HER2 inhibition in gastro-oesophageal cancer: A review drawing on lessons learned from breast cancer

Table 3 Selected clinical trials currently underway targeting HER2 in advanced and metastatic HER2-amplified gastro-oesophageal cancer

Official study title	Stage and study number	Treatment arms	Estimated enrollment	Primary endpoint
Trastuzumab in combination with targeted therapies
Phase II study of docetaxel, oxaliplatin, capecitabine with bevacizumab and trastuzumab in case of HER2-positivity in patients with locally advanced or metastatic gastric cancer or adenocarcinoma of the gastro-oesophageal junction (B-DOCT study)	Phase II NCT01359397	Docetaxel, oxaliplatin, capecitabine, bevacizumab vs Docetaxel, oxaliplatin, capecitabine, bevacizumab, trastuzumab	Information not available	PFS
A phase II study of afatinib (BIBW 2992) and trastuzumab in patients with advanced HER2-positive trastuzumab-refractory advanced esophagogastric cancer	Phase II NCT01522768	Afatinib (BIBW 2992) + trastuzumab	40	ORR
Intraperitoneal trastuzumab
Phase I trial of intraperitoneal ²¹²Pb-TCMC-trastuzumab for HER-2 expressing malignancy	Phase I NCT01384253	²¹²Pb-TCMC-trastuzumab + trastuzumab	36	Safety
T-DM1
A combination study of kadcyla (trastuzumab emtansine, T-DM1) and capecitabine in patients with HER2-positive metastatic breast cancer and patients with HER2-positive locally advanced/ metastatic gastric cancer (TRAX-HER2 study)[78]	Phase II NCT01702558	Capecitabine + trastuzumab emtansine (T-DM1) vs T-DM1	235	Safety ORR
DS-8201
Phase 1, two-part, multicenter, non-randomized, open-label, multiple dose first-in-human study of DS-8201A, in subjects with advanced solid malignant tumors[36]	Phase II NCT02564900	Trastuzumab deruxtecan (DS-8201a)	198	Safety ORR
Lapatinib
Safety and clinical activity of lapatinib in patients with HER2-positive refractory advanced cancer: a phase II single arm prospective study	Phase II NCT02342587	Lapatinib	25	ORR
New HER2 inhibitors
A phase I-II study to assess the safety, efficacy and pharmacokinetic profile of HM781-36B combined with paclitaxel and trastuzumab in patients with HER-2 positive advanced gastric cancer	Phase I/II NCT01746771	HM781-36B(Poziotinib) (Other Names: NOV120101) + paclitaxel + trastuzumab	48	Safety DLT
A phase 1, dose escalation study of MGAH22 in patients with refractory HER2 positive breast cancer and patients with other HER2 positive carcinomas for whom no standard therapy is available	Phase I NCT01148849	MGAH22 (margetuximab)	67	Safety
A phase I multicenter, open-label, dose-escalation, and dose-expansion study to evaluate the safety, pharmacokinetics, immunogencity, and antitumor activity of MEDI4276 in subjects with select HER2-expressing advanced solid tumors	Phase I NCT02576548	MEDI4276	120	Safety MTD
A phase I study of pyrotinib in combination with docetaxel in patients with HER2 positive advanced gastric cancer	Phase I NCT02378389	Pyrotinib + docetaxel	28	Safety
A two-part phase I, open label, dose escalation study to evaluate the safety, tolerability and pharmacokinetics of pyrotinib in patients whose disease progressed on prior HER2 targeted therapy	Phase I NCT02500199	Pyrotinib	70	Safety MTD
Neratinib
An open-label, multicenter, multinational, phase 2 study exploring the efficacy and safety of neratinib therapy in patients with solid tumors with activating HER2, HER3 or EGFR mutations or with EGFR gene amplification	Phase II NCT01953926	Neratinib	292	ORR
HER2-targeted immunotherapy
A phase Ib/II study of pembrolizumab and monoclonal antibody therapy in patients with advanced cancer (PembroMab)[77]	Phase I/II NCT02318901	Pembrolizumab + trastuzumab vs pembrolizumab + ado-trastuzumab emtansine (T-DM1) vs pembrolizumab + cetuximab	90	Safety and dose-finding
A phase I study to evaluate the antitumor activity and safety of DUKE-002-VRP (HUHER2-ECD + TM), an alphaviral vector encoding the HER2 extracellular domain and transmembrane region, in patient with locally advanced or metastatic human epidermal growth factor receptor 2-positive (HER2+) cancers including breast cancer	Phase I NCT01526473	AVX901	12	Safety
HER2-peptide vaccination of patients with solid tumors	Phase I NCT02276300	Cyclophosphamide sargramostim HER2-Peptid-Vakzine imiquimod	12	Safety

ORR: Overall response rate; HER2: Human epidermal growth factor receptor 2.