Immunomedics, a biopharma firm focused on developing monoclonal antibodies to treat cancer and other serious diseases, has reported that a new blood assay using the company's proprietary humanized antibody, clivatuzumab or PAM4, predicted a partial response in an initial set of patients treated with a combination of the antibody labeled with yttrium-90 (Y-90) and gemcitabine.
Immunomedics had recently developed a new serum-based enzyme immunoassay (ELISA) for early diagnosis of pancreatic cancer, employing clivatuzumab that has a sensitivity of 62% for detecting stage-1 pancreatic cancer (disease confined to pancreas), 86% for stage 2 disease, and 91% for stage 3/4 (local and distant spread) cancers.
Immunomedics had reported an overall response rate of 68% with 5 patients having a partial response (PR), 10 with stable disease (SD) and 7 with progressive disease (POD). From the initial group of 22 patients, 17 were evaluable as having both baseline and follow-up sera available for PAM4 testing, of which 4 were PR, 11 patients with SD and 2 patients with POD. Notably, 1 patient was negative for PAM4 in the circulation and excluded from the evaluation.
The PAM4 ELISA correctly predicted 4 of 4 PRs. Four of 9 patients with SD were also predicted to have had a PR rather than an SD. However, it is noted that one of the SD patients had a 29% decrease in tumor size which is just under the 30% criteria under RECIST to qualify as a PR. Overall, the sensitivity for detection of a PR was 100% with a specificity of 68%. Importantly, neither of the patients with POD was falsely recognized as PR.
Separately, in a study to be reported later, the effects of adding an antibody-drug conjugate that targets pancreatic cancer (hRS7-SN-38) to Y-90 labeled Clivatuzumab tetraxetan were investigated in a mouse model of human pancreatic cancer. Results showed that the combination produced more robust objective response than each agent alone.
Immunomedics said that in particular, all animals receiving Y90-clivatuzumab at the maximum tolerated dose and hRS7-SN-38 achieved a tumor-free state within 4 weeks, while other animals continued to have evidence of persistent disease. These studies provide the first evidence that combined radioimmunotherapy and antibody-drug conjugate can enhance efficacy at safe doses.
Cynthia Sullivan, president and CEO, said: “We have now demonstrated that the blood assay for PAM4-protein can not only detect early-stage pancreatic cancer, as has recently been reported by us, but may also predict a lack of response to therapy or an early relapse. As a result, we believe we may be one step closer to offering an individualized approach for the management of this lethal disease.
“Although these results are based on a small number of patients, the trend encourages us to expand such studies to evaluate whether this new bioassay for pancreatic cancer continues to be predictive of response to diverse therapies.”