Juan C Osorio: First-in-Human Trial of Intratumoral CD40 Agonist 2141-V11 in Metastatic Cancer
Juan C Osorio, Assistant Attending at Memorial Sloan Kettering Cancer Center and Director of Clinical Operations and Translational Immunology at The Rockefeller University, shared a post on X:
“Thrilled to share our new publication on the first-in-human phase 1 trial of intratumoral Fc-engineered CD40 agonistic antibody 2141-V11 in metastatic cancer. Over 10 years of preclinical work led to this moment, made possible by an amazing team!
CD40 agonist have shown promise but mostly failed due to toxicity and weak activity. We previously showed that 2141-V11, Fc-engineered for increased FcγRIIB binding, leads to superior antitumor activity and reduced toxicity in preclinical models, paving the way for this trial.
Led by David Knorr, our phase trial (12 pts) showed that IT 2141-V11 was safe, and in two patients, led to sustained CR in both injected and distant, non-injected lesions, validating over a decade of preclinical findings using our humanized mouse models!
Another unexpected discovery was that IT 2141-V11 not only was safe but appear to trigger tertiary lymphoid structures (TLS) formation, which not only supports intratumoral administration as a safe approach but also the most effective way to promote optimal immune activation.
Elegant preclinical work by Polina Weitzenfeld confirmed that 2142-V11 induces TLS formation across tumor models & drives antitumor responses even without lymph node trafficking, opening tons of mechanistic questions and exciting avenues for subsequent combination approaches!
This first study has inspired several ongoing phase-2 studies nationwide (glioblastoma, bladder and prostate cancer). Early data from these studies look promising -Stay tuned! We’re incredibly grateful to the patients, families, philanthropic/federal support to make this possible.”
This first study has inspired several ongoing phase-2 studies nationwide (glioblastoma, bladder and prostate cancer). Early data from these studies look promising -Stay tuned! We’re incredibly grateful to the patients, families, philanthropic/federal support to make this possible.”
Title: Fc-optimized CD40 agonistic antibody elicits tertiary lymphoid structure formation and systemic antitumor immunity in metastatic cancer
Authors: Juan C. Osorio, David A. Knorr, Polina Weitzenfeld, Lucas Blanchard, Ning Yao, Maria Baez, Carlo Sevilla, Meghan DiLillo, Jahan Rahman, Ved P. Sharma, Jacqueline Bromberg, Michael A. Postow, Charlotte Ariyan, Mark E. Robson, Jeffrey V. Ravetch
Read The Full Article at Cancer Cell.
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