SHR-1701 Plus Famitinib Shows Promise in Advanced Biliary Tract and Pancreatic Cancer
核心洞察
Combination therapy with SHR-1701 and famitinib demonstrates encouraging objective response rates in biliary tract cancer (搜索) (BTC) and pancreatic ductal adenocarcinoma (搜索) (PDAC) patients.
The median overall survival (OS) was 16.0 months for BTC patients and 5.3 months for PDAC patients, indicating a potential survival benefit.
Responders exhibited upregulation of immune-related pathways, while non-responders showed enrichment of metabolic pathways, suggesting distinct mechanisms of treatment response.
A recent study published in Nature explores the efficacy and safety of combining SHR-1701, a bifunctional fusion protein, with famitinib, a tyrosine kinase (搜索) inhibitor, in patients with advanced biliary tract cancer (搜索) (BTC) and pancreatic ductal adenocarcinoma (搜索) (PDAC). The study, enrolling 51 patients, reveals promising objective response rates and survival outcomes, particularly in BTC, offering a potential new treatment avenue for these difficult-to-treat cancers.
Clinical Outcomes in BTC and PDAC
The trial included 27 patients with BTC and 24 patients with PDAC, all of whom received the combination therapy. Efficacy was evaluated in 25 BTC patients and 20 PDAC patients. The objective response rate (ORR) in the BTC cohort was 28.0% (95% CI: 12.1-49.4), including 2 complete responses (CR) and 5 partial responses (PR). The PDAC cohort showed an ORR of 15.0% (95% CI: 3.2-37.9), with 2 CRs and one PR. The disease control rate (DCR) was 80.0% for BTC and 60.0% for PDAC.
The median duration of response (mDoR) in BTC patients was 7.6 months (95% CI: 2.2-13.0 months). The median progression-free survival (mPFS) was 5.1 months (95% CI: 2.6-7.6 months), and the median overall survival (mOS) was 16.0 months (95% CI: 6.1-NE). In the PDAC group, the mPFS was 2.1 months (95% CI: 0.7-3.5 months), and the mOS was 5.3 months (95% CI: 4.0-6.5 months).
Safety and Tolerability
The combination therapy's safety profile was also assessed. The majority of patients (88.2%) experienced at least one treatment-related adverse event (TRAE). The most common TRAEs of any grade were proteinuria (47.1%), anemia (39.2%), and positive urinary occult blood (31.4%). Grade 3 or 4 TRAEs occurred in 29.4% of patients, with anemia (13.7%) and hypertension (7.8%) being the most frequent. Immune-related adverse events were observed in 31.4% of cases, with rash (23.5%) and hypothyroidism (13.7%) being the most common. TRAEs led to treatment interruption in some patients, but only 7.8% discontinued treatment due to adverse events.
Biomarker Analysis and Immune Profiling
Comprehensive biomarker analysis revealed distinct gene expression patterns between BTC and PDAC patients. Responders exhibited upregulation of immune-related pathways, including leukocyte adhesion, migration, and activation, as well as T cell differentiation and activation. Non-responders, on the other hand, showed enrichment of metabolic pathways, such as amino acid metabolism and catabolism.
Further analysis identified an immune/metabolism (I/M) score based on the pretreatment expression of six genes. This score demonstrated promising predictive power for immunotherapy efficacy, with higher scores associated with better treatment response and prolonged overall survival. Multiplex immunofluorescence confirmed the presence of tertiary lymphoid structures (TLS) in responders, indicating an active immune microenvironment.
Implications for Future Treatment Strategies
These findings suggest that the combination of SHR-1701 and famitinib could be a valuable treatment option for patients with advanced BTC and PDAC. The identification of the I/M score as a potential predictive biomarker may help to personalize treatment strategies and select patients most likely to benefit from this combination therapy. Further research is warranted to validate these findings in larger clinical trials and to explore the underlying mechanisms driving the observed treatment responses.