Pneumologie 2015; 69 - V152
DOI: 10.1055/s-0035-1544763

Phase 2 HERALD study of patritumab (P) with erlotinib (E) in advanced NSCLC subjects (SBJs)

J von Pawel 1, J Tseng 2, M Dediu 3, C Schumann 4, B Moritz 5, J Mendell 6, X Jin 6, W Feng 6, C Copigneaux 6, RA Beckman 6
  • 1Asklepios Fachkliniken München Gauting
  • 2MD Anderson Cancer Center Orlando
  • 3Institute of Oncology Bucharest
  • 4Klinik für Pneumologie, Thoraxonkologie, Schlaf- und Beatmungsmedizin, Klinikverbund Kempten-Oberallgäu gGmbH
  • 5CESAR Central European Society for Anticancer Drug Research, EWIV, Vienna
  • 6Daiichi Sankyo Pharma Development, Edison

Background: P is a fully human anti-HER3 antibody that inhibits HER3 binding with its ligand heregulin (HRG). Preclinically, P enhances anti-tumor activity with EGFR inhibitors, prevents HER3 reactivation after anti-EGFR treatment, and inhibits HRG- dependent activation. Phase Ib showed that P, with E (150mg/day PO), was tolerated at 18mg/kg IV q3w.

Methods: This Ph2 randomized, placebo-controlled double-blind study assessed safety and efficacy of P+E vs. placebo (Pbo)+E in E-naïve sbjs with advanced NSCLC (2nd or later line).

215 sbjs were randomized to: 1) High Dose [HD]: P 18mg/kg IV q3w; 2) Low Dose [LD]: P: 18mg/kg IV X 1, 9mg/kg IV q3w maintenance; or 3) Pbo q3wk. All subjects received E 150mg/day PO. Endpoints included PFS (primary), and OS and safety (secondary). HRG, measured as mRNA, was prospectively hypothesized to be the primary predictive biomarker before database lock. High/Low HRG cutoff was set at the median of the blinded data.

Results: 212 sbjs comprised the ITT. Median (m) PFS for ITT for HD, LD, and Pbo arms was 1.4 mos (HR 0.98), 2.5 mos (HR 0.77), and 1.6 mos, respectively (p=NS). 101 sbjs (51 HRG high) had adequate tissue for HRG testing. PFS was significantly improved in the HRG high subgroup (Table). HRG low subgroup showed no improvement in PFS (HR 0.92) and OS (HR 1.05) vs. Pbo. Grade > 3 AE's (HD, LD, Pbo) included: diarrhea (11.4%, 8.5%, 4.2%) and rash (5.7%, 7.0%, 2.8%).

(Log-rank p-value: *< 0.03, †< 0.003)

High Dose

P + E

Low Dose

P + E

Pooled Doses

P + E

E Alone


mPFS (mos)






(95% CI)


(0.16, 0.85)*


(0.13, 0.66)†


(0.16, 0.67)†

mOS (mos)






(95% CI)


(0.50, 2.61)


(0.25, 1.41)


(0.39, 1.67)

Conclusions: P showed improved PFS in the HRG high, but not in the ITT population. P safety was similar to Pbo with the exception of manageable rash and gastrointestinal effects. HRG appears to be a predictive biomarker for P, confirming preclinical findings Schneider et al, Yonesaka et al, ASCO2014).

HERALD is the first randomized Pbo controlled trial in NSCLC to report a predictive biomarker for HER3. Based on these results, a 2-part (A, confirmation of HRG predictive value; B, pivotal HRG high only) Phase 3 study was initiated.