Introduction: The cancer incidence continues to rise worldwide. Medical innovation has a major impact on patient survival, but within drug development, it can take more than 10 years to obtain marketing authorisation (MA). The time required for access to therapeutic innovation remains critical, so France has developed a specific expanded access program named ATU, which allows the administration of drugs before the European Medicines Agency (EMA) approval. The purpose of this study is to put in perspective the average time to access antineoplastic drugs worldwide, taking into account ATU, US Food and Drug Administration (FDA) and EMA approvals. Methods: The ATU system allows the use of a medicine before its MA, under exceptional conditions. All antineoplastic drugs in oncology that have benefited from the ATU system are analysed in terms of tumour site, biomarkers and number of patients who have access to the drug. Results: Between 1st January 2007 and 31st December 2019, 36 of 64 drugs (56.2%) that received MA in oncology were assigned an ATU, to the benefit of 16,927 patients. Thanks

Decisions on market authorization (MA) and reimbursement have different durations across countries because of health technology assessment (HTA) procedures and negotiations between manufacturers and national authorities. To overcome this delay, France has implemented a Temporary Authorization for Use (ATU) program that allows early access to drugs before MA, in order to treat patients with unmet medical needs. The objectives of our study were to establish the added therapeutic benefit (ATB) of ATUs for solid tumors and to investigate the correlations between three tools evaluating ATB and survival outcomes and drug costs. Data on ATUs granted from January 2009 to December 2019 to treat solid tumors were analyzed. An assessment of their ATB was conducted using the American Society of Clinical Oncology‐Value Framework (ASCO‐VF), the European Society for Medical Oncology‐Magnitude Clinical Benefit Scale (ESMO‐MCBS) and the French HTA criterion, clinical added value (CAV). The latter score determines reimbursement and national market access. Thirty‐five drugs in 39 indications were granted ATUs. All of them obtained MA and derived a clinical benefit to be reimbursed by the Social Security. Twenty‐eight (71.8%) had CAV compared to preexisting therapies. 24/38 (63.2%) had a 4‐5 ESMO‐MCBS score and 19/33 (57.6%) had an ASCO‐VF score over 45. No correlations were found between cost, PFS, OS, CAV and ASCO‐VF score, while high ESMO‐MCBS scores were correlated to OS. In conclusion, many patients were treated with innovations before MA thanks to ATU, although there are discrepancies between ATB scales, hence the importance of international collaboration in the evaluation of innovative therapies.

BACKGROUND:The arrival of immunotherapies and targeted therapies challenged the authorities to make them available as soon as possible. France has effective tools, such as clinical trials (CTs) and a national early access program (temporary authorizations for use [ATUs] and temporary recommendations for use [RTUs]), allowing the use of innovative drugs, whether or not they have been authorized or used off-label, for cases that have reached a therapeutic impasse. METHODS: The methodology involved real-time data collec-

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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.