The PANcreatic Cancer RadioImmunotherapy Trial-1 (PANCRIT-1) starts its patient accrual phase. This trial is a double-blind, randomized study and will enroll approximately 440 patients with metastatic pancreatic cancer. A majority of patients will be recruited at clinical trial sites across the United States, with additional sites in Canada, Europe and Israel participating. Eligible patients will be randomized 2 to 1 to the treatment arm of 3 doses of 90Y-clivatuzumab tetraxetan (Immunomedics, Inc.) plus 4 doses of gemcitabine at 200 mg/m2 per cycle or placebo plus low-dose gemcitabine. All participating patients will receive best supportive care. Treatments are administered during the initial 4 weeks of each 7-week cycle, and may be repeated up to a maximum of 6 cycles.

Each of the patients to be enrolled has metastatic pancreatic cancer who have received at least two prior therapies, one of which must have been a gemcitabine-containing regimen. The primary endpoint of this study is overall survival or OS.

Clivatuzumab tetraxetan could become the first antibody-directed radiation therapy approved to treat patients with solid tumors.

According to the American Cancer Society, an estimated 45,220 Americans were 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 U.S. It is, however, the fourth leading cause of cancer death among both men and women nationwide, with approximately 38,460 deaths expected, or about 7% of all cancer deaths.


Approved therapies
Currently, only 2% percent of patients diagnosed with pancreatic cancer are alive 5 years later.Gemcitabine (Gemzar?;Eli Lilly and Company) alone or in combination with Erlotinib (Tarceva?; OSI Pharmaceuticals/Astellas Pharma and Genentech) or protein-bound paclitaxel (Abraxane?; Celgene) are the only front-line treatments approved by the U.S. Food and Drug Administration (U.S. FDA) for patients with late-stage pancreatic cancer. There are no FDA-approvedtherapies for patients that relapse and there are only a few treatment options available.

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In a recently completed Phase Ib clinical trial in the same patient population with relapsed pancreatic cancer, the combination of 90Y-clivatuzumab tetraxetan and low-dose gemcitabine produced a median OS of 4.0 months (6 of 27 subjects were alive 9 months after first dose) with a manageable safety profile. That was statistically significant (p = 0.021) compared to the median OS of 2.8 months when patients were treated with 90Y-clivatuzumab tetraxetan alone.

Additionally, there were 2 partial responders in the combination arm. More importantly, the rapid enrollment of the Phase Ib study demonstrated an unmet medical need for treatment options for patients in this late-stage setting.

?If the results from the Phase Ib study are confirmed by the PANCRIT-1 trial, clivatuzumabtetraxetan could become the first antibody-directed radiation therapy approved to treat patientswith solid tumors. We plan to complete patient accrual in the first half of 2015,? noted Cynthia L. Sullivan, President and Chief Executive Officer of New Jersey-based Immunimedics.

Unique approach
Clivatuzumab tetraxetan contains a humanized, highly specific antibody that targets a mucin antigen found on pancreatic cancer cells, and is conjugated to a linker that facilitates complexing with radiometals. This mucin has been found by tissue staining to be present on about 85% ofpancreatic cancers but is not found on normal pancreas or tissue from patients with pancreatitis.

When the antibody-linker complex is radiolabeled with yttrium-90, this enables delivery of highintensity, deep penetrating radiation directly to the pancreatic tumor cells and the addition ofgemcitabine acts as a radiosensitizer to increase the anti-tumor activity. 90Y-clivatuzumabtetraxetan has received Orphan Drug designation in both the U.S. and Europe, and fast trackdesignation in the U.S. for the treatment of patients with pancreatic cancer.

In earlier clinical trials, 90Y-clivatuzumab tetraxetan has produced encouraging results incombination with gemcitabine in newly-diagnosed pancreatic cancer patients or alone in therelapsed population.[1][2]

For more information
[1] Ocean A.J., Pennington K.L., Guarino M.J. et al. Fractionated radioimmunotherapy with 90Yclivatuzumab
tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer: A
Phase I trial. Cancer. 2012 Nov 15;118(22):5497-506. doi: 10.1002/cncr.27592. Epub 2012 [Article] [PubMed]
May 8.
[2] Gulec S.A., Cohen S.J., Pennington K.L. et al. Treatment of advanced pancreatic carcinoma
with 90Y-clivatuzumab tetraxetan: a Phase I single-dose escalation trial. Clin Cancer Res.
2011 Jun 15;17(12):4091-100. doi: 10.1158/1078-0432.CCR-10-2579. Epub 2011 Apr 28.[Article][PubMed]

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