Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22030-e22030
Author(s):  
Claire Christen ◽  
Laetitia Belgodere ◽  
Bernard Guillot ◽  
Ghania Kerouani-Lafaye ◽  
Liora Brunel ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Malignant Melanoma ◽  
Early Stage ◽  
Objective Response ◽  
Time Data ◽  
National Agency ◽  
Innovative Drug ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

e22030 Access to innovation through the French Expanded-Access Program and clinical trials in patients with malignant melanoma Background: The arrival of immunotherapy (IT) and targeted therapy (TT) has constituted a revolution in the treatment of metastatic melanoma (MM) since the 2010s. The major challenge was to allow these new treatments to make them available as soon as possible. France has effective tools such as clinical trials (CT) and an expanded-access program (EPA) (through temporary use authorizations (ATU) and temporary use recommendations (RTU)) allowing the use of innovative drug without marketing authorization (MA) in case of therapeutic “dead-end”. Methods: Real-time data collection of nominal and cohort ATU, RTU (between 01/09/2009 and 01/09/2019), and CT authorizations (from 01/12/2017 to 01/09/2019) filed and evaluated by the French national agency for medicines and health products safety (ANSM) in the MM from internal databases. Clinical data of the cATU come from the summary reports produced by the laboratory. Results: 45 CT were authorized in MM, including 51% in early phases and 44% in phase II/III, mainly in the metastatic stage (86%) and with an industrial promoter (73%). IT and TT (63% and 24% respectively) are the most used in experimental arms, mostly in combination. Through the EPA, 3 RTUs were authorized in the adjuvant treatment of MM, 14 drugs benefited of a nATU and 5 obtained a cATU. This has treated 6538 patients (28% of nATU and 72% of cATU). The anti-PD1 and combination therapy of BRAF and MEK inhibitors are the most used, mainly in combination. 80% of the indications are from the second line. The duration of availability of the ATU is 9,85 months before obtaining the MA. Efficacy data in patients receiving cATU of vemurafenib and combination of cobimetinib and vemurafenib showed respectively the following objective response rate (ORR): at 8 weeks of treatment, ORR = 57,7% and 54,7%; at 20 weeks, ORR = 36,7% and 54,7% (IR criteria). For pembrolizumab, at 12 weeks, ORR = 29,7% and at 24 weeks, ORR = 40% (irRC criteria). All of these drugs obtained a MA and an inscription on the reimbursement list after the health technology assessment. Conclusions: Thanks to CT and the French EPA, patients were able to benefit from innovative treatments at an early stage of MM.

scholarly journals Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Giovanni Grignani ◽  
Vanna Chiarion Sileni ◽  
Carmine Pinto ◽  
Roberta Depenni ◽  
Nicola Fazio ◽  
...  
Keyword(s):  
Partial Response ◽  
Cell Carcinoma ◽  
Merkel Cell Carcinoma ◽  
Objective Response ◽  
Complete Response ◽  
Trial Participation ◽  
Merkel Cell ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

Abstract Background The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP. Methods Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician’s discretion. Results Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5–41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]). Conclusions Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.

scholarly journals Erdafitinib treatment in Brazilian patients with metastatic urothelial carcinoma (mUC): real-world evidence from an Expanded Access Program

2021 ◽  
Vol 13 ◽  
pp. 175883592110154
Author(s):  
Fernando Sabino M. Monteiro ◽  
Adriano Gonçalves e Silva ◽  
Andrea Juliana P. de S. Gomes ◽  
Carolina Dutra ◽  
Naira Oliveira Ferreira ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Real World ◽  
Objective Response ◽  
Significant Activity ◽  
Efficacy And Safety ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Real World Evidence ◽  
Metastatic Urothelial Carcinoma ◽  
Access Program

Background: Erdafitinib is the first targeted therapy approved for the treatment of patients with metastatic urothelial carcinoma (mUC). Approval was based on a phase II single-arm trial that demonstrated significant activity of erdafitinib in patients with tumors harboring FGFR2/3 alterations. In Brazil, an Expanded Access Program (EAP) provided patients with early access to erdafitinib prior to market authorization. The current report describes characteristics and outcomes of patients with mUC on erdafitinib therapy. Methods: Patients with mUC that failed first- and second-line systemic therapies were screened for FGFR2/3 alterations in primary or metastatic tumor tissues. Patients with FGFR2/3 alterations were selected to receive erdafitinib at the standard dosing schedule and were followed prospectively to evaluate the efficacy and safety outcomes. Results: From 19 April 2019, through 13 March 2020, 47 patients with mUC from 10 Brazilian centers were tested for FGFR2/3 alterations. Alterations in FGFR2/3 were found in 12 patients (25.5%) and all of them were eligible for the EAP. Four patients (33%) had partial response, while two patients (17%) had stable disease. Progressive disease, the best response, was observed in five patients (42%). At a median follow-up of 16.2 months, the median time to treatment failure (TTF) was 2.8 months. When considering only patients with objective response, the median TTF was 5.3 months. Adverse events (AEs) were reported for any grade and grade 3 or higher in 10 patients (83%) and 5 patients (42%), respectively. The most common AE was hyperphosphatemia. Conclusion: This first real-world evidence report of heavily treated patients with mUC confirms the efficacy and safety of erdafitinib in a disease setting with a lack of treatment options.

scholarly journals Experience of the nivolumab use in patients with metastatic renal cell carcinoma provided under the expanded access program in Russia. Subgroup analysis of the correlation between expression markers and the effectiveness of nivolumab therapy

2022 ◽  
Vol 11 (3) ◽  
pp. 23-35
Author(s):  
N.  V. Karpova ◽  
M.  V. Ivanov ◽  
V.  A. Mileiko ◽  
A.  A. Rumyantsev ◽  
T.  A. Titova ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Objective Response ◽  
Predictive Biomarkers ◽  
Principal Component ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

Abstract: Nivolumab was registered in Russia in December 2016 as a monotherapy for advanced renal cell carcinoma (RCC) and it remains a second‑line treatment choice for patients with disease progression after the use of tyrosine kinase inhibitors. Even though immunotherapy has already proven to be an effective approach for the treatment of RCC, predictive biomarkers for the rational selection of patients remain unidentified.Seventy‑five patients with metastatic renal cell carcinoma (mRCC) who received nivolumab in the 2nd and subsequent lines of therapy from 2015 to 2020 under the expanded access program were enrolled in this study. The objective response rate was 21,3 %. Median progression‑free survival (PFS) was 5,5 months. Median overall survival (OS) was not reached.To analyze molecular biomarkers correlated with the response to immunotherapeutic treatment, we performed whole‑transcriptome RNA sequencing of 16 samples (FFPE) in 15 patients with the assessment of the expression level for individual genes (PDCD1, CD274, CD8A, CD8B, CD4) and gene signatures (Angio, Teff, Myeloid Inflammation).Disease control rates were not different for the subgroups of patients with high and low expression of any of the signatures examined, and further principal component analysis did not reveal clustering of patients with and without objective response.Further studies on a larger sample of patients will help confirm or deny the predictive role of biomarkers selected for analysis in a heterogeneous population of RCC patients.

Durable remissions with Ipilimumab in pretreated metastatic malignant melanoma (MMM) patients (pts): Results of a South African Expanded Access Program (EAP).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20112-e20112
Author(s):  
Daniel A. Vorobiof ◽  
Bernardo Leon Rapoport ◽  
Lydia Mary Dreosti ◽  
Adam L. Nosworthy ◽  
Georgina Laird McAdam ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
South African ◽  
Metastatic Malignant Melanoma ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Access Program

scholarly journals Ipilimumab in Pretreated Patients With Advanced Malignant Melanoma: Results of the South African Expanded-Access Program

2017 ◽  
Vol 3 (5) ◽  
pp. 515-523 ◽  
Author(s):  
Bernardo L. Rapoport ◽  
Daniel A. Vorobiof ◽  
Lydia M. Dreosti ◽  
Adam Nosworthy ◽  
Georgina McAdam ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
South African ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Expanded Access ◽  
Expanded Access Program ◽  
Advanced Malignant Melanoma ◽  
Pretreated Patients ◽  
Access Program

Purpose The primary objective of this study was to evaluate 1- and 2-year survival rates and durable remissions in pretreated patients with advanced (unresectable or metastatic) malignant melanoma treated with ipilimumab in a South African expanded-access program (SA-EAP). Patients and Methods This multicenter, retrospective study obtained data from pretreated patients with advanced malignant melanoma who were eligible for the ipilimumab SA-EAP. Ipilimumab was administered at a dose of 3 mg/kg intravenously every 3 weeks for four cycles to adults with advanced melanoma for whom at least one line of treatment for metastatic disease had failed. Data from the medical records of 108 patients treated within the SA-EAP were collected and statistically analyzed to determine overall (OS) and progression-free survival (PFS) at 1 and 2 years. Results In the population of 108 patients, a median OS of 8.98 months (95% CI, 7.47 to 10.79 months) was observed. One-year OS was 36% (95% CI, 26% to 45%), and 2-year survival was observed as 20% (95% CI, 12% to 27%). The median survival without progression (ie, PFS) was 3.44 months (95% CI, 2.98 to 4.16 months), and 1- and 2-year PFS were 22% (95% CI, 14% to 29%) and 14% (95% CI, 8% to 21%), respectively. The longest recorded survival was 3.4 years. No independent prognostic variables were identified to predict for OS by multivariate Cox proportional hazards model. Conclusion In this multicenter South African setting, ipilimumab at a dose of 3 mg/kg was an effective treatment with long-term OS in a subset of patients with pretreated advanced malignant melanoma.

IPILIMUMAB IN PATIENTS WITH DISSEMINATED MELANOMA: THE N.N. PETROV NATIONAL MEDICAL RESEARCH CENTER OF ONCOLOGY EXPANDED ACCESS PROGRAM EXPERIENCE

2018 ◽  
Vol 64 (3) ◽  
pp. 388-393
Author(s):  
Yekaterina Anokhina ◽  
V. Rubinchik ◽  
Yekaterina Yaremenko ◽  
Gulfiya Teletaeva ◽  
Dilorom Latipova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Medical Research ◽  
Research Center ◽  
Expanded Access ◽  
Risk Of Death ◽  
National Medical ◽  
Expanded Access Program ◽  
Access Program

Ipilimumab (IPI) provides a ten-year overall survival in almost 20 % of selected patients participated in several phase II-III trials. However, the expanded access program (EAP) looks more like routine practice than like clinical trials& This is why the results of such application could be different. Here we present the long-term follow-up data of single center EAP. Ninety-six patients with disseminated melanoma progressing after at least one lines of drug therapy were included at the N.N. Petrov National Medical Research Center of Oncology. Sixty-seven (70 %) patients had stage IV M1c, 35 patients (36 %) had elevated LDH before initiating IPI therapy. All patients received IPI 3 mg / kg IV every 3 weeks for a maximum of 4 cycles. Totally, 320 cycles (mean - 3.3 per patient) were conducted. Grade 3-4 immuno-mediated adverse events (imAE) observed in 18 (19 %) patients. Three patients died of adverse events, possibly associated with ongoing therapy. The median time to progression was 3 (95 % CI, 2.4 to 3.5) mo., the median overall survival was 13 (95 % CI, 8.3 to17.6) mo. Previous immunotherapy with dendritic cell vaccines decreased the risk of death by 48 % (Log-rank p = 0.049). The wild type BRAF status increased three-year overall survival from 29 to 68 % (p = 0.042). Our data confirms long-term safety and efficacy of IPI in patients with pretreated disseminated melanoma in the close to real practice setting.

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