The combination of sorafenib plus gemcitabine and capecitabine is tolerable, but requires attenuation of sorafenib and capecitabine dosing because of the overlapping toxicity of hand-foot syndrome. Antitumor activity was observed leading to an ongoing phase II trial.
15558 Background: The de-immunized mAb J591 recognizes the extracellular domain of PSMA and was engineered to induce antibody-dependent cellular cytotoxicity (ADCC). Low-dose IL-2 results in the clonal expansion of NK cells and may enhance ADCC. We conducted a phase 2 trial to determine the efficacy and toxicity of mAb J591 plus low-dose subcutaneous (SC) IL-2 in pts with recurrent PC. Methods: 17 pts with recurrent PC (2 groups: 11 with PSA relapse only; and 6 with progressive castrate metastatic disease) received continuous low-dose SC IL-2 (1.2 x 106 IU/m2/day) daily for 8 weeks with mAb J591 (25 mg/m2 IV) weekly on weeks 4, 5 and 6 (1 cycle). Pts could receive a maximum of 3 cycles. Results: 16 evaluable pts received up to 3 cycles of therapy (16 pts, one cycle, 9 two cycles and 2 three cycles). Toxicity was mild and limited to fatigue and injection site reactions. At the end of cycle 1, PSA was stable (-50%<change in PSA<25%) in 9 of 16 patients, with PSA declines up to 34%. No PSA decline >50% was observed. A post-hoc analysis of PSA kinetics showed 5 patients had a reduction in their PSA slope of =25%; 8 of the remaining 11 patients demonstrated PSA stabilization (- 25%<change in PSA slope<25%). PSA response was most commonly observed during weeks 4–6 of the cycle correlating with mAb administration. Flow cytometric analysis of peripheral blood mononuclear cells revealed an average increase in absolute NK cell count of 107% at week 4 and 117% at the end of cycle 1. Conclusions: The combination of mAb J591 with low-dose IL-2 was well tolerated and inhibited PSA kinetics in some patients, however no responses were seen. Repetitive dosed mAb J591 is a viable strategy for use in combination with immune modulatory or other therapies in recurrent prostate cancer. No significant financial relationships to disclose.
15523 Background: A phase 1 trial of 177Lu-J591 in pts with metastatic AIPC demonstrated acceptable toxicity, excellent targeting of metastatic sites and biologic activity. Methods: Pts with progressive, metastatic AIPC receive one dose of 177Lu-J591 in two- cohorts: cohort 1 (65 mCi/m2), 15 pts; cohort 2: (70 mCi/m2), 17 pts. The primary endpoint is PSA and/or measurable disease response; secondary endpoint is toxicity. A 177Lu-J591 imaging study is done to confirm tumor targeting. Results: 21 pts (8 chemo-naive), median age 73, have been treated to date, 15 in cohort 1, 6 in cohort 2. Two pts with bone-only metastases achieved PSA declines of >50%. One had an 87% PSA decline lasting 126 days with resolution of bone pain. A 2nd pt has a PSA decline of 58% that continues without progression at 6 mo post-rx. PSA stabilization (<25% PSA rise above baseline) occurred in an additional 9 pts (43%), 7 through wk 8 (1 of whom is still under follow-up) and 2 pts through wk 12. Of 7 pts with measurable disease, 6 have had post-rx CT scans completed, 3 were stable, 3 progressed. In these pts with measurable disease, PSA was more likely to diagnose progression, with only 1 stable and 5 progressed by PSA criteria. Platelet nadir <20 x 10e9/L occurred in 6 pts, 3 of whom required platelet transfusions (mean = 2). 17/19 evaluable pts recovered normal platelet counts; the remaining 2 pts had rapidly progressive disease, 1 of whom had biopsy confirmed marrow replacement by tumor. Neutropenia </= 0.5 x 10e9/L occurred in 4 pts, 2 of whom received brief rx with growth factors. All 19 evaluable pts had normal neutrophil recovery. No significant drug-related non-hematologic toxicity has occurred. Targeting of known sites of PC metastases has been observed in all pts. Conclusions: Single dose 177Lu-J591 demonstrates anti-tumor activity in pts with progressive, metastatic AIPC with reversible myelosuppression. Accrual is continuing. [Table: see text]
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