Valeria Lovato - Academia.edu (original) (raw)

Papers by Valeria Lovato

Ejc Supplements, Jul 1, 2008

Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain... more Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.Results: The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU. Toxicity was manageable and reversible, with no treatment-related deaths. Twenty-nine patients were evaluable for efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST). In a centralized radiology analysis, eight of 29 (28%) patients achieved a RECIST-confirmed objective response, including a complete response still ongoing 21 months after treatment beginning. The 12-month survival rate and median overall survival of the recommended dose–treated patients (n = 26) were 61.5% and 14.1 months, respectively.Conclusions: The repeated administration of L19-IL2 in combination with dacarbazine is safe and shows encouraging signs of clinical activity in patients with metastatic melanoma. This combination therapy is currently evaluated in a randomized phase II trial with patients with metastatic melanoma. Clin Cancer Res; 17(24); 7732–42. ©2011 AACR.

Neurological Sciences, Jul 18, 2022

Value in Health, Dec 1, 2020

Cell Adhesion & Migration, Jan 2, 2015

Braud (2015) The tumortargeting immunocytokine F16-IL2 in combination with doxorubicin: dose esca... more Braud (2015) The tumortargeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer,

Value in Health, Oct 1, 2018

Internal and Emergency Medicine, Sep 20, 2019

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown etiology and poor prognosis... more Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown etiology and poor prognosis. Little is known about the epidemiology of this disease; most of the studies are limited by small and restricted cohort studies. We aim to investigate the epidemiology of IPF in the Italian primary care setting using the Health Search Database (HSD) between January 2002 and June 2017. In an attempt to define cases of IPF we adopted iterative combinations of International Classification of Diseases Ninth Revision (ICD-9-CM) and other clinical investigations according to three different operational Algorithms. Incidence and prevalence rate, according to the three Algorithms defining IPF, were calculated and the association with candidate determinants [sex, age, gastro-esophageal reflux (GERD) and smoking status] was evaluated. We identified 1,104,307 eligible patients. The prevalence rate of IPF varies between 2.6 to 24.3 per 100.000 person-year, using algorithm 1 and from 0.8 to 7 using algorithm 3. The incidence rate of IPF varies between 1.25 and 3.77 per 100.000 person-years, using algorithm 1 and from 0.10 to 1.61 using algorithm 3. The mean adjusted incidence rate ratio of IPF, using algorithm 1, is 2.33 (95% CI 2.11–2.57) per 100.000 person-years. Over the study years, the trend of prevalence was statistically significantly increasing while the incidence rate started to increase in the last 3 years. The analyses on candidate determinants showed that patients aged 61 years or older, those suffering from GERD, and former smokers were statistically significantly at greater risk of incurring IPF. To our knowledge, this is one of the first European IPF epidemiological studies conducted in primary care. The increase of the incidence rates is likely due to a growing awareness for IPF among General Practitioners, while the increase of prevalence rates may be due to an increase of survival, a result of recent advances in the diagnosis, management and therapies for the disease.

Family Practice, Aug 11, 2022

Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of sever... more Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. Methods The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case–control study was performed. SMA cases have been classified according to a clinically based iterative process as “certain”, “probable” or “possible”. To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. Results The SMA prevalence combining “certain”, “probable” and “possible” cases was 5.1 per 100,000 in 2019 (i.e. 1.12 per 100,000 when limited to “certain” cases), while the yearly incidence rate ranged from 0.12 to 0.56 cases per 100,000. Comparing “certain” cases with matched controls, the presence of neurology visits (OR = 6.5; 95% CI: 1.6–25.6) and prescription of electromyography (OR = 4.6; 95% CI: 1.1–18.7) were associated with higher odds of SMA diagnosis. Conclusions Our findings suggest that primary care databases may be used to enhance the early identification of SMA. Additional efforts are needed to exploit the electronic health records of general practitioners to allow early recognition of SMA.

Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain... more Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.Results: The recommended dose of L19-IL2 in combination with dacarbazine wa...

PLOS ONE, May 5, 2022

It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generall... more It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generally, after the age of 5 years, presents a steep deterioration until puberty followed by a relative stability, as most abilities have been lost. Although it is possible to identify points of slope indicating early improvement, steep decline and relative stabilizations, there is still a lot of variability within each age group and it's not always possible to predict individual trajectories of progression from age only. The aim of the study was to develop a predictive model based on machine learning using an XGBoost algorithm for regression and report, explore and quantify, in a single centre longitudinal natural history study, the influence of clinical variables on the 6/12-months Hammersmith Motor Functional Scale Expanded score prediction (HFMSE). This study represents the first approach to artificial intelligence and trained models for the prediction of individualized trajectories of HFMSE disease progression using individual characteristics of the patient. The application of this method to larger cohorts may allow to identify different classes of progression, a crucial information at the time of the new commercially available therapies.

Family Practice

Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of sever... more Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. Methods The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case–control study was performed. SMA cases have been classified according to a clinically based iterative process as “certain”, “probable” or “possible”. To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. Results The SMA prevalence combining “certain”, “probable” and “possible” cases wa...

Journal of Clinical Oncology, 2011

2595 Background: F16-IL2 is a tumor-targeting immunocytokine composed of the antibody fragment F1... more 2595 Background: F16-IL2 is a tumor-targeting immunocytokine composed of the antibody fragment F16 (specific to the tumor marker A1 domain of tenascin) and of human interleukin-2 (IL2). Thorough preclinical work showed that F16-IL2 localizes selectively at tumor tissues and enhances the activity of certain anticancer drugs. In these phase Ib studies, we investigated F16-IL2 in combination with doxorubicin or paclitaxel, defining the recommended dose (RD) and assessing safety, tolerability, and early signs of activity. METHODS Cohorts of pretreated patients with progressive solid tumors received weekly administrations of 6 escalating doses of doxorubicin (up to 25mg/m2) or 8 escalating doses of paclitaxel (up to 90mg/m2), combined with F16-IL2 (up to 25 MioIU of IL2 equivalent) for a maximum of 6 months. Safety and efficacy were evaluated using CTC v3.0 and RECIST criteria. RESULTS 18 and 28 patients, with a median age of 63 years (37-75) and 64 years (42-79), were treated in the doxorubicin and paclitaxel combination trials, respectively. Toxicity was manageable with only few reversible G4 events, no serious unexpected adverse reactions, and no treatment related deaths. The RD was defined as 25 MioIU of F16-IL2 given in combination with 25mg/m2 doxorubicin or 90mg/m2 paclitaxel weekly. Objective responses and long-lasting disease stabilizations were observed, including 4 partial responses, 2 of which in heavily pretreated NSCLC patients and 1 still ongoing after 17 months from beginning of treatment. Among the evaluable patients treated with the paclitaxel or doxorubicin combination respectively, PFS rate at 3 months is 50% and 44% (n=24 and n=16) and 1-year survival rate is 41% and 38% (n=17 and n=13). CONCLUSIONS 25 Mio IU of F16-IL2 combined with full-dose doxorubicin or paclitaxel can be safely and repeatedly administered weekly to patients with solid tumors, and showed early signs of clinical activity. Based on preclinical evidence, these combination regimens are being administered to breast cancer patients in phase II trials. Moreover, starting from the observed promising signs of activity, a study of F16-IL2 in lung cancer patients is being planned.

Journal of Clinical Oncology, 2011

2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment spe... more 2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a marker of tumor angiogenesis, and of human interleukin-2 (IL2). L19-IL2 is able to selectively deliver IL2 to tumor tissues exploiting the expression of EDB on newly formed blood vessels. The recommended monotherapy dose (RD) of 22.5 MioIU IL2 equivalents (day 1, 3, and 5) of L19-IL2 was defined earlier. In this study, we investigated L19-IL2 in combination with dacarbazine in patients with metastatic melanoma, assessing safety, tolerability, and activity. METHODS The study consists of a dose confirmation part, during which 10 patients with metastatic melanoma were enrolled, followed by a fixed dose part, during which 22 chemo-naive metastatic melanoma patients were treated at the RD. Patients received intravenous infusions of L19-IL2 (10, 15 and 22.5 MioIU during dose confirmation, and 22.5 MioIU in the fixed dose part of the study) on day 1, 3 and 5 in combination with 1 g/m2 of dacarbazine on day 1, every 21 days. Up to 6 treatment cycles were given, followed by a maintenance phase during which only L19-IL2 was applied biweekly. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively. RESULTS Median age was 55 years (30-83). The RD was confirmed to be 22.5 MioIU. Toxicity was manageable and reversible, with no treatment related deaths. Twenty-nine out of 32 patients were evaluable for efficacy according to RECIST. In a centralized radiology analysis, 8/29 patients achieved RECIST-confirmed objective responses, including a complete response, still ongoing 21 months after start of treatment. The one-year survival rate was 61.5% and median overall survival was 14.4 months for all patients treated at RD. CONCLUSIONS L19-IL2 combined with dacarbazine, both at RD, can be safely and repeatedly administered to patients with metastatic melanoma, and showed promising signs of clinical activity. To further evaluate this combination therapy for metastatic melanoma, a controlled randomized phase II trial is ongoing.

Ejc Supplements, Jul 1, 2008

Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain... more Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.Results: The recommended dose of L19-IL2 in combination with dacarbazine was defined as 22.5 Mio IU. Toxicity was manageable and reversible, with no treatment-related deaths. Twenty-nine patients were evaluable for efficacy according to Response Evaluation Criteria in Solid Tumors (RECIST). In a centralized radiology analysis, eight of 29 (28%) patients achieved a RECIST-confirmed objective response, including a complete response still ongoing 21 months after treatment beginning. The 12-month survival rate and median overall survival of the recommended dose–treated patients (n = 26) were 61.5% and 14.1 months, respectively.Conclusions: The repeated administration of L19-IL2 in combination with dacarbazine is safe and shows encouraging signs of clinical activity in patients with metastatic melanoma. This combination therapy is currently evaluated in a randomized phase II trial with patients with metastatic melanoma. Clin Cancer Res; 17(24); 7732–42. ©2011 AACR.

Neurological Sciences, Jul 18, 2022

Value in Health, Dec 1, 2020

Cell Adhesion & Migration, Jan 2, 2015

Braud (2015) The tumortargeting immunocytokine F16-IL2 in combination with doxorubicin: dose esca... more Braud (2015) The tumortargeting immunocytokine F16-IL2 in combination with doxorubicin: dose escalation in patients with advanced solid tumors and expansion into patients with metastatic breast cancer,

Value in Health, Oct 1, 2018

Internal and Emergency Medicine, Sep 20, 2019

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown etiology and poor prognosis... more Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown etiology and poor prognosis. Little is known about the epidemiology of this disease; most of the studies are limited by small and restricted cohort studies. We aim to investigate the epidemiology of IPF in the Italian primary care setting using the Health Search Database (HSD) between January 2002 and June 2017. In an attempt to define cases of IPF we adopted iterative combinations of International Classification of Diseases Ninth Revision (ICD-9-CM) and other clinical investigations according to three different operational Algorithms. Incidence and prevalence rate, according to the three Algorithms defining IPF, were calculated and the association with candidate determinants [sex, age, gastro-esophageal reflux (GERD) and smoking status] was evaluated. We identified 1,104,307 eligible patients. The prevalence rate of IPF varies between 2.6 to 24.3 per 100.000 person-year, using algorithm 1 and from 0.8 to 7 using algorithm 3. The incidence rate of IPF varies between 1.25 and 3.77 per 100.000 person-years, using algorithm 1 and from 0.10 to 1.61 using algorithm 3. The mean adjusted incidence rate ratio of IPF, using algorithm 1, is 2.33 (95% CI 2.11–2.57) per 100.000 person-years. Over the study years, the trend of prevalence was statistically significantly increasing while the incidence rate started to increase in the last 3 years. The analyses on candidate determinants showed that patients aged 61 years or older, those suffering from GERD, and former smokers were statistically significantly at greater risk of incurring IPF. To our knowledge, this is one of the first European IPF epidemiological studies conducted in primary care. The increase of the incidence rates is likely due to a growing awareness for IPF among General Practitioners, while the increase of prevalence rates may be due to an increase of survival, a result of recent advances in the diagnosis, management and therapies for the disease.

Family Practice, Aug 11, 2022

Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of sever... more Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. Methods The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case–control study was performed. SMA cases have been classified according to a clinically based iterative process as “certain”, “probable” or “possible”. To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. Results The SMA prevalence combining “certain”, “probable” and “possible” cases was 5.1 per 100,000 in 2019 (i.e. 1.12 per 100,000 when limited to “certain” cases), while the yearly incidence rate ranged from 0.12 to 0.56 cases per 100,000. Comparing “certain” cases with matched controls, the presence of neurology visits (OR = 6.5; 95% CI: 1.6–25.6) and prescription of electromyography (OR = 4.6; 95% CI: 1.1–18.7) were associated with higher odds of SMA diagnosis. Conclusions Our findings suggest that primary care databases may be used to enhance the early identification of SMA. Additional efforts are needed to exploit the electronic health records of general practitioners to allow early recognition of SMA.

Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain... more Purpose: L19-IL2 is an immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a tumor angiogenesis marker, and of human interleukin-2 (IL2). L19-IL2 delivers IL2 to the tumor site exploiting the selective expression of EDB on newly formed blood vessels. Previously, the recommended dose of L19-IL2 monotherapy was defined as 22.5 million international units (Mio IU) IL2 equivalents. In this study, safety and clinical activity of L19-IL2 in combination with dacarbazine were assessed in patients with metastatic melanoma.Experimental Design: The first 10 studied patients received escalating doses of L19-IL2 on days 1, 3, and 5 in combination with 1 g/m2 of dacarbazine on day 1 of a 3-weekly therapy cycle. Subsequently, 22 patients received L19-IL2 at recommended dose plus dacarbazine. Up to six treatment cycles were given, followed by a maintenance regimen with biweekly L19-IL2.Results: The recommended dose of L19-IL2 in combination with dacarbazine wa...

PLOS ONE, May 5, 2022

It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generall... more It is known from previous literature that type II Spinal Muscular Atrophy (SMA) patients generally, after the age of 5 years, presents a steep deterioration until puberty followed by a relative stability, as most abilities have been lost. Although it is possible to identify points of slope indicating early improvement, steep decline and relative stabilizations, there is still a lot of variability within each age group and it's not always possible to predict individual trajectories of progression from age only. The aim of the study was to develop a predictive model based on machine learning using an XGBoost algorithm for regression and report, explore and quantify, in a single centre longitudinal natural history study, the influence of clinical variables on the 6/12-months Hammersmith Motor Functional Scale Expanded score prediction (HFMSE). This study represents the first approach to artificial intelligence and trained models for the prediction of individualized trajectories of HFMSE disease progression using individual characteristics of the patient. The application of this method to larger cohorts may allow to identify different classes of progression, a crucial information at the time of the new commercially available therapies.

Family Practice

Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of sever... more Background Spinal muscular atrophy (SMA) is a rare genetic disease with a broad spectrum of severity. Although an early diagnosis of SMA is crucial to allow proper management of patients, the diagnostic delay is still an issue. Therefore, this study aimed to investigate the clinical correlates of SMA among primary care patients. Methods The Health Search Database (HSD) was adopted. To estimate the prevalence and incidence rate of SMA, a cohort study was conducted on the population (aged ≥6 years) being registered in HSD from 1 January 2000 up to 31 December 2019. To investigate the clinical correlates of SMA, a nested case–control study was performed. SMA cases have been classified according to a clinically based iterative process as “certain”, “probable” or “possible”. To test the association between clinical correlates and SMA cases a multivariate conditional logistic regression model was estimated. Results The SMA prevalence combining “certain”, “probable” and “possible” cases wa...

Journal of Clinical Oncology, 2011

2595 Background: F16-IL2 is a tumor-targeting immunocytokine composed of the antibody fragment F1... more 2595 Background: F16-IL2 is a tumor-targeting immunocytokine composed of the antibody fragment F16 (specific to the tumor marker A1 domain of tenascin) and of human interleukin-2 (IL2). Thorough preclinical work showed that F16-IL2 localizes selectively at tumor tissues and enhances the activity of certain anticancer drugs. In these phase Ib studies, we investigated F16-IL2 in combination with doxorubicin or paclitaxel, defining the recommended dose (RD) and assessing safety, tolerability, and early signs of activity. METHODS Cohorts of pretreated patients with progressive solid tumors received weekly administrations of 6 escalating doses of doxorubicin (up to 25mg/m2) or 8 escalating doses of paclitaxel (up to 90mg/m2), combined with F16-IL2 (up to 25 MioIU of IL2 equivalent) for a maximum of 6 months. Safety and efficacy were evaluated using CTC v3.0 and RECIST criteria. RESULTS 18 and 28 patients, with a median age of 63 years (37-75) and 64 years (42-79), were treated in the doxorubicin and paclitaxel combination trials, respectively. Toxicity was manageable with only few reversible G4 events, no serious unexpected adverse reactions, and no treatment related deaths. The RD was defined as 25 MioIU of F16-IL2 given in combination with 25mg/m2 doxorubicin or 90mg/m2 paclitaxel weekly. Objective responses and long-lasting disease stabilizations were observed, including 4 partial responses, 2 of which in heavily pretreated NSCLC patients and 1 still ongoing after 17 months from beginning of treatment. Among the evaluable patients treated with the paclitaxel or doxorubicin combination respectively, PFS rate at 3 months is 50% and 44% (n=24 and n=16) and 1-year survival rate is 41% and 38% (n=17 and n=13). CONCLUSIONS 25 Mio IU of F16-IL2 combined with full-dose doxorubicin or paclitaxel can be safely and repeatedly administered weekly to patients with solid tumors, and showed early signs of clinical activity. Based on preclinical evidence, these combination regimens are being administered to breast cancer patients in phase II trials. Moreover, starting from the observed promising signs of activity, a study of F16-IL2 in lung cancer patients is being planned.

Journal of Clinical Oncology, 2011

2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment spe... more 2531 Background: L19-IL2 is a tumor-targeting immunocytokine composed of an antibody fragment specific to the EDB domain of fibronectin, a marker of tumor angiogenesis, and of human interleukin-2 (IL2). L19-IL2 is able to selectively deliver IL2 to tumor tissues exploiting the expression of EDB on newly formed blood vessels. The recommended monotherapy dose (RD) of 22.5 MioIU IL2 equivalents (day 1, 3, and 5) of L19-IL2 was defined earlier. In this study, we investigated L19-IL2 in combination with dacarbazine in patients with metastatic melanoma, assessing safety, tolerability, and activity. METHODS The study consists of a dose confirmation part, during which 10 patients with metastatic melanoma were enrolled, followed by a fixed dose part, during which 22 chemo-naive metastatic melanoma patients were treated at the RD. Patients received intravenous infusions of L19-IL2 (10, 15 and 22.5 MioIU during dose confirmation, and 22.5 MioIU in the fixed dose part of the study) on day 1, 3 and 5 in combination with 1 g/m2 of dacarbazine on day 1, every 21 days. Up to 6 treatment cycles were given, followed by a maintenance phase during which only L19-IL2 was applied biweekly. Tumor assessment was performed every 6 weeks. Data on safety and efficacy were evaluated using CTC v3.0 and RECIST criteria, respectively. RESULTS Median age was 55 years (30-83). The RD was confirmed to be 22.5 MioIU. Toxicity was manageable and reversible, with no treatment related deaths. Twenty-nine out of 32 patients were evaluable for efficacy according to RECIST. In a centralized radiology analysis, 8/29 patients achieved RECIST-confirmed objective responses, including a complete response, still ongoing 21 months after start of treatment. The one-year survival rate was 61.5% and median overall survival was 14.4 months for all patients treated at RD. CONCLUSIONS L19-IL2 combined with dacarbazine, both at RD, can be safely and repeatedly administered to patients with metastatic melanoma, and showed promising signs of clinical activity. To further evaluate this combination therapy for metastatic melanoma, a controlled randomized phase II trial is ongoing.