| General information |
| Database: | DB00287 |
| Objective: | Thisphase Ib trial assessed the maximum tolerated dose (MTD) and safety of the Tolllike receptor 9 agonist IMO2055 combined with 5fluorouracil, cisplatin, and cetuximab (PFE) as firstline palliative treatment in patients with relapsed and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). |
| Authors: | Machiels JP, et al |
| Title: | Phase Ib trial of the Tolllike receptor 9 agonist IMO2055 in combination with 5fluorouracil, cisplatin, and cetuximab as firstline palliative treatment in patients with recurrent/metastatic squamous cell carcinoma of the head and neck. |
| Journal: | Invest New Drugs. |
| Year: | 2013 |
| PMID: | 23397499 |
| Trial Design |
| Clinical Trial Id: | EudraCT no. 201001845811 |
| Agent: | IMO2055
|
| Target: | Tolllike receptor 9
|
| Cancer Type: | head and neck cancer |
| Cancer Subtype: | advanced head and neck squamous cell carcinoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | IMO2055+ 5fluorouracil, cisplatin, + cetuximab as firstline palliative treatment |
| Study Type: | an openlabel, IIpart, phase Ib trial |
| Key Patients Feature: | Adult patients aged more than and equal to 18 years were eligible if they had a histologically or cytologically confirmed diagnosis of R/M SCCHN not suitable for local therapy, with more than and equal to 1 lesion measurable either by computed tomography scan or magnetic resonance imaging, and a Karnofsky performance status (KPS) of more than and equal to 70 or ECOG performance status of 0 or 1 at trial entry. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | A standard 3+3 study design was used. patients were sequentially enrolled to be treated with IMO2055 (0.16, 0.32, or 0.48 mg/kg/day; days 1, 8, 15), 5fluorouracil (1, 000 mg/m(2)/day; days 14), cisplatin (100 mg/m(2)/day; day 1) and cetuximab (400 mg/m(2)/day first dose; then 250 mg/m(2)/day; days 1, 8, 15) every 3 weeks. |
| Primary End Point: | The primary study objectives were to determine the MTD. |
| Secondary End Point: | the potential antitumor effect and clinical benefit, and cetuximab in terms of best response overall, disease control, duration of response, PFS and OS; pharmacodynamic parameters (biomarkers of IMO2055 effects), and immunogenicity against cetuximab; and the pharmacokinetic (PK) profile |
| Patients Number: | 13 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities (DLTs; ie, any Grade [G]3/4 treatmentrelated adverse events [TEAEs] in cycle 1) occurred in 2/4 patients treated with IMO2055 0.32 mg/kg (G4 hypokalemia and hypomagnesemia [n=1]; G4 septicemia, hyperthermia, febrile neutropenia, and G3 hypotension [n=1]). In the IMO2055 0.16mg/kg expansion cohort, 1 patient experienced DLTs of G3 sepsis, bacteremia, and hyperthermia. |
| Objective Response Rate: | Best response achieved overall was partial response in 3 patients and stable disease in 9 patients. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common G more than and equal to 3 TEAEs were neutropenia (n=9; not including febrile neutropenia [n=1]), hypokalemia (n=5), and hypomagnesemia (n=4). Serious adverse events (SAEs) occurred in 8 patients, including 4 with SAEs considered IMO2055 related; 1 of these patients died. |
| Conclusions: | Regimens combining IMO2055 and PFE cannot be recommended for further development in R/M SCCHN patients. |