New data from two clinical trials suggest that nadunolimab, an antibody-based therapy, may offer a significant benefit to cancer patients who have progressed after treatment with pembrolizumab, a widely used PD-1 inhibitor. The findings, involving 55 patients across various cancer types, highlight nadunolimab's potential to target immunosuppressive cells within the tumor microenvironment.
The data, released by Cantargia AB, were derived from the CANFOUR and CIRIFOUR trials. These results are scheduled for presentation at the ESMO Congress 2024 in Barcelona.
CANFOUR Trial: Nadunolimab in NSCLC
The CANFOUR trial investigated nadunolimab in combination with platinum doublet chemotherapy in 40 patients with first- or second-line non-small cell lung cancer (NSCLC). Notably, 17 of the second-line patients had previously been treated with pembrolizumab. The second-line patients demonstrated a higher objective response rate (ORR) of 72% compared to 41% in first-line patients. Additionally, second-line patients showed a median progression-free survival (PFS) of 7.6 months versus 6.7 months in first-line, and a median overall survival (OS) of 15.7 months versus 11.5 months (p = 0.038).
In a subset of second-line non-squamous NSCLC patients (n=12), the ORR was 92%, with a median OS of 28.9 months and PFS of 13.0 months, including two complete responders. Biopsy analyses indicated that second-line patients had a higher number of IL1RAP-positive immune cells, CD163+ macrophages, CD56+ NK cells, and CD8+ T cells in the tumor at baseline, suggesting nadunolimab's mechanism involves targeting tumor-promoting cells within the tumor microenvironment (TME).
CIRIFOUR Trial: Nadunolimab with Pembrolizumab
The CIRIFOUR trial evaluated nadunolimab in combination with pembrolizumab in 15 heavily pretreated patients who had previously progressed on pembrolizumab monotherapy or combination treatments. The patient cohort included nine with head and neck cancer, five with NSCLC, and one with melanoma. The median survival was 19.7 months, and the disease control rate was 60%. Similar to the CANFOUR trial, the most pronounced benefits were observed in patients with a specific profile of immune and immunosuppressive cells in the TME. The combination therapy was reportedly well-tolerated.
Implications and Future Directions
Göran Forsberg, CEO of Cantargia, stated, "The new data, from two separate clinical trials, show a long median survival in nadunolimab treated patients after previous therapy using pembrolizumab. These patients have a tumor microenvironment containing immune suppressive cells that can be targeted with nadunolimab. These findings clearly support additional studies as the vast number of patients who progress on immunotherapy have limited treatment options."
The findings suggest that nadunolimab may offer a valuable treatment option for patients who have developed resistance to PD-1 inhibitors. Further research is warranted to fully elucidate the mechanisms of action and to identify predictive biomarkers for patient selection.
