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I. Pastan
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O22 - Mesothelioma III (ID 122)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Mesothelioma
- Presentations: 1
- Moderators:P. Baas, R. Gaafar
- Coordinates: 10/29/2013, 16:15 - 17:45, Bayside Gallery A, Level 1
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O22.03 - Durable cancer regressions in chemotherapy refractory mesothelioma patients with the anti-mesothelin immunotoxin SS1P and host immune depletion with pentostatin (P) and cyclophosphamide (C) (ID 1630)
16:35 - 16:45 | Author(s): I. Pastan
- Abstract
Background
SS1P is a recombinant immunotoxin targeting the tumor differentiation antigen mesothelin, which is highly expressed in mesothelioma. Anti-tumor activity of SS1P was limited in phase I clinical trials due to development of neutralizing antibodies (NAbs) that limited treatment to one cycle. In immunocompetent mice P and C (P-C) can abrogate development of anti-SS1P NAbs. This pilot study was performed to determine the impact of P-C-based immune depletion on anti-SS1P NAb formation and to assess safety of P-C-SS1P.Methods
Patients with progressive pleural or peritoneal mesothelioma who previously received platinum-based therapy were eligible. Up to 6 cycles of P 4 mg/m2 IV (cycle 1: days 1, 5, 9; cycle 2-6: day 1); C 200 mg PO (cycle 1: days 1-12; cycle 2-6: days 1-4) and SS1P IV (35 µg/kg, cycle 1: days 10, 12, 14; cycle 2-6: days 2, 4, 6) were administered (cycle 1 was 30 days and cycles 2-6 were 21 days) with restaging every 2 cycles in the absence of progressive disease and anti-SS1P NAbs.Results
Eleven patients were enrolled. The median age was 52 years (range 43-68); male 7, female 4; pleural 9, peritoneal 2; median number of prior treatments was 3 (range 2-6). Three out of 10 evaluable patients had partial response with tumor regressions of 74%, 70% and 44% with complete resolution of metabolic activity in two patients and >70% reduction in the third (Table). The overall survival of these patients is 17+, 15+ and 18+ months. In addition, one patient with stable disease and one patient with progressive disease had dramatic response to post-SS1P chemotherapy using drugs to which they had not responded previously. All five patients who responded are alive with overall survival ranging from 11 to 18 months. The regimen of P-C delayed development of NAbs to SS1P, thereby allowing multiple cycles of therapy with SS1P. Only 2 of 10 (20%) patients developed anti-SS1P NAbs after one cycle compared to 88% of patients who received single agent SS1P in a previous study (p=0.0001), thus meeting the primary endpoint. The regimen of P-C-SS1P was safe and well tolerated and no patient developed opportunistic infections. Grade ≥ 3 adverse events were P-C related lymphopenia (100%), transaminitis (18%) and SS1P related back pain (9%), non-cardiac chest pain (18%) and fever (9%).Pt Overall Tumor Response[†] Delayed Tumor Response[§] Post Study Chemo. Response to Post-SS1P Chemo. Overall Survival (months) 1 PR (-44%) Yes (7 m+) - - 18.2+ 2 PR (-74%) - - - 17.1+ 3 SD - Yes PR (-55%)* 15+ 4 PR (-70%) - - - 14.5+ 5 SD - - - 8.8 6 PD - - - 6.2 7 PD - - - 5.7 8 PD Yes (4 m+)** Yes 85% decrease in tumor [18]F-FDG uptake[¶] 10.6+ 9 PD - - - 4.2 10 SD - Yes No 7.3 PR, partial response; SD, stable disease; PD, progressive disease; [18]F-FDG, Fluorodeoxyglucose; [†]In patients with tumor response the maximum percent decrease in tumor dimensions is shown; [§]Months from study initiation when response first observed; * PR to post-SS1P treatment with previously ineffective chemotherapy; **Patient 8 had initial PD, but at 4 months had 25% reduction in size of one of the target lesions and marked decrease of metabolic activity by PET; [¶]Patient 8 had 85% reduction in metabolic activity compared to baseline and SD by CT scan on post- SS1P chemotherapy. Conclusion
SS1P and immune depletion with P-C results in significant and durable anti-tumor activity in heavily pre-treated chemotherapy refractory patients with mesothelioma.
