Abstract 4404
Background
While early stage endometrial cancer (EC) is associated with a favorable prognosis, prognosis for advanced or recurrent EC is poor. Paclitaxel and carboplatin chemotherapy (CT) is often used as first-line treatment for these patients; however, there exists an imperative need for more effective and tolerable therapies. In KEYNOTE-146, combination therapy with the PD-1 inhibitor pembrolizumab (pembro) and the tyrosine kinase inhibitor lenvatinib resulted in an ORR of 39% in patients with EC (Makker et al. ASCO 2018). Based on these promising data, the ENGOT-EN9/LEAP-001 study was initiated to assess this combination therapy in women with recurrent or advanced EC.
Trial design
The ENGOT-EN9/LEAP-001 study (NCT03884101) is a phase 3, randomized, open-label, active-controlled trial comparing combination therapy with pembro and lenvatinib to paclitaxel and carboplatin CT in patients with newly diagnosed stage III-IV or recurrent EC (NCT03884101). Approximately 720 patients not previously treated with systemic chemotherapy (except as part of a chemoradiation regimen), antiangiogenic agents, PD-1 or PD-L1 inhibitors, or other T-cell receptor–targeted agents will be randomized 1:1 to pembro (200 mg Q3W) plus lenvatinib (20 mg daily) or paclitaxel and carboplatin CT (pac 175 mg/m2 plus carb AUC 6 Q3W). Patients will first be stratified by proficient vs deficient mismatch repair status (pMMR vs dMMR), and pMMR patients will be further stratified by ECOG performance status (0 vs 1), measurable disease (yes vs no), and prior chemoradiation (yes vs no). Treatment will continue until disease progression, initiation of new anticancer treatment, unacceptable adverse events, or withdrawal of consent for up to 35 cycles for pembro or 7 cycles of paclitaxel and carboplatin CT. Primary endpoints are PFS per RECIST v1.1, assessed by blinded independent central review, and OS. Secondary endpoints are ORR, health-related quality of life, safety and tolerability, and pharmacokinetics of lenvatinib. Exploratory endpoints include duration of response, disease control rate, and clinical benefit rate. Enrollment is ongoing.
Clinical trial identification
NCT03884101; 21, 2019.
Editorial acknowledgement
Nathan Rodeberg, PhD, and Diane Neer, ELS, of MedThink SciCom, funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc.
Legal entity responsible for the study
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA, are responsible for the governance, coordination and running of the study.
Funding
Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Eisai Inc., Woodcliff Lake, NJ, USA.
Disclosure
C. Vulsteke: Honoraria (self), Research grant / Funding (self): Roche; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (self): Leo-Pharma; Honoraria (self): Merck MSD; Honoraria (self): AstraZeneca; Honoraria (self): Astellas. V. Makker: Advisory / Consultancy: Eisai; Advisory / Consultancy: Merck; Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: ArQule; Research grant / Funding (self): Karyopharm; Research grant / Funding (self): AstraZeneca. I.A. McNeish: Honoraria (self): Clovis Oncology; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Takeda; Honoraria (self): Tesaro. L. Dutta: Full / Part-time employment: Eisai. C. Xu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. J. Lee: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck. S. Pignata: Honoraria (self), Research grant / Funding (institution): MSD; Honoraria (self), Research grant / Funding (institution): Roche; Research grant / Funding (institution): AstraZeneca; Honoraria (self): Clovis Oncology; Honoraria (self): Tesaro; Honoraria (self): Inctre. All other authors have declared no conflicts of interest.
Resources from the same session
3191 - The efficacy and safety of lenvatinib in patients who did not meet the inclusion criteria of the phase 3 trial (REFLECT trial) and those with BCLC Stage B hepatocellular carcinoma - A nationwide multicenter study in Japan-
Presenter: Azusa Sakamoto
Session: Poster Display session 2
Resources:
Abstract
1529 - Prognostic and predictive value of baseline alpha-fetoprotein (AFP) in patients with advanced hepatocellular carcinoma (HCC) treated with ramucirumab from two phase 3 studies (REACH, REACH-2)
Presenter: Andrew Zhu
Session: Poster Display session 2
Resources:
Abstract
2767 - Effect of second-line cabozantinib on health states for patients with advanced hepatocellular carcinoma (aHCC) after sorafenib: QTWiST analysis from the CELESTIAL study
Presenter: Nicholas Freemantle
Session: Poster Display session 2
Resources:
Abstract
2150 - Alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (HCC) in the phase 3 RESORCE trial
Presenter: Jordi Bruix
Session: Poster Display session 2
Resources:
Abstract
3437 - Phase I/II trial of NBTXR3 activated by SBRT in patients with hepatocellular carcinoma or liver metastasis
Presenter: Marc Pracht
Session: Poster Display session 2
Resources:
Abstract
1758 - Efficacy and safety of ramucirumab (RAM) for advanced hepatocellular carcinoma (HCC) with elevated alpha-fetoprotein (AFP) following first-line sorafenib across age subgroups in two global phase 3 trials (REACH and REACH-2)
Presenter: Masatoshi Kudo
Session: Poster Display session 2
Resources:
Abstract
1192 - Ramucirumab in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha fetoprotein (AFP): An exposure–response analysis
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1600 - Outcomes of Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab: The Mount Sinai Hospital Experience.
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2364 - Pembrolizumab vs Chemotherapy in Patients With Advanced/Metastatic Adenocarcinoma (AC) or Squamous Cell Carcinoma (SCC) of the Esophagus as Second-Line Therapy: Analysis of the Chinese Subgroup in KEYNOTE-181
Presenter: Jia Chen
Session: Poster Display session 2
Resources:
Abstract
1933 - A national comparative effectiveness study to assess definitive chemoradiation regimens in proximal oesophageal squamous cell cancer
Presenter: Judith de Vos-Geelen
Session: Poster Display session 2
Resources:
Abstract