Immunomedics, Inc., a biopharmaceutical company, has reported encouraging results from the phase Ib study with clivatuzumab labeled with the radioisotope, yttrium-90 (90 Y), in patients with metastatic pancreatic cancer who had received at least 2 prior treatments.

Results from this trial were reported by Edith Mitchell, MD, from the Kimmel Cancer Center of Thomas Jefferson University in Philadelphia, Pennsylvania in an oral presentation at the European Society for Medical Oncology (ESMO) 15th World Congress on Gastrointestinal Cancer.

Clivatuzumab is a humanized antibody developed by the Company for the treatment of pancreatic cancer. It targets a specific tumour marker produced by almost all pancreatic cancers that is not usually present in  pancreatitis, normal pancreas or most other normal tissues. The Company has previously reported a median overall survival (OS) of 11.8 months in patients with newly diagnosed, untreated, advanced pancreatic cancer after receiving repeated cycles of the 90 Y-labeled antibody in combination with low-dose gemcitabine.

The current phase Ib study of clivatuzumab was undertaken in pancreatic cancer patients with two or more prior therapies. For these relapsed patients, there is no agreed standard-of-care, and options for further therapy are limited. Clivatuzumab may offer an attractive alternative, especially for those patients with adequate performance status who are unable or unwilling to accept the side effects of additional chemotherapy. The objective of this multicenter trial was to evaluate the safety, tolerability,  and evidence of efficacy of the 90 Y-labeled-clivatuzumab treatment regimen in previously-treated patients with metastatic pancreatic cancer, and to determine the contribution of low-dose gemcitabine to the treatment regimen.

A total of 58 patients were randomized to receive either 90 Y-labeled-clivatuzumab once-a-week for 3 weeks at 6.5 mCi/m2 with gemcitabine 200 mg/m2 given weekly x 4 weeks (Arm A) or 90Y-labelled-clivatuzumab alone (Arm B). This treatment cycle was repeated every 4 weeks until unacceptable toxicity, patient deterioration or patient withdrawal. Patients were followed for one year or until death. The median age of these patients was 65, with a median of 1.6 years from initial diagnosis, and a median of 3 (2-6) prior treatments.

Results from 53 patients who completed at least one treatment cycle were presented. The median overall survival (OS) for Arm A (90 Y-labelled-clivatuzumab with low-dose gemcitabine, N=27) was 119 days, a significant improvement over Arm B (90Y-labeled-clivatuzumab alone, N=26), with a median OS of 80 days (P=0.04). Furthermore, for the 23 patients who received multiple cycles of therapy, the median OS increased to 157 days in Arm A compared with 103 days in Arm B.

Survival was also related to patients’ Karnofsky Performance Status (KPS) scores at study entry, increasing from a median of 79 days for patients with 80% KPS to 119 days for patients with 90-100 per cent KPS. In contrast, increased number of prior treatments is a negative prognostic indicator for survival. The median OS decreased from 90 to 82 to 73 days for patients who received 2, 3, or 4-5 prior treatments, respectively.

“We are very encouraged with these results,  and we believe this study demonstrated the feasibility of conducting clinical trials in pancreatic cancer patients relapsed to 2 or more prior treatments. We have made the strategic decision to move forward with a phase III clinical trial, positioning clivatuzumab in this setting as a therapy for patients with advanced pancreatic cancer who have few to no treatment options,” remarked Cynthia L Sullivan, president and chief executive officer. “We have designed and vetted  our protocol with key opinion leaders and FDA, selected our clinical research organization, and plan to enroll the first patient into the phase III clinical trial by the end of this calendar year, or the beginning of 2014. Most of our clinical trial sites will be in the US, with some additional sites in the EU.”

Sullivan added, “For future clinical trials, KPS and number of prior treatments will be considered as important survival prognosticators.”

Based on the 2013 Cancer Facts and Figures report by the American Cancer Society, an estimated 45,220 Americans will be diagnosed with pancreatic cancer in 2013, making it the 10th most common cancer diagnosis among men and the 9th most common among women in the US.

Although FOLFIRINOX, the drug combination of leucovorin, fluorouracil, irinotecan, and oxaliplatin, has recently been shown to prolong  survival in patients with newly-diagnosed advanced disease, many patients could not tolerate this treatment regimen.

Immunomedics is a biopharmaceutical company primarily focused on the development of monoclonal antibody-based products for the targeted treatment of cancer, autoimmune and other serious diseases.