Approximately 20% of breast cancers harbor human epidermal growth factor receptor 2 (HER2/ERBB2) overexpression or amplification. KN026, a novel HER2 bispecific antibody, has been shown to overcome resistance to HER2 target therapies in preclinical models. Zhang and colleagues conducted a phase I trial of KN026 in patients with HER2-positive metastatic breast cancer who had progressed on prior anti-HER2 therapies. KN026 was well tolerated, and treatment led to an objective response rate of 28.1%. Furthermore, the authors associated CDK12 co-amplification with an improved response to KN026, supporting further assessment of this potential biomarker. Although these results are interesting, further clinical trials of this novel bispecific antibody are warranted.Metastasis is a common occurrence in patients with osteosarcoma. Although current therapeutics have shown limited ability to reduce metastasis, CCR2+ monocytes have emerged as an actionable target for the prevention of lung metastasis. Regan and colleagues conducted a clinical trial in pet dogs with spontaneous advanced metastatic osteosarcoma to assess high-dose losartan, an angiotensin receptor inhibitor, in this context. In combination with the kinase inhibitor toceranib, losartan inhibited the CCL2-CCR2 pathway, was well tolerated and led to a clinical benefit rate of 50%. These results support further clinical study of losartan, especially human clinical trials.Although immunotherapy has provided a benefit to many patients, predictive biomarkers are still needed to more effectively guide treatment in patients with advanced renal cell carcinoma (RCC). To identify potential biomarkers in patients with advanced RCC treated with avelumab plus axitinib or sunitinib, Bilen and colleagues conducted a post hoc analysis of data from the phase 3 JAVELIN Renal 101 trial. The authors found that a low neutrophil-to-lymphocyte ratio (NLR) was associated with longer progression-free survival, overall survival, and objective response rate. These results support the continued development of NLR as a predictive biomarker for immunotherapy in patients with advanced RCC.Prior studies have shown that cabozantinib, an inhibitor of VEGFRs and additional tyrosine kinases, is effective for the treatment of metastatic clear cell renal cell carcinoma (mccRCC). However, it is unclear whether the mechanism of this agent is via its targeting of VEGFR or another target. To address this question, Denize and colleagues assessed angiogenesis markers in patients treated with cabozantinib or everolimus as part of the METEOR trial. Microvascular density and mast cell density, both markers of angiogenesis, were both associated with longer progression-free survival. Furthermore, patients treated with cabozantinib had improved progression-free survival, overall survival, and objective response rate compared with those treated with everolimus; importantly, these results were not dependent on levels of microvascular density or mast cell density. These results support the activity of cabozantinib in patients with mccRCC and suggest that VEGFR-independent effects may be part of the mechanism of this agent.