Efthymiou, M;
Mackie, IJ;
Lane, P;
Erkan, D;
Cohen, H;
(2017)
High prevalence of activated protein C resistance associated with high avidity anti-protein C antibodies in various antiphospholipid syndrome clinical phenotypes.
In:
(Proceedings) ISTH 2017.
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Forster_CCR-18-1539_Patritumab ph1b SCCHN_manuscript_24Aug2018_FINAL.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Background: Patritumab plus cetuximab with platinum as first-line therapy for patients with recurrent and/or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) was evaluated for safety and to determine the recommended phase-II combination dose. Methods: Patients aged ≥18 years with confirmed R/M SCCHN received intravenous patritumab (18- mg/kg loading dose [LD]); 9-mg/kg maintenance dose [MD] every 3 weeks [q3w]) + cetuximab (400- mg/m2 LD; 250-mg/m2 MD weekly) + cisplatin (100 mg/m2 q3w) or carboplatin (area under the curve [AUC] of 5) for 6 cycles or until toxicity, disease progression, or withdrawal. Primary endpoints were dose-limiting toxicities (DLTs; grade ≥3 [21-day observation period]) and treatment-emergent adverse events (TEAEs). Pharmacokinetics, human antihuman antibodies (HAHA), tumor response, progression free survival (PFS), and overall survival (OS) were assessed. Results: Fifteen patients completed a median (range) of 8.7 (2.0-20.7) patritumab cycles. No DLTs were reported. Serious AEs were reported in 9 patients (patritumab-related n=4). TEAEs (N=15 patients) led to patritumab interruption in 7 patients. Patritumab-related dose reductions were reported in 1 patient. Patritumab (18 mg/kg) pharmacokinetics (N=15) showed mean (standard deviation) AUC0-21d of 2,619 (560) µg∙day/mL and maximum concentration of 499.9 (90.4) µg/mL. All patients were HAHA-negative at study end (single, transient low titer in 1 patient). Tumor response rate (complete plus partial response; N=15) was 47%. Median (95% confidence interval) PFS and OS (N=15) were 7.9 (3.7-9.7) and 13.5 (6.6- 17.5) months, respectively. Conclusion: Patritumab (18-mg/kg LD, 9-mg/kg MD) plus cetuximab/platinum was tolerable, active in SCCHN, and was selected as the phase II dose-regimen.
| Type: | Proceedings paper |
|---|---|
| Title: | High prevalence of activated protein C resistance associated with high avidity anti-protein C antibodies in various antiphospholipid syndrome clinical phenotypes |
| Event: | ISTH 2017 |
| Location: | Berlin, Germany |
| Dates: | 08-13 July 2017 |
| Open access status: | An open access version is available from UCL Discovery |
| Publisher version: | http://www.isth2017.org/ |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | patritumab, cetuximab, recurrent or metastatic squamous cell carcinoma of the head and neck, safety, dose-limiting toxicity |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10053269 |
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