar 2021 ➔ Mar 2022; Trial primary completion date: Mar 2021 ➔ Mar 2022

Clinical • IO biomarker • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG1B • PCR • PD-L1

A Trial of CDX-1401 in Combination With Poly-ICLC and Pembrolizumab, in Previously Treated Advanced Solid Tumor Patients (clinicaltrials.gov) - P1/2; N=26; Not yet recruiting; Sponsor: Case Comprehensive Cancer Center; Initiation date: Jul 2016 ➔ Dec 2016

Clinical • Combination therapy • Trial initiation date • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • CTAG1B

A Trial of CDX-1401 in Combination With Poly-ICLC and Pembrolizumab, in Previously Treated Advanced Solid Tumor Patients (clinicaltrials.gov) - P1/2; N=0; Withdrawn; Sponsor: Case Comprehensive Cancer Center; N=26 ➔ 0; Not yet recruiting ➔ Withdrawn

Clinical • Combination therapy • Enrollment change • Trial withdrawal • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • CTAG1B

A Trial of CDX-1401 in Combination With Poly-ICLC and Pembrolizumab, in Previously Treated Advanced Solid Tumor Patients (clinicaltrials.gov) - P1/2; N=26; Not yet recruiting; Sponsor: Case Comprehensive Cancer Center

Clinical • Combination therapy • New P1/2 trial • Breast Cancer • Genito-urinary Cancer • Lung Cancer • Melanoma • Mesothelioma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • Triple Negative Breast Cancer • Urothelial Cancer • CTAG1B

A Study of CDX-1401 in Patients With Malignancies Known to Express NY-ESO-1 (clinicaltrials.gov) - P1/2; N=70; Active, not recruiting; Sponsor: Celldex Therapeutics; N=48 ➔ 70

Clinical • Enrollment change • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • CTAG1B

A Study of CDX-1401 in Patients With Malignancies Known to Express NY-ESO-1 (clinicaltrials.gov) - P1/2; N=70; Active, not recruiting; Sponsor: Celldex Therapeutics; Recruiting ➔ Active, not recruiting

Clinical • Enrollment closed • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • CTAG1B

A Study of CDX-1401 in Patients With Malignancies Known to Express NY-ESO-1 (clinicaltrials.gov) - P1/2; N=70; Completed; Sponsor: Celldex Therapeutics; Trial completion date: Sep 2014 ➔ Feb 2014

Clinical • Trial completion date • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • CTAG1B

A Study of CDX-1401 in Patients With Malignancies Known to Express NY-ESO-1 (clinicaltrials.gov) - P1/2; N=70; Completed; Sponsor: Celldex Therapeutics; Active, not recruiting ➔ Completed

Clinical • Trial completion • Hematological Malignancies • Lung Cancer • Multiple Myeloma • Non Small Cell Lung Cancer • Oncology • CTAG1B

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, Decitabine, and Nivolumab in Treating Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (clinicaltrials.gov) - P1; N=8; Active, not recruiting; Sponsor: Roswell Park Cancer Institute; Trial completion date: Dec 2020 ➔ Aug 2021

Clinical • Trial completion date • Acute Myelogenous Leukemia • Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

Calling in the backup: Expanding DCs to augment vaccine responses (Fred Hutchinson Cancer Research Center) - P2; N=60; "UW/Fred Hutch Cancer Consortium members Chihiro Morishima, Mary Disis, and Mac Cheever contributed to this work....Elad Sharon..."

P2 data

DEC-205/NY-ESO-1 Fusion Protein CDX-1401, Poly ICLC, and IDO1 Inhibitor INCB024360 in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission (clinicaltrials.gov) - P1/2; N=40; Active, not recruiting; Sponsor: Roswell Park Cancer Institute; Trial completion date: Feb 2023 ➔ Mar 2022; Trial primary completion date: Feb 2022 ➔ Mar 2021

Clinical • Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • CTAG2 • PCR

[VIRTUAL] Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells (SITC 2020) - "The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1 specific naïve and memory CD8+ T cells was examined and compared to a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DC...Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro. Conclusions These data advocate human CLEC9A-NY-ESO-1 antibody as an attractive strategy for specific targeting of CD141+ DC to enhance tumour immunogenicity in NY-ESO-1-expressing malignancies."

Melanoma • Oncology • Solid Tumor • CD8 • IFNG

[VIRTUAL] Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141+ dendritic cells to activate naïve and memory NY-ESO-1-specific CD8+ T cells (SITC 2020) - "The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1 specific naïve and memory CD8+ T cells was examined and compared to a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DC...Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8+ T cells with polyclonal effector function and potent tumor killing capacity in vitro. Conclusions These data advocate human CLEC9A-NY-ESO-1 antibody as an attractive strategy for specific targeting of CD141+ DC to enhance tumour immunogenicity in NY-ESO-1-expressing malignancies."

Melanoma • Oncology • Solid Tumor • CD8 • IFNG

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2; N=75; Active, not recruiting; Sponsor: National Cancer Institute (NCI); Suspended ➔ Active, not recruiting

Clinical • Enrollment closed • IO Biomarker • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Psychiatry • Solid Tumor • CA125 • PD-L1

Atezolizumab, Guadecitabine, and CDX-1401 Vaccine in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2; N=78; Not yet recruiting; Sponsor: National Cancer Institute (NCI)

New P1/2 trial • Biosimilar • Non-Hodgkin’s Lymphoma • Ovarian Cancer