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R. Hassan
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O22 - Mesothelioma III (ID 122)
- Event: WCLC 2013
- Type: Oral Abstract Session
- Track: Mesothelioma
- Presentations: 3
- 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)
16:15 - 17:45 | Author(s): R. Hassan
- 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. -
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O22.05 - Exposure-response Relationship of Amatuximab (AMA) in Combination with Pemetrexed and Cisplatin (P/C) in Patients with Unresectable Pleural Mesothelioma (ID 1609)
16:15 - 17:45 | Author(s): R. Hassan
- Abstract
- Presentation
Background
AMA is chimeric monoclonal antibody that binds to mesothelin, which is highly expressed in malignant mesothelioma and largely absent from normal tissue. In vitro studies indicate that AMA potentially has anti-tumor activity via antibody-dependent cellular cytotoxicity. AMA was studied in a Phase 2 mesothelioma trial.Methods
This was a global, single arm, open label Phase 2 trial in 89 patients with previously untreated epithelial or mixed histology unresectable malignant pleural mesothelioma. Subjects received P/C every three weeks for 4 to 6 cycles combined with AMA 5mg/kg on days 1 and 8 of each 21 day cycle. All patients were fully supplemented with folate and B12 as per pemetrexed label requirements. Single agent AMA was then continued in the same schedule until disease progression. The primary endpoint was progression-free survival (PFS) at 6 months with a secondary end point of overall survival (OS).Results
Median PFS was 6.1 months while median OS was 14.8 months. An evaluation of serum drug concentration relationship with clinical response noted that those subjects who achieved a median trough serum concentration of 32.9 µg/mL had an improved median PFS over those whose trough serum concentration was below the median (238 days vs 115 days, p<0.001). Similarly those subjects with a serum trough concentration of AMA above a median of 38.2 µg /mL had a median OS of 583 days while those with a median serum concentration of AMA below 38.2 µg /mL had a median OS of 375 days, p=0.0202. The most commonly reported adverse event was that of hypersensitivity to the chimeric antibody at first dose second cycle.Conclusion
The safety profile of AMA in combination with P/C was consistent with that seen previously for the PC regimen. Although PFS is not significantly different from historical results of P/C alone, the median OS was 14.8 months (as compared to 13.3 months for P/C[1]). PK/PD analysis demonstrated that AMA trough concentrations were a significant predictor of both PFS and OS where higher concentrations were associated with longer OS and PFS. [1]Reference: Vogelzang NJ, Rusthoven JJ, Symanowski J, et al. Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma. J Clin Oncol, 2003; 21:2636-2644.Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
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O22.08 - DISCUSSANT (ID 3973)
16:15 - 17:45 | Author(s): R. Hassan
- Abstract
- Presentation
Abstract not provided
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