| General information |
| Database: | DB00685 |
| Objective: | To determine the maximum tolerated dose (MTD) of these agents combined during thisphase I study, patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg(1)) every 12 weeks plus subcutaneous PF3512676 (0.05, 0.10, or 0.15 mg kg(1)) weekly. |
| Authors: | Millward M, et al |
| Title: | Phase I study of tremelimumab (CP675 206) plus PF3512676 (CPG 7909) in patients with melanoma or advanced solid tumours. |
| Journal: | Br J Cancer. |
| Year: | 2013 |
| PMID: | 23652314 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | tremelimumab
|
| Target: | cytotoxic Tlymphocyteassociated antigen 4 (CTLA4)
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | com |
| Therapeutic Combination Type: | 1 |
| Therapeutic Combination Content: | tremelimumab (CP675 206) plus PF3512676 (CPG 7909) |
| Study Type: | a phase I, openlabel, nonrandomised, doseescalation study |
| Key Patients Feature: | Adult patients (X18 years) with histologically documented unresectable stage III or stage IV melanoma, oradult patients with advanced solid tumours and no standardtreatment options, were eligible for study participation. Measurableor evaluable disease was not required; therefore, it was expectedthat not all patients would be evaluable for efficacy. Patients withresected stage IV melanoma were also eligible. patients wererequired to have an Eastern Cooperative Oncology Group (ECOG)performance status of 0 or 1, and adequate bone marrow (absoluteneutrophil count X1.5 109 cells per l, platelets X100 109 per l, and haemoglobin X10gdl 1), hepatic (aspartate and alanineaminotransferase levels p2.5 upper limit of normal (ULN), totalbilirubin p2 ULN, and serum creatinine p2.0mgdl 1 orcalculated creatinine clearance X60mlmin 1), and renal function. patients were also required to have a serum lactatedehydrogenase level p2 ULN, consistent with ongoing trials oftremelimumab in melanoma. Patients with brain metastases, uncontrolled cardiac disease, active or chronic viral hepatitis, a history of other malignancies (except for adequately treated basalcell skin cancer, squamous cell skin cancer, or cervical cancer), orchronic autoimmune or antibodymediated diseases, and apotential requirement for systemic corticosteroids or concurrentimmunosuppressive therapy were excluded. Eligible patients werenot allowed to have received prior treatment with any antiCTLA4monoclonal antibody or TLR9 agonist or to have received anyanticancer agents, including immunotherapy, within 4 weeksbefore study entry. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | patients received intravenous tremelimumab (6.0, 10.0, or 15.0 mg kg(1)) every 12 weeks plus subcutaneous PF3512676 (0.05, 0.10, or 0.15 mg kg(1)) weekly. |
| Primary End Point: | safety and tolerability |
| Secondary End Point: | pharmacokinetics and antitumour activity |
| Patients Number: | 21 |
| Trial Results |
| DLT_MTD: | Doselimiting toxicities (prespecified 6week observation) occurred in one of the six patients in the 10 mg kg(1) tremelimumab plus 0.05 mg kg(1) PF3512676 cohort (grade 3 hypothalamopituitary disorder) and two of the six patients in the 15 mg kg(1) tremelimumab plus 0.05 mg kg(1) PF3512676 cohort (grade 3 diarrhoea). Consequently, 15 mg kg(1) tremelimumab plus 0.05 mg kg(1) PF3512676 exceeded the MTD. |
| Objective Response Rate: | Two melanoma patients achieved durable (more than and equal to 170 days) partial response. No human antihuman antibody responses to tremelimumab were observed. |
| 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): | Injectionsite reactions (n 21; 100%), influenzalike illness (n 18; 86%), and diarrhoea (n 13; 62%) were the most common treatmentrelated adverse events (TAEs). Grade X3 TAEs were reported (n 7; 33%). |
| Conclusions: | weekly PF3512676 (less than and equal to 0.15 mg kg(1)) plus tremelimumab (less than and equal to 10 mg kg(1) every 12 weeks) was tolerable. |