RT Journal Article
T1 Randomized Phase II Trial of Seribantumab in Combination with Erlotinib in Patients with EGFR Wild-Type Non-Small Cell Lung Cancer.
A1 Sequist, Lecia V
A1 Gray, Jhanelle Elaine
A1 Harb, Wael A
A1 Lopez-Chavez, Ariel
A1 Doebele, Robert C
A1 Modiano, Manuel R
A1 Jackman, David Michael
A1 Baggstrom, Maria Quintos
A1 Atmaca, Akin
A1 Felip, Enriqueta
A1 Provencio, Mariano
A1 Cobo, Manuel
A1 Adiwijaya, Bambang
A1 Kuesters, Geoffrey
A1 Kamoun, Walid S
A1 Andreas, Karen
A1 Pipas, J Marc
A1 Santillana, Sergio
A1 Cho, Byoung Chul
A1 Park, Keunchil
A1 Shepherd, Frances A
K1 Antibody
K1 Biomarkers
K1 HER3/ErbB3
K1 Heregulin
K1 Seribantumab
K1 Targeted therapy
K1 Translational
AB Seribantumab (MM-121) is a fully human IgG2 monoclonal antibody that binds to human epidermal growth factor receptor 3 (HER3/ErbB3) to block heregulin (HRG/NRG)-mediated ErbB3 signaling and induce receptor downregulation. This open-label, randomized phase 1/2 study evaluated safety and efficacy of seribantumab plus erlotinib in advanced non-small cell lung cancer (NSCLC). Here, we report the activity of seribantumab plus erlotinib, versus erlotinib alone, in patients with EGFR wild-type tumors and describe the potential predictive power of HRG. Patients with EGFR wild-type NSCLC were assigned randomly to receive seribantumab + erlotinib or erlotinib alone. Patients underwent pretreatment core needle biopsy and archived tumor samples were collected to support prespecified biomarker analyses. One hundred twenty-nine patients received seribantumab + erlotinib (n = 85) or erlotinib alone (n = 44). Median estimated progression-free survival (PFS) in the unselected intent-to-treat (ITT) population was 8.1 and 7.7 weeks in the experimental and control arm, respectively (hazard ratio [HR], 0.822; 95% confidence interval [CI], 0.37-1.828; p = 0.63), and median estimated overall survival was 27.3 and 40.3 weeks in the experimental and control arm, respectively (HR, 1.395; 95% CI, 0.846 to 2.301; p = .1898) In patients whose tumors had detectable HRG mRNA expression, treatment benefit was observed in the seribantumab + erlotinib combination (HR, 0.35; 95% CI, 0.16-0.76; p = .008). In contrast, in patients whose tumors were HRG negative, the HR was 2.15 (95% CI, 0.97-4.76; p = .059, HRG-by-treatment interaction, p value = .0016). The addition of seribantumab to erlotinib did not result in improved PFS in unselected patients. However, predefined retrospective exploratory analyses suggest that detectable HRG mRNA levels identified patients who might benefit from seribantumab. An ongoing clinical trial of seribantumab, in combination with docetaxel, is underway in patients with advanced NSCLC and high HRG mRNA expression (NCT02387216). The poor prognosis of patients with non-small cell lung cancer (NSCLC) underscores the need for more effective treatment options, highlighting the unmet medical need in this patient population. The results of this study show that a novel biomarker, heregulin, may help to identify patients with advanced NSCLC who could benefit from treatment with seribantumab. On the basis of the observed safety profile and promising clinical efficacy, a prospective, randomized, open-label, international, multicenter phase II trial (SHERLOC, NCT02387216) is under way to investigate the efficacy and safety of seribantumab in combination with docetaxel in patients with heregulin-positive advanced adenocarcinoma.
YR 2019
FD 2019-04-11
LK http://hdl.handle.net/10668/13817
UL http://hdl.handle.net/10668/13817
LA en
DS RISalud
RD Apr 17, 2025