Induction of immune responses and clinical activity in a phase II trial of IDM-2101, a 10-epitope CTL vaccine, in metastatic NSCLC patients.
8057 Background: IDM-2101 is a 10-peptide vaccine designed to induce multi-specific CTL responses against MHC class I epitopes of CEA, p53, HER-2/neu and MAGE 2/3. Seven epitopes are modified for enhanced MHC binding or heteroclitic T-cell activation and 2 epitopes are native wild-type (WT) sequences. Also included is the class II helper epitope PADRE. We report here immune responses and clinical activity from a Phase 2 trial of IDM-2101. METHODS: 68 HLA-A2+ good performance patients (pts) with Stage IIIB/IV or recurrent NSCLC were enrolled. Patients were required to have a tumor volume <125 cm2. Pts received 6 induction doses (0.5 mg/epitope) q3 wks followed by maintenance treatments at 2-3 month intervals. 63 pts were treated with one or more doses. 72 HLA-A2 negative pts who were otherwise eligible were retrospectively selected as relevant controls. Endpoints included survival, clinical responses and induction of immune responses. CTL responses in peripheral blood MNC were measured, at predefined time points, after a 10 day in vitro stimulation with peptide followed by an IFNγ ELISPOT assay. RESULTS: 30 of 33 available pts (91%) that were monitored for CTL showed positive responses to 1 or more epitopes and 21 of 33 pts (64%) responded to at least 3 epitopes. All 9 vaccine epitopes were immunogenic in at least 1 patient. CTL responses were detected in 3 of 4 pts tested at 12 months. T helper-cell responses against PADRE measured with a direct IFNγ ELISPOT assay were observed in 18 of the 33 pts (55%) tested. Toxicities attributable to vaccine were mild and consisted mostly of injection site reactions. Clinical responses included 1 CR, 1 PR and SD of ≥3 months in 54 of 63 pts (86%). 14 pts completed 2 years of dosing and remain without evidence of progression. Interim analysis of one-year survival in IDM-2101 treated pts was 60%, compared to 49% in the HLA-A2 negative group and median survival for treated pts was 17.3 months compared to 12.0 months for pts in the HLA-A2 negative group. A trend toward longer survival was observed in pts who responded to more epitopes. CONCLUSIONS: IDM-2101 was well- tolerated, induced broadly-specific CTL responses and may provide a survival benefit in metastatic NSCLC patients. [Table: see text].
Barve, M; Bender, J; Pappen, B; Ishioka, G; Morse, MA; Greco, FA; McCune, D; Steis, R; Khong, H; Nemunaitis, JJ; Mary Crowley Medical Research Trial Network,
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