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Dose escalation and expansion phase I studies with the tumour-targeting antibody-tumour necrosis factor fusion protein L19TNF plus doxorubicin in patients with advanced tumours, including sarcomas
- Source :
- European journal of cancer (Oxford, England : 1990). 150
- Publication Year :
- 2021
-
Abstract
- Background L19TNF is a recombinant fusion protein composed of a human antibody fragment and human tumour necrosis factor. L19TNF targets the EDB domain of oncofetal fibronectin highly expressed in tumour vasculature and induces tumour remission in mouse tumours. We summarise two phase I trials testing a combination of L19TNF with doxorubicin in patients with solid tumours, particularly soft tissue sarcomas (STS). Patients and methods The first study, an open-label, dose-escalation and expansion phase I study of L19TNF plus doxorubicin, enrolled 27 patients. Three cohorts (10.4–17 μg/kg L19TNF) of patients received L19TNF intravenously at days 1, 3, and 5 and doxorubicin (75 mg/m2, then 60 mg/m2) on day 1 every 3 weeks. The expansion cohort enrolled patients with STS. The second study tried to re-escalate the doxorubicin dose to 75 mg/m2 with 13 μg/kg L19TNF. Among primary objectives was the establishment of a recommended dose (RD). Results The combination was safely applicable. Dose-limiting toxicity occurred either at 17 μg/kg L19TNF or at 75 mg/m2 doxorubicin. RD is 13 μg/kg L19TNF plus 60 mg/m2 doxorubicin. In 15 STS patients of the extension cohort evaluable for efficacy, antitumour activity was observed with complete remission in 1, partial remission in 1 and minor tumour shrinkage in 7 patients. The median overall survival for this heavily pretreated cohort was 14.9 months. Conclusion L19TNF can be safely applied in combination with doxorubicin and induces encouraging tumour remissions in patients with soft tissue sarcomas.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Necrosis
Time Factors
Soft Tissue Neoplasms
03 medical and health sciences
0302 clinical medicine
Antineoplastic Agents, Immunological
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Doxorubicin
Aged
Antibiotics, Antineoplastic
biology
business.industry
Soft tissue
Sarcoma
Middle Aged
medicine.disease
Fusion protein
030104 developmental biology
Treatment Outcome
030220 oncology & carcinogenesis
Toxicity
Cohort
biology.protein
Female
Antibody
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 18790852
- Volume :
- 150
- Database :
- OpenAIRE
- Journal :
- European journal of cancer (Oxford, England : 1990)
- Accession number :
- edsair.doi.dedup.....530bc72c55f6b6ce7cac26721a6ee751