| General information |
| Database: | DB00688 |
| Objective: | 19TNF is an armed antibody that selectively targets human TNF to extra domain Bfibronectin on tumour blood vessels. They performed a phase I/II firstinman trial with L19TNF monotherapy in metastatic solid cancer patients to study safety and signs of clinical activity. |
| Authors: | Spitaleri G, et al |
| Title: | Phase I/II study of the tumourtargeting human monoclonal antibodycytokine fusion protein L19TNF in patients with advanced solid tumours. |
| Journal: | J Cancer Res Clin Oncol. |
| Year: | 2013 |
| PMID: | 23160853 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | L19TNF
|
| Target: | Tumour necrosis factor (TNF)
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced solid tumors |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | firstinmanphase I/II study |
| Key Patients Feature: | patients with histologically confirmed metastatic solid cancer, who had not receivedantitumour therapy for at least 4 weeks, were treated withL19TNF as a 60min intravenous infusion on day 1, 3, and 5of 3weekly cycles for up to 6 cycles. |
| Biomarker: | changes in lymphocyte subsets, 5HIAA plasma levels |
| Biomark Analysis: | no significant differences |
| Control Group Info: | single arm |
| Treatment Info: | Six cohorts of patients were treated with increasing (1.313 ¦Ìg/kg) doses of intravenous L19TNF on day 1, 3, and 5 of repeated 3weekly cycles, and 12 colorectal cancer patients were treated at 13 ¦Ìg/kg. |
| Primary End Point: | PK, MTD, DLTs, safety and clinical activity |
| Secondary End Point: | NA |
| Patients Number: | 34 |
| Trial Results |
| DLT_MTD: | Grade 3 lumbar pain in bone metastasis was the only doselimiting toxicity found in one patient.The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19TNF possibly in combination with chemotherapy. |
| Objective Response Rate: | Objective tumour responses were not detected. Transient stable disease occurred in 19 of 31 evaluable patients |
| Disease Control Rate: | 0.667 |
| Median Time to Progression: | Forphase I patients with SD, median timetoprogression (TTP) was 134 days (range 37-329). TTP forphase II patients waw 85 (range 77-120) |
| Median PFS A vs. C: | Forphase I patients with SD, median progression free survival (PFS) was 84 days (range 35-329). PFS forphase II patients was 77 (range 29-120). |
| Median OS A vs. C: | Median OS forphase I (n = 17) and II (n = 10) patients was 226 and 110 days, respectively, |
| Adverse Event(agent arm): | Mild chills, nausea and vomiting but no haemato or unexpected toxicity were observed. Grade 3 lumbar pain in bone metastasis was the only doselimiting toxicity found in one patient. |
| Conclusions: | Intravenous L19TNF on day 1, 3, and 5 of a 3weekly schedule was safe up to 13 ¦Ìgkg, but did not result in objective tumour responses. The maximally tolerated dose (MTD) was not reached, allowing for further dose escalation of L19TNF possibly in combination with chemotherapy. |