Purpose: KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. This first-in-human phase I study evaluated the safety/tolerability, pharmacokinetics, preliminary efficacy, and potential predictive biomarker activity of KN026 administered as monotherapy to patients with HER2-positive metastatic breast cancer (MBC). Patients and Methods: Female patients with HER2-positive MBC who had progressed on prior anti HER2 therapies received intravenous KN026 monotherapy at 5 mg/kg (once weekly), 10 mg/kg (once weekly), 20 mg/kg (once every 2 weeks), or 30 mg/kg (once every 3 weeks). Dose escalation was guided by a “3+3” dose escalation rule followed by dose expansion. Results: Sixty-three patients were enrolled. The most common treatment-related adverse events (TRAE) were pyrexia (23.8%), diarrhea (22.2%), aspartate aminotransferase increased (22.2%), alanine aminotransferase increased (22.2%). Only 4 patients reported grade 3 TRAEs. Results from exposure-response analysis supported the selection of the recommended phase II doses at 20 mg/kg once every 2 weeks or 30 mg/kg once every 3 weeks, which had objective response rates (ORR) of 28.1% and median progression-free survival (PFS) of 6.8 months (95% confidence interval: 4.2–8.3) in 57 patients. Translational research in 20 HER2-amplified patients further confirmed that co-amplification (vs. no co-amplification) of CDK12 was a promising biomarker in predicting better response to KN026 (ORR of 50% vs. 0% and median PFS of 8.2 vs. 2.7 months, P = 0.05 and 0.04, respectively). Conclusions: KN026, a HER2 bispecific antibody, was well tolerated and achieved comparable efficacy as trastuzumab and pertuzumab doublet even in the more heavily pretreated patients. Co-amplification of HER2/CDK12 may define patients who benefit more from KN026.

PurposeThe aim of this study was to investigate the role of circulating tumor cells (CTCs) in assessing and predicting tumor response to neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC).MethodsA total of 115 patients with T3-4 and/or N+ rectal cancer were enrolled. All patients received neoadjuvant CRT followed by radical surgery after 6-8 weeks. The pathological results after surgery were evaluated according to tumor regression grade (TRG) classification.ResultsBased on TRG score, patients were classified as responders (TRG3-4) and non-responders (TRG0-2). The baseline CTC counts of responders were significantly higher than those of non-responders (44.50±11.94 vs. 37.67±15.45, P=0.012). By contrast, the post-CRT CTC counts of responders were significantly lower than those of non-responders (3.61±2.90 vs. 12.08±7.40, P<0.001). According to ROC analysis, Δ%CTC (percentage difference in CTC counts between baseline and post-CRT) was identified as the stronger predictor to discriminate responders from non-responders (AUC: 0.860). The results of multivariate analysis also indicated that post-CRT CTC counts and Δ%CTC were significantly and independently associated with tumor response to CRT.ConclusionsThe detection of CTCs is a powerful and promising tool for evaluating and predicting responses to neoadjuvant CRT in LARC patients.

Differences in the SUV/metabolic area with 18F-fluorodeoxyglucose (18(F) -FDG) PET/CT have the potential to predict a response to preoperative CRT for rectal cancer.