Table 2.

List of selected ongoing clinical trials of anti-HER2 agents in HER2-altered CRC patients

Study	Study title	Regimen	Anti-HER2 agent	Phase	Patient profile	Trial statusa
HER2 amplification/overexpression
TAPUR NCT02693535	Testing the use of FDA-approved drugs that target a specific abnormality in a tumor gene in people with advanced-stage cancer	Trastuzumab plus pertuzumab	mAb	II	HER2 amplification or overexpression	Recruiting
DRUP NCT02925234	The drug rediscovery protocol	Trastuzumab plus pertuzumab	mAb	II	Treatment-refractory HER2-positive mCRC	Recruiting
MOUNTAINEER-03 NCT05253651	A study of tucatinib with trastuzumab and mFOLFOX6 versus standard of care treatment in first-line HER2-positive metastatic colorectal cancer	Tucatinib plus trastuzumab and mFOLFOX6	mAb and TKI	III	HER2-positive mCRC, RAS wt	Recruiting
NCT05673512	To evaluate IAH0968 in combination with CAPEOX in HER2-positive metastatic colorectal cancer	IAH0968 plus CAPEOX	mAb	II/III	HER2 IHC 3 + or 2 + FISH, KRAS, NRAS, BRAF wt	Recruiting
NCT05193292	Camrelizumab combined with trastuzumab and chemotherapy in patients with HER2-positive advanced colorectal cancer	Camrelizumab plus trastuzumab, XELOX, mFOLFOX6, FOLFIRI, mXELIRI and mIRIS	mAb	II	HER2 positivity defined as the colorectal cancer-specific HERACLES diagnostic criteria	Not yet recruiting
NCT05985707	The efficacy and safety of KN026 combination chemotherapy ± KN046 in HER2-positive advanced colorectal cancer and biliary tract cancer as first-line treatment	KN026 plus KN046 and XELOX	Bispecific Ab	II	HER2 IHC 3 + or 2 + /ISH + CRC, RAS, BRAF wt	Not yet recruiting
NCT03929666	A safety and efficacy study of ZW25 (zanidatamab) plus combination chemotherapy in HER2-expressing gastrointestinal cancers, including gastroesophageal adenocarcinoma, biliary tract cancer, and colorectal cancer	Zanidatamab plus capecitabine and cisplatin	Bispecific Ab	II	HER2 IHC 3 + or 2 + /ISH + CRC, RAS, BRAF wt	Active, not recruiting
UNICORN NCT05845450	Pre-operative targeted treatments in molecularly selected resectable colorectal cancer	Trastuzumab deruxtecan	ADC	II	HER2 IHC 3 + or 2 + /ISH + CRC, pMMR/MSS status	Recruiting
NCT05493683	Disitamab vedotin combined with tislelizumab in advanced HER2 positive colorectal cancer	Disitamab vedotin plus tislelizumab	ADC	II	HER2 IHC 3 + or 2 +	Recruiting
NCT05333809	Pembrolizumab and disitamab vedotin in HER2-expressing metastatic colorectal cancer	Disitamab vedotin plus pembrolizumab	ADC	II	HER2 IHC 3 + or 2 + /ISH + CRC, RAS, BRAF wt	Not yet recruiting
NCT05785325	RC48-ADC combined with bevacizumab in HER2-positive advanced colorectal cancer	RC48-ADC plus bevacizumab	ADC	II	HER2 IHC 2 + /FISH positive or IHC3 +	Recruiting
NCT05514717	A study of XMT-2056 in advanced/​recurrent solid tumors that express HER2	XMT-2056	ADC	I	HER2 IHC 3 + or 2 + /ISH + CRC	Recruiting
NCT05382364	Safety and pharmacokinetics of tucatinib (MK-7119) in Chinese participants with cancer	Tucatinib	TKI	I	HER2-positive advanced CRC	Active, not recruiting
NCT05356897	Tucatinib combined with trastuzumab and TAS-102 for the treatment of HER2 positive metastatic colorectal cancer in molecularly selected patients, 3 T Study	Tucatinib plus trastuzumab and TAS-102	TKI and mAb	II	HER2 amplified and PIK3CA, RAS, and/or BRAF-mutated mCRC	Recently withdrawn, completed
NCT06328738	ELVN-002 with trastuzumab + /​- chemotherapy in HER2-positive solid tumors, colorectal and breast cancer	ELVN-002 plus trastuzumab + /​- chemotherapy	TKI and mAb	I	IHC3 + , IHC2 + /ISH + , NGS amplification by tissue, RAS, BRAF wt	Recruiting
NCT04460456	A study of SBT6050 alone and in combination with PD-1 inhibitors in subjects with advanced HER2 expressing solid tumors	SBT6050 plus pembrolizumab and cemiplimab	ADC, immune stimulating	I	Locally advanced or metastatic HER2 IHC 2 + or 3 +	Unknown
NCT04278144	A first-in-human study using BDC-1001 as a single agent and in combination with nivolumab in advanced HER2-expressing solid tumors	BDC-1001	ADC, immune stimulating	I/II	Advanced HER2-expressing solid tumors	Active, not recruiting
VISTA NCT03740256	Binary oncolytic adenovirus in combination with HER2-specific autologous CAR VST, advanced her2 positive solid tumors	HER2 specific CAR T cells plus CAdVEC	HER2 targeting immunotherapy	I	HER2 IHC ≥ 2 +	Recruiting
NCT04660929	CAR macrophages for the treatment of HER2 overexpressing solid tumors	CT-0508	HER2 targeting immunotherapy	I	HER2 overexpression	Active, not recruiting
NCT04319757	ACE1702 in subjects with advanced or metastatic HER2-expressing solid tumors	ACE1702 plus cyclophosphamide and fludarabine	ADC with HER targeting immunotherapy	I	HER2 IHC ≥ 2 +	Recruiting
HER2 amplification/overexpression or mutated HER2
NCT05661357	Disitamab vedotin combined with fruquintinib for mCRC with HER2 expression (HCCSC-C03)	Disitamab vedotin plus fruquintinib	ADC	IV	Advanced CRC with HER2 expression (IHC 1 + , 2 + or 3 +) or mutation detected by NGS	Active, not recruiting
DASH NCT04704661	Testing the combination of two anticancer drugs, DS-8201a and AZD6738, for the treatment of patients with advanced solid tumors expressing the HER2 protein or gene	DS-8201a plus AZD6738	ADC	I	HER2 IHC 1–3 + and FISH	Recruiting
NCT05350917	Study of tislelizumab combined with disitamab vedotin and pyrotinib maleate in HER2-positive or mutated advanced colorectal cancer who failed standard therapy	Tislelizumab plus disitamab vedotin and pyrotinib maleate	ADC	II	HER2 IHC 2 + /FISH positive or IHC3 + or mutation detected by NGS	Not yet recruiting
DETERMINE NCT05786716	Trastuzumab in combination with pertuzumab in adult, teenage/​young adult and pediatric patients with cancers with HER2 amplification or activating mutations	Trastuzumab plus pertuzumab	mAb	II/III	HER2 amplification or activating mutations	Recruiting
TAPUR NCT02693535	TAPUR: Testing the Use of Food and Drug Administration (FDA) approved drugs that target a specific abnormality in a tumor gene in people with advanced-stage cancer	Trastuzumab plus pertuzumab or trastuzumab plus tucatinib	mAb	II	HER2 amplification or overexpression, and specific HER2 mutations	Recruiting
NCT03457896	Study of neratinib + trastuzumab or neratinib + cetuximab in patients with KRAS/​NRAS/​BRAF/​PIK3CA wild-type metastatic colorectal cancer by HER2 status	Neratinib plus trastuzumab or neratinib plus cetuximab	TKI plus mAb	II	KRAS/NRAS/BRAF/PIK3CA wt, mCRC with amplified, non-amplified [wt], or mutated HER2 status	Unknown (was active, not recruiting)
Mutated HER2
DPT01 NCT04639219	A study of T-DXd for the treatment of solid tumors harboring HER2 activating mutations	Trastuzumab deruxtecan	ADC	II	Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations determined by NGS	Active, not recruiting

mAb monoclonal antibody, ADC antibody–drug conjugate, TKI tyrosine kinase inhibitor, NGS next-generation sequencing

^aStatus accurate as of 18 November 2024