O-0003 Phase I/II Study of 90Y-Clivatuzumab Tetraxetan (90Y-hPAM4) Combined with Gemcitabine (GEM) in Advanced Pancreatic Cancer (APC)

ABSTRACT Introduction Clivatuzumab (hPAM4) is a humanized monoclonal antibody targeting an epitope in the MUC1 antigen expressed in most pancreatic cancers. Methods Fractionated radioimmunotherapy (RAIT) with 90Y-labeled humanized mAb (90Y-hPAM4) plus Gem as first-line therapy in Stage 3-4 APC with Gem weekly x 4 with 90Y-hPAM4 on wks 2, 3 and 4. 90Y doses were escalated with Gem fixed 200 mg/m2, then Gem increased up to 1000 mg/m2, with 90Y fixed at 12 mCi/m2 for cycle 1. Results Of 100 pts, 10 withdrew early; 90 (73 stage IV) received 1-4 cycles. In Part I, 38 pts received 90Y-hPAM4 weekly x 3 at 6.5, 9, 12, or 15 mCi/m2, with the same cycle repeated 1-3 times in 13 pts. By CT-RECIST, 6 pts (16%) had PRs and 16 (42%) had stabilization (58% disease control). After cycle 1, 52% (13/25) with PET-avid images had >25% SUV reduction, and 33% (9/27) with elevated CA19-9 levels decreased by >50%. The median OS was 7.7 mo., but 11.8 mo. for retreated pts [46% (6/13) survived1 yr.], and with improved efficacy at higher 90Y doses. NCI-CTCv3 Grade 3-4 platelets or ANC developed in 20/38 (53%) after cycle 1 (all reversible to Grade 1) and in all retreated pts (irreversible in 4/9 pts at 12 or 15 mCi/m2). In Part II, 52 pts received increased Gem without evidence of improved efficacy, while 13 pts were retreated with more acceptable toxicity at lower 90Y doses of 6.5 or 9 mCi/m2. No infusion reactions occurred. Infections requiring IV antibiotics occurred at a low rate (bacteremia/sepsis, 7% febrile neutropenia, 4% ascending cholangitis, 3% pneumonia, 2% others 1%). One case of bleeding occurred, due to rectal tumor invasion. Anecdotal reports of good performance and decreased pain medication requirements require further validation. Conclusion Fractionated RAIT with 90Y-hPAM4 combined with low-dose 200 mg/m2 GEM appears promising as treatment regimen for APC. Hematologic toxicity was dose limiting. A 90Y-hPAM4 dose of 12 mCi/m2 for cycle 1 and 6.5 mCi/m2 for cycle 2 have been selected as suitable for further clinical development. PET scans are useful for assessment.