Mobista (CDX-301)

P1, N=30, Recruiting, University of Texas Southwestern Medical Center | Trial completion date: Apr 2025 --> Apr 2026 | Trial primary completion date: Apr 2025 --> Apr 2026

P1, N=30, Recruiting, Dana-Farber Cancer Institute | Trial completion date: Jan 2027 --> Sep 2030 | Trial primary completion date: Jan 2025 --> Dec 2026

Here, we report the results of a Phase II clinical trial where twenty-nine patients with advanced, previously treated NSCLC were treated with stereotactic body radiotherapy (SBRT) targeting a single site of disease along with CDX-301, a recombinant human Fms-like tyrosine kinase 3 ligand (FLT3L)...These coordinated immune responses were sustained for over 4 weeks in responders, highlighting a potential therapeutic axis engaged in a systemic immune response against multiple lesions in NSCLC. Overall, these findings underscore the potential of combining in situ vaccination, using SBRT, with strategies to enhance the activation of innate immune cells, such as DCs through FLT3L, to potentiate robust anti-tumor T cell responses.

Cohort B, which combined radiation therapy with CDX-301, poly-ICLC, and nivolumab, demonstrated encouraging clinical activity. Pre-existing rather than treatment-induced immune activation was associated with clinical benefit across cohorts, highlighting the importance of baseline immune fitness.

P2, N=33, Completed, Albert Einstein College of Medicine | Active, not recruiting --> Completed

P1, N=18, Recruiting, University of Southern California | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2025 --> Jan 2026

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.