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|Ref Type||Journal Article|
|Authors||Meulendijks D, Jacob W, Voest EE, Mau-Sorensen M, Martinez-Garcia M, Taus A, Fleitas T, Cervantes A, Lolkema MP, Langenberg MHG, De Jonge MJ, Sleijfer S, Han JY, Calles A, Felip E, Kim SW, Schellens JHM, Wilson S, Thomas M, Ceppi M, Meneses-Lorente G, James I, Vega-Harring S, Dua R, Nguyen M, Steiner L, Adessi C, Michielin F, Bossenmaier B, Weisser M, Lassen UN|
|Title||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.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2017 Sep 15|
|Abstract Text||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. Clin Cancer Res; 23(18); 5406-15. ©2017 AACR.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||Cetuximab + Lumretuzumab||Phase Ib/II||Actionable||In a Phase Ib trial, treatment with the combination of Erbitux (cetuximab) and Lumretuzumab demonstrated minimal clinical efficacy in ERBB3 (HER3)-positive advanced solid tumor patients, resulting in an objective response rate of 6.1% (3/49), including two partial responses and a complete response in one patient with squamous cell carcinoma of the head and neck (PMID: 28600476).||28600476|
|Unknown unknown||Advanced Solid Tumor||not applicable||Erlotinib + Lumretuzumab||Phase Ib/II||Actionable||In a Phase Ib trial, treatment with the combination of Tarceva (erlotinib) and Lumretuzumab demonstrated minimal clinical efficacy in ERBB3 (HER3)-positive advanced solid tumor patients, resulting in an objective response rate of 4.2% (3/71), including a partial response in a patient with ovarian cancer and in two patients with squamous non-small cell lung carcinoma (PMID: 28600476).||28600476|