First-in-Human Study of ⁸⁹Zr-DFO-HuMab-5B1 (MVT-2163) PET/CT imaging with and without HuMab-5B1 (MVT-5873) in patients with pancreatic cancer and other CA 19-9 positive malignancies

Objectives: Immuno-PET with ⁸⁹Zr-labeled antibodies is a promising approach for detection, staging and characterization of malignant tumors. The monoclonal antibody HuMab-5B1 potently binds on the CA 19-9 antigen expressed on various malignancies including pancreatic tumors. Although the CA 19-9 antigen is present in the circulation, its concentration in tumor is orders of magnitude higher and leads to accumulation of HuMab-5B1 in mice bearing CA19-9 expressing tumors. The aim of this ongoing first in human study was to obtain data on the safety and feasibility of ⁸⁹Zr-DFO-HuMab-5B1 to image pancreatic tumors and other CA 19-9 positive malignancies (NCT02687230).

Methods: 9 patients with CA 19-9 positive metastatic malignancies (8 pancreatic, 1 of unknown origin with peritoneal carcinomatosis) were injected with a mean of 171 +/- 8 MBq ⁸⁹Zr-DFO-HuMab-5B1 (antibody mass 3 mg). Cohorts of 3 patients received escalating doses of unlabeled HuMab-5B1 (MVT-5873) (0, 17, and 47 mg) within 2 h prior to injection of the radiolabeled HuMab-5B1 (MVT-2163) for a total antibody mass of 3, 20 and 50 mg. All patients underwent a total of 4 whole-body PET/CT scans (the day of injection, day 2, day 4 ±1, and day 7 ±1). A diagnostic CT scan of the chest, abdomen and pelvis was performed in all patients within 4 weeks prior to injection of ⁸⁹Zr-DFO-HuMab-5B1 and was used to correlate findings on of ⁸⁹Zr-DFO-HuMab-5B PET/CT. Uptake of ⁸⁹Zr-DFO-HuMab-5B1 in tumor lesions was quantified by maximum standardized uptake values normalized to body weight (SUVmax).

Results: Injection of the antibodies was well tolerated at all dose levels. 5 patients had no side effects and 4 patients demonstrated chills after injection (3 CTCAE grade 1 and 1 grade 2). Focal radiotracer uptake was observed in lesions starting from day 2 and continuously increased to day 7. ⁸⁹Zr-DFO-HuMab-5B1 accumulated in known local recurrences, lung, lymph node, bone and peritoneal metastases. In addition, we observed intense uptake in subcentimeter retroperitoneal and mesenteric nodes that were normal by CT criteria. Uptake of ⁸⁹Zr-DFO-HuMab-5B1 was analyzed for a total of 52 lesions. The average SUVmax (SEM) at days 1,2,4 and 7 was 2.9 (0.16), 6.3 (0.67), 10.1 (1.29), and 14.4 (1.8), respectively. Tumor visualization was best on day 7 with a tumor-to background (mesenteric fat) ratio of 22.0 (3.0). The highest tracer uptake was seen in lymph nodes (SUV up 57.2). Figure 1 shows a fused PET/CT image on day 7 with uptake in nodular peritoneal carcinomatosis (small arrows) and a retrocaval node (large arrow). Average SUVmax of lesions decreased with escalating HuMab-5B1 masses (average SUVmax 22.6, 10.6 and 8.6 for cohorts 1, 2, 3, respectively, Kruskal-Wallis test, p = 0.007). CA 19-9 values varied from 14-6,277 U/ml (average: 1788 U/ml) and showed no correlation with SUVs.

Conclusion: ⁸⁹Zr-DFO-HuMab-5B1 PET/CT imaging with HuMab-5B1 is safe and demonstrates promising results for the detection of CA 19-9 positive malignancies. Further studies correlating imaging findings with histopathology are warranted to assess the accuracy of this imaging modality for detection of CA19-9 positive malignancies. Research Support: The clinical study was funded partly by the David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center. $$graphic_85017D82-A209-4243-A374-D23F153E67F1$$