Activity of fractionated radioimmunotherapy with clivatuzumab tetraxetan combined with low-dose gemcitabine (Gem) in advanced pancreatic cancer (APC)

240 Background: The90Y-labeled anti-mucin humanized mAb, clivatuzumab tetraxetan (90Y-hPAM4), is in clinical development in APC. A phase I/II trial of 90Y-hPAM4 with low-dose radiosensitizing Gem has now concluded 90Y-dose escalation. Methods: Pts with untreated, inoperable, stage 3-4 APC received 200 mg/m2 Gem once-weekly x 4 with 90Y-hPAM4 on wks 2-4, and with 90Y escalated in cohorts by 3+3 design. Tumor responses were assessed by CT, FDG/PET and serum CA19.9, with cycles repeated until progression or unacceptable toxicity. Results: Of 42 pts (40-87 yrs, ECOG PS 0-1, 36 stage 4), 4 withdrew early while 38 received weekly x 3 90Y doses of 6.5 (N=4), 9 (N=12), 12 (N=17) and 15 (N=5) mCi/m2. Treatment was well-tolerated with few non-hematologic side-effects, including 13 pts retreated with 1-3 additional cycles. CTCv3 grade 3-4 plts or ANC developed in 21/38 (55%) pts after cycle 1 and all (100%) retreated pts after last cycle. Escalation reached limits on radiation doses to the marrow, but hematologic suppression was reversible without major infections or bleeding events, except for 3 pts after repeated cycles, one with extensive marrow tumor infiltration. By CT, the overall disease control rate was 55%, including 6 pts (16%) with partial responses (PRs) by RECIST criteria and 15 pts (39%) with stabilization as best response. After cycle 1, 43% (10/23) improved by PET studies (negative or >25% reduced uptake), and 36% (9/25) with elevated CA19.9 levels had >50 decreases. With 26% (10/38) of pts still in follow-up, 55% (21/38) have now achieved survival of ≥ 6 months [18% (7/38) ≥ 1 yr]. Treatment outcome may increase with 90Y dose, since pts treated at 3 x ≥12 mCi/m2 vs ≤9 mCi/m2 had 19% vs 6% PRs by CT, 47% vs 22% CA19.9 decreases, 63% vs 25% PET improvement, and 64% vs. 44% survival ≥ 6 months. Anecdotally, PS and pain level improved, which needs validation. Updated survival will be presented at the meeting. Conclusions: Fractionated 90Y-hPAM4 plus low-dose Gem showed encouraging therapeutic activity with manageable hematological toxicity. The 12-mCi/m2 dose level was selected for continued dose exploration now underway, involving standard Gem doses and adding maintenance Gem. [Table: see text]