CDX-301

Overview

CDX-301 (recombinant human Flt3 ligand; Flt3L; historically MOBIST) is a hematopoietic cytokine that binds the FLT3 (CD135) receptor. In humans, it expands dendritic-cell (DC) subsets and hematopoietic stem/progenitor cells, supporting its evaluation as an immune-priming agent and as a mobilizer for hematopoietic stem cell transplantation. A Phase 1 study in healthy volunteers showed biological activity and acceptable tolerability; subsequent clinical work has explored CDX-301 as a DC-expanding primer for cancer vaccination and in situ immunomodulation, and as a potential mobilization strategy for stem-cell donors. (nature.com)

Mechanism of action

Flt3L is the natural ligand for FLT3 (CD135) on hematopoietic stem/progenitor cells and steady-state DCs. Exogenous CDX-301 increases circulating myeloid and plasmacytoid DCs, as well as cDC1 and cDC2 subsets, and mobilizes hematopoietic stem/progenitor cells; it can enhance humoral and T‑cell responses to DC‑targeted vaccination. (nature.com)

Efficacy

• Healthy volunteers (Phase 1): CDX‑301 (1–75 µg/kg/day for 5–10 days) produced effective peripheral expansion of hematopoietic stem/progenitor cells and key DC subsets; this established proof of biology for downstream indications. No antitumor efficacy was evaluated in this study. (nature.com)

• Melanoma (adjuvant vaccine setting; Phase 2, randomized, open-label; NCT02129075): In patients with resected high‑risk melanoma, pretreatment with CDX‑301 before vaccination with anti‑DEC‑205–NY‑ESO‑1 plus poly‑ICLC significantly augmented immunogenicity (higher DC/innate cell expansions; increased NY‑ESO‑1 antibody and T‑cell responses) versus vaccination alone. The abstract reports 8/60 disease recurrences overall; clinical efficacy endpoints were exploratory and not the primary focus. (pubmed.ncbi.nlm.nih.gov)

• In situ immunomodulation (Phase 1, ongoing; NCT04616248): A trial combining intratumoral CDX‑301 with local radiation, CDX‑1140 (CD40 agonist) and poly‑ICLC in unresectable/metastatic solid tumors is underway; the 2024 meeting abstract details design and rationale but no response data yet. (ascopubs.org)

• Hematopoietic stem‑cell transplantation (HSCT; pilot program): Company‑reported preliminary data suggest CDX‑301 can mobilize donor HSCs as a single agent with successful engraftment in recipients; peer‑reviewed outcome data are limited and further study is needed. Preclinical work showed synergy with plerixafor for HSC mobilization. (ir.celldex.com)

Overall, published human studies demonstrate robust immune‑cell expansion and enhanced vaccine immunogenicity; definitive clinical efficacy (e.g., response rates or relapse‑free/overall survival benefits) has not yet been established.

Safety

• Healthy volunteers (Phase 1): Generally well tolerated across 5–10 days of dosing. One Grade 3 community‑acquired pneumonia occurred; otherwise no dose‑limiting toxicities or serious adverse events were reported. Common low‑grade events included injection‑site reactions and transient lymphadenopathy. No anti‑CDX‑301 antibodies were detected in that study. (nature.com)

• Melanoma vaccine study: Both regimens (with and without CDX‑301) were well tolerated; the most frequent adverse events were Grade 1–2 chills, injection‑site erythema/pain, fever, and myalgias. (ascopubs.org)

• Ongoing/other studies: Current early‑phase trials are primarily assessing safety and biologic activity; mature safety datasets in patients with cancer or HSCT settings remain limited in the public domain. (ascopubs.org)

Further reading

• Phase 1 in healthy volunteers (biologic activity and safety): Bone Marrow Transplantation 2015. (nature.com)
• ASCO abstract: Phase 2 randomized melanoma vaccine study with/without CDX‑301 (NCT02129075). (ascopubs.org)
• Mechanistic/translational report from the same melanoma trial detailing DC subset expansion and enhanced vaccine responses. (pubmed.ncbi.nlm.nih.gov)
• ASCO 2024 Trial‑in‑Progress: in situ immunomodulation with intratumoral CDX‑301 plus radiation/CD40 agonist/poly‑ICLC (NCT04616248). (ascopubs.org)
• Company materials on HSCT mobilization pilot and Phase 1 mobilization data (interpret with caution pending peer review). (ir.celldex.com)

Last updated: Oct 2025