2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #359)
J Clin Oncol 37, 2019 (suppl; abstr 9036)
Author(s): Lecia V. Sequist, Pasi A. Janne, Rudolf M. Huber, Jhanelle Elaine Gray, Enriqueta Felip, Maurice Perol, Fred R. Hirsch, Daniel Shao-Weng Tan, Geoffrey Kuesters, Alena Zalutskaya, Sergio Santillana, J. Marc Pipas, Frances A. Shepherd; Massachusetts General Hospital Cancer Center/Harvard Medical School, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Medizinische Klinik Innenstadt, Munich, Germany; H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL; Vall d´Hebron University Hospital, Barcelona, Spain; Department of Thoracic Oncology, Centre Léon Bérard, Lyon, France; University of Colorado Cancer Center, Denver, CO; National Cancer Center, Singapore, Singapore; Merrimack Pharmaceuticals, Cambridge, MA; Merrimack Pharmaceuticals., Inc., Cambridge, MA; Merrimack Pharmaceuticals. Inc., Cambridge, MA; Cancer Clinical Research Unit, Princess Margaret Cancer Centre, Toronto, ON, Canada
Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w (experimental; exp) or docetaxel 75 mg IV q3w alone (control). Primary endpoint was PFS. Key secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse event (AEs) profile. Results: At a pre-specified interim analysis of 75% of total PFS events, 108 pts were enrolled (exp n = 71, control n = 37). Median age was 62y (range 34-83y); female 34%; one prior treatment only 39%. Median PFS was 3.0m for exp and 4.0m for control, HR = 1.66m (p = 0.084). Median OS was 7.9m for exp and 8.4m for control, HR = 1.50 (p = 0.235). ORR was 19.7% for exp and 5.6% for control (p = 0.052). Serious AEs were more frequent in the exp arm (40.8%) vs control (24.3%). Most common treatment emergent AEs (TEAEs) in the exp arm were diarrhea (47%), fatigue (37%), and neutropenia (27%). Based on a determination of futility at interim analysis, the study was terminated early. Conclusions: Seribantumab failed to improve PFS when added to docetaxel among previously treated advanced HRG+ NSCLC pts. A higher response rate and a higher incidence of TEAEs were observed in the exp arm. No further study of seribantumab is planned in NSCLC. Clinical trial information: NCT02387216