Conclusions
NSCLC, pembrolizumab, HNSCC, uterine cancer, chemo-resistant solid tumors, SD, malignancies, tumors
SOLID TUMORS, MALIGNANCIES, CERVICAL CANCER, NSCLC, TUMOR GROWTH, TUMORS
This first-in-human study of NEO-201 in solid tumors demonstrated that NEO-201 was well-tolerated and the RP2D was established at 1.5 mg/kg. Exploratory studies in serum suggested a correlation between maintenance of SD and lower baseline levels of soluble serum MICA, while serum levels of CEACAM-5 and CEACAM-6 were not related to the outcome of the treatment. In this study we also reported the ability of NEO-201 to bind to circulating Tregs. The reduction in circulating Tregs after NEO-201 infusion in patients with SD was one of the rationales to combine NEO-201 with pembrolizumab in the ongoing phase II clinical trial in adults with chemo-resistant solid tumors [Patients with malignancies for which checkpoint inhibitors are clinically indicated, including NSCLC, HNSCC, uterine cancer, and cervical cancer, often do not respond to initial treatment and eventually become resistant to many therapies. Resistance to immunotherapy is a great challenge from a therapeutic standpoint and necessitates the development of novel approaches to circumvent resistance, including combination therapies. Combining NEO-201 with pembrolizumab in our ongoing phase II clinical trial could be a promising strategy to enhance immune system mediated anti-tumor activity for two reasons: 1) NEO-201 may overcome resistance to checkpoint inhibitors, by depleting Tregs involved in the immunosuppression of immune cells that play a role in the control of tumor growth; 2) NEO-201 can kill via ADCC and/or CDC, tumors expressing its target antigen in subjects for whom pembrolizumab is currently indicated.