TY - JOUR
T1 - Phase Ib Study of Lumretuzumab Plus Cetuximab or Erlotinib in Solid Tumor Patients and Evaluation of HER3 and Heregulin as Potential Biomarkers of Clinical Activity
AU - Meulendijks, Didier
AU - Jacob, Wolfgang
AU - Voest, Emile E
AU - Mau-Sorensen, Morten
AU - Martinez-Garcia, Maria
AU - Taus, Alvaro
AU - Fleitas, Tania
AU - Cervantes, Andres
AU - Lolkema, Martijn P
AU - Langenberg, Marlies H G
AU - De Jonge, Maja J
AU - Sleijfer, Stefan
AU - Han, Ji-Youn
AU - Calles, Antonio
AU - Felip, Enriqueta
AU - Kim, Sang-We
AU - Schellens, Jan H M
AU - Wilson, Sabine
AU - Thomas, Marlene
AU - Ceppi, Maurizio
AU - Meneses-Lorente, Georgina
AU - James, Ian
AU - Vega-Harring, Suzana
AU - Dua, Rajiv
AU - Nguyen, Maitram
AU - Steiner, Lori
AU - Adessi, Celine
AU - Michielin, Francesca
AU - Bossenmaier, Birgit
AU - Weisser, Martin
AU - Lassen, Ulrik N
N1 - ©2017 American Association for Cancer Research.
PY - 2017/9/15
Y1 - 2017/9/15
N2 - Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas. Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib. Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR. Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels.
AB - Purpose: This study investigated the safety, clinical activity, and target-associated biomarkers of lumretuzumab, a humanized, glycoengineered, anti-HER3 monoclonal antibody (mAb), in combination with the EGFR-blocking agents erlotinib or cetuximab in patients with advanced HER3-positive carcinomas. Experimental Design: The study included two parts: dose escalation and dose extension phases with lumretuzumab in combination with either cetuximab or erlotinib, respectively. In both parts, patients received lumretuzumab doses from 400 to 2,000 mg plus cetuximab or erlotinib according to standard posology, respectively. The effect of HRG mRNA and HER3 mRNA and protein expression were investigated in a dedicated extension cohort of squamous non–small cell lung cancer (sqNSCLC) patients treated with lumretuzumab and erlotinib. Results: Altogether, 120 patients were treated. One dose-limiting toxicity (DLT) in the cetuximab part and two DLTs in the erlotinib part were reported. The most frequent adverse events were gastrointestinal and skin toxicities, which were manageable. The objective response rate (ORR) was 6.1% in the cetuximab part and 4.2% in the erlotinib part. In the sqNSCLC extension cohort of the erlotinib part, higher tumor HRG and HER3 mRNA levels were associated with a numerically higher disease control rate but not ORR. Conclusions: The toxicity profile of lumretuzumab in combination with cetuximab and erlotinib was manageable, but only modest clinical activity was observed across tumor types. In the sqNSCLC cohort, there was no evidence of meaningful clinical benefit despite enriching for tumors with higher HRG mRNA expression levels.
U2 - 10.1158/1078-0432.ccr-17-0812
DO - 10.1158/1078-0432.ccr-17-0812
M3 - Journal article
C2 - 28600476
SN - 1078-0432
VL - 23
SP - 5406
EP - 5415
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 18
ER -
