A Cytokine Working Group (CWG) 3-arm phase II trial of gp100 (209-2M) peptide + high dose (HD) Interleukin-2 (IL-2) in HLA-A2+ (A2+) advanced melanoma patients (pts).

7504 Background: HD IL-2 induces responses in 15% of advanced melanoma pts, of which 5-8% are durable CRs. The A2-restricted gp100 peptide (209-2M), is able to induce T cell responses in vivo, but is inactive as a single agent. The NCI combined 209-2M with HD IL-2 for a 42% (13/31) response rate (RR),(Nat Med,1998). We studied the vaccine in a randomized phase II trial, involving 3 different IL-2 schedules. The different schedules were based on the NCI experience.,All patients received 209-2M, subcutaneously, weeks (wks) 1, 4, 7, 10 and HD IL-2 (0.6MU/kg/dose IVP q 8hrs x 14) on wk 1 and 3 (arm 1), wk 7 and 9 (arm 2), or wk 1, 4, 7, 10 (arm 3) starting 24 hrs post 209-2M. The treatment (Rx) was repeated up to 2x at 12 wk intervals in patients with CR, PR, or SD. Initial preferential assignment was given to arm 3 (Proc ASCO abst 1423, 2001) with subsequent randomized assignment to arms 1 and 2.,131 A2+ pts (arm 1=46 arm 2=43 arm 3=42) were enrolled from 9/1998 to 11/2003. 117 are fully evaluable. Groups had similar characteristics. Overall, M:F 60%:40%, median age 50(20-76), PS 0:1 84%:16%, High LDH 27%, prior adjuvant IFN 36%, prior chemotherapy 14%. 14 pts (12%) (9 from arm 2) did not receive any IL-2 due to disease progression. Median # IL-2 doses over 1st course relative to a maximum were 20/28, 20/28, and 34/56 in arms 1, 2, and 3, respectively. 3 pts died on protocol due to disease progression. With a median f/u of 3.5 yrs, the overall RR is 14.5%, (17/117) with 19% arm 1, 12.5% arm 2, and 8.8% arm 3. Responses included 9 CR (8%) and 8 PR (7%). 20 pts (17%) remain progression-free, 12 on arm 1 (28%). 30 pts (26%) remain alive at 12-62+ mos.,None of the schedules of 209-2M + HD IL-2 produced better activity than expected with IL-2 alone. Arm 3 with greater dose intensity and arm 2 with 6 wks of 209-2M prior to starting IL-2 were particularly disappointing. Results support the early initiation of standard HD IL-2 after the diagnosis of advanced melanoma. Lymphocytes are available pre-Rx and at 12 wks on a large # of pts. These will be analyzed for immune changes and these findings will be presented along with the clinical results. [Table: see text].