Mobista (CDX-301)

P1; N=45 --> 30

P2, N=33, Active, not recruiting, Albert Einstein College of Medicine | Completed --> Active, not recruiting | Trial completion date: Oct 2022 --> Oct 2024

P1, N=30, Recruiting, Dana-Farber Cancer Institute | N=20 --> 30

P2, N=16, Terminated, Washington University School of Medicine | N=24 --> 16 | Trial completion date: Mar 2024 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: Mar 2024 --> Nov 2023; Celldex decision

This is a single arm phase I pilot study of liposomal doxorubicin, CDX-1140 (CD40 agonist monoclonal antibody), and CDX-301 (recombinant Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic TNBC. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line treatment for metastatic disease (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999) and is currently open at University of Texas Southwestern Medical Center, Texas Oncology, University of Chicago, University of Texas San Antonio, Sarah Cannon Research Institute, and Johns Hopkins.

In this study, we investigated whether monocyte vaccination in combination with CDX-301, a DC-expanding cytokine Fms-like tyrosine kinase 3 ligand (Flt3L), could improve the antitumor efficacy of anti-programmed cell death (anti-PD-1) immune checkpoint blockade...To our knowledge, this is the first demonstration that a cancer vaccine strategy and Flt3L can improve the antitumor efficacy of anti-PD-1. The findings presented here warrant further study of how monocyte vaccines can improve Flt3L and immune checkpoint blockade as they enter clinical trials.

P1/2, N=5, Terminated, Albert Einstein College of Medicine | N=46 --> 5 | Trial completion date: Aug 2024 --> Aug 2022 | Recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Aug 2022; Low accrual

P1; Trial completion date: Apr 2026 --> Apr 2025

P2, N=100, Recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2025

P1, N=18, Recruiting, University of Southern California | Not yet recruiting --> Recruiting

P1; Trial completion date: Oct 2024 --> Apr 2026 | Trial primary completion date: Oct 2024 --> Apr 2025

CDX-301 will be discontinued after 2 cycles; liposomal-doxorubicin and CDX-1140 will be continued until disease progression or clinically limiting toxicities. Key eligibility criteria are unresectable stage III or stage IV TNBC (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre- treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites (NCT05029999).

P1, N=18, Not yet recruiting, University of Southern California | Trial completion date: Nov 2024 --> Sep 2025 | Trial primary completion date: Nov 2023 --> Sep 2024

P2, N=100, Recruiting, Weill Medical College of Cornell University | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2021 --> Dec 2023

P1; Not yet recruiting --> Recruiting

This is a single arm phase I pilot study of liposomal-doxorubicin, CDX-1140 (CD40 agonist), and CDX-301 (Flt3 ligand) combination therapy in patients with metastatic or unresectable locally advanced metastatic triple-negative breast cancer. Key eligibility criteria are unresectable stage III or stage IV triple-negative breast cancer (ER ≤10%, PR ≤10%, HER2/neu negative), 1st to 3rd line metastatic treatment setting (1st line patients need to be PD-L1 negative by 22C3 assay), measurable disease by RECIST 1.1 criteria, consent for pre-treatment and on-treatment biopsies of amenable soft tissue tumor lesions, no prior treatment with an anti-CD40 antibody or a Flt3 ligand, no anthracycline treatment in the metastatic setting, no prior progression while on anthracycline-based therapy or within 6 months of completing neoadjuvant chemotherapy, and no history of non-infectious pneumonitis or current pneumonitis. This trial will enroll up to 45 patients across multiple sites.

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; Initiation date: Feb 2022 --> Jun 2022

P1, N=0, Withdrawn, Roswell Park Cancer Institute | N=36 --> 0 | Not yet recruiting --> Withdrawn

P1, N=36, Not yet recruiting, Roswell Park Cancer Institute | Trial completion date: Nov 2023 --> Nov 2024 | Trial primary completion date: Nov 2022 --> Nov 2023

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

P1, N=45, Not yet recruiting, University of Texas Southwestern Medical Center

P1, N=36, Not yet recruiting, Roswell Park Cancer Institute

P2, N=100, Recruiting, Weill Medical College of Cornell University | Active, not recruiting --> Recruiting

P2, N=100, Active, not recruiting, Weill Medical College of Cornell University | Recruiting --> Active, not recruiting

P2, N=100, Recruiting, Weill Medical College of Cornell University | Not yet recruiting --> Recruiting