dm+d

Unassigned

New Medicines

ZepzelcaSmall cell lung cancer (SCLC), after failure of one platinum-containing line

Information

Zepzelca
New molecular entity
PharmaMar
Jazz Pharmaceuticals

Development and Regulatory status

None
Phase III Clinical Trials
Launched
May 21Despite ATLANTIS failing to meet its primary endpoint, Jazz hopes to see continued growth in the 2L setting across both platinum-sensitive and -resistant patients. It also plans to initiate a PIII trial in combination with I/O in 1L ES-SCLC in 2021 [17].
Nov 20Zepzelca is available in the US [15].
Jun 20Approved in US [13].
Dec 19Filed in US [11].
Aug 19NDA to be submitted to FDA for accelerated approval in Q4 2019 [10].
Aug 18 FDA grants Orphan Drug Designation to lurbinectedin for treatment of sCLC [7].
Oct 17EU filing will be via the centralised procedure [5].
Aug 16PharmaMar announces the start of the ATLANTIS pivotal PIII trial (NCT02566993, EudraCT 2015-001641-89); the trial is expected to recruit patients from 21 countries [1].

Category

Alkylating agant; binds to DNA minor groove and inhibits RNA polymerase II
Lung cancer is the third most common cancers in the UK: about 45,500 new cases were diagnosed in the UK in 2013. About 10-15% of cases are classified as SCLC [2].
Small cell lung cancer (SCLC), after failure of one platinum-containing line
Intravenous infusion

Further information

Yes

Trial or other data

Sep 21Jazz is preparing to start another trial that will assess OS in relapsed SCLC, due to complete Q1 25. It will compare lurbinectedin 3.2 mg/m2 (day 1) 3-weekly with lurbinectedin 2.0 mg/m2 (day 1) + irinotecan 75mg/m2 (day 1 +8), every 3 weeks + GCSF, and with institutional choice of chemotherapy, and recruit in the US and Europe (incl. UK) [18].
Dec 20Pharmamar report that although ATLANTIS failed to improve OS, key secondary and subgroup analyses favoured the lurbinectedin combination arm. Lurbinectedin monotherapy was not tested in ATLANTIS. The FDA approved Zepzelca (lurbinectedin) under accelerated approval based on objective response rate (ORR) and duration of response (DoR) demonstrated in an open-label, monotherapy clinical study. Pharmamar and Jazz will provide the ATLANTIS data to FDA and look forward to working with the agency to determine the confirmatory data that is needed for full approval [16].
Dec 20PIII ATLANTIS study fails to meet primary outcome [14].
Jun 19PIII ATLANTIS study is on course to complete collection of primary outcome data in Feb 20 [12].
Jun 19Results of PII study presented at ASCO: Overall Response Rate of 35.2%; 45% in patients with sensitive disease (CTFI≥90 days, i.e., those who have suffered a relapse of the disease in a period greater than or equal to 90 days) and 22.2% in patients with resistant disease (CTFI<90 days, i.e., those patients who have suffered a relapse of the disease in a period less than 90 days). median survival was 9.3 months [9].
Sep 18PIII NCT02566993 study has finished recruiting; collection of primary outcome data expected to complete Feb 20 [8].
Dec 17The PIII NCT02566993 study is still recruiting. Estimated primary completion date remains as June 2019 [6].
Aug 16 the multi-centre, open-label, randomised PIII ATLANTIS study (NCT02566993, EudraCT 2015-001641-89) will compare lurbinectedin plus doxorubicin vs. topotecan or the combination VCR (cyclophosphamide, doxorubicin and vincristine) in patients with SCLC after failure of one platinum-containing line. Primary outcome is progression free survival (PFS); estimated recruitment 600, and estimated primary completion date June 2019 [3].

Evidence based evaluations