varlilumab (CDX 1127)

The combinations of atezolizumab and varlilumab with/without cobimetinib were safe but neither meaningfully improved outcomes in BTC treated in the later lines. Correlative tissue studies validated preclinical work that MEK inhibition increases CD8+TILs.

P2, N=43, Active, not recruiting, Annick Desjardins, MD | Trial completion date: Mar 2026 --> Mar 2027 | Trial primary completion date: Mar 2026 --> Mar 2027

Immune checkpoint receptors (LAG3, CD27) connect via PPI intermediates to Ca2+ and K+ channels, targetable by relatlimab (FDA-approved) and varlilumab (Phase 2). This work maps previously unknown links between CRC driver genes and ion channel regulation, with the ataluren-RPS21-KCNQ2 axis ready for pharmacological testing.

No synergistic toxicity was observed with combination treatment. Similar durability in immunogenicity was found with or without varlilumab. Depletion of circulating CD4+ T cells with varlilumab may have abrogated benefits of inducing tumor-cognate CD4+ T cells with vaccination. Induction of memory responses supports further work to optimize shared antigen vaccines in combination with other immunotherapies.

P1, N=16, Terminated, Rutgers, The State University of New Jersey | Active, not recruiting --> Terminated; accrual goal met

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

Rituximab and varlilumab show modest activity. However, CD27 agonist antibodies may elicit meaningful anti-tumor responses when tumors express sufficient intratumoral targets and exhibit existing immune priming.

Our hypothesis was immune suppression after pediatric thermal injury is reversible ex-vivo using immunomodulators recombinant human granulocyte macrophage-colony stimulating factor (GM-CSF) and varlilumab (CD27-agonist)...Samples co-incubated with GM-CSF significantly increased ex-vivo LPS-induced TNFα while samples containing CD27 increased PHA-induced IL-10 production capacity, in the first 72 h, compared to samples that did not receive immunomodulators. The results of our study identified key markers to discover those most at risk for development of NI and provided early evidence of immunomodulators that may enhance immune function early after pediatric burn injury.

P2, N=43, Active, not recruiting, Annick Desjardins, MD | Trial completion date: Mar 2025 --> Mar 2026 | Trial primary completion date: Mar 2025 --> Mar 2026

P1/2, N=26, Completed, University Hospital Southampton NHS Foundation Trust | Active, not recruiting --> Completed | Phase classification: P2a --> P1/2 | Trial completion date: Mar 2024 --> Aug 2024

P2, N=54, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2024 --> Oct 2025

Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.