Table 1.

Summary of efficacy outcomes of HER2 therapies in refractory HER2 positive mCRC

Study	Regimen	Phase	N	ORR	Eligibility criteria	Median PFS months (95% CI)	Median OS Months (95% CI)	Trial statusa	References
Monoclonal antibody (mAb)
MYPATHWAYb NCT02091141	Trastuzumab plus pertuzumab	II	69	31.9%	HER2 overexpression and/or amplification	4.1 (2.7 to 5.6) months	15.5 (10.3 to 20.9) months	Completed	[40]
TAPUR NCT02693535	Trastuzumab plus pertuzumab	II	28	25%	HER2 amplification or overexpression	17.2 (11.1 to 27.4) weeks	60.0 (32.1 to 102.3) weeks	Recruiting	[41]
TRIUMPH UMIN000027887	Trastuzumab plus pertuzumab	II	17	35%	HER2-positive mCRC, IHC 3 + , RAS wt	4.0 (1.4 to 5.6) months	NR	Unknown	[42]
Meric Bernstam et al., 2022 NCT02892123	Zanidatamab	I	26	38%	HER2 IHC 3 + or 2 + /ISH, KRAS wt	6.8 (3.5 to 7.8) months	NR	Active, not recruiting	[43]
NCT03185988	Trastuzumab plus irinotecan	II	21	33.3%	HER2 IHC 3 + or 2 + proven by FISH, SISH or CISH, KRAS/NRAS/BRAF wt	4.3 (2.7 to 5.9) months	17.9 (11.8 to 24.1) months	Unknown	[44]
Antibody drug conjugates (ADC)
DESTINY-CRC01 NCT03384940	T-DXd	II	53	45.3%	HER2 IHC 3 + or 2 + /ISH positive, RAS/BRAF wt, Chemotherapy refractory	6.9 (4.1 to 8.7) months	15.5 (8.8 to 20.8) months	Completed	[45]
DESTINY-CRC02 NCT04744831	T-DXd	II	82	37.8%c	HER2 IHC 3 + or 2 + /ISH positive, BRAF wt	5.8 (4.6 to 7.0) monthsc	NR	Completed	[11]
HERACLES-B NCT03225937	T-DM1 plus pertuzumab	II	31	9.7%	HERACLES diagnostic criteria by IHC and FISH, RAS wt	4.1 (3.6 to 5.9) months	NR	Completed	[46]
NCT04513223	Trastuzumab rezetecan	I	32	46.9%	HER2-expressing advanced/unresectable or metastatic CRC	2.9 (1.5 to 7.1) monthsd	NR	Active, not recruiting	[47]
Tyrosine kinase inhibitor (TKI)-containing regimens
HERACLES-A NCT03225937	Trastuzumab plus lapatinib	II	32	28%	HERACLES diagnostic criteria by IHC and FISH, KRAS wt	4.7 (3.7 to 6.1) months	10.0 (7.9 to 15.8) months	Unknown	[48]
MOUNTAINEER NCT03043313	Tucatinib with or without trastuzumab	II	84	Tucatinib plus trastuzumab: 38.1%, Tucatinib alone: 3.3%	HER2 IHC 3 + or 2 + /ISH positive, RAS wt	tucatinib plus trastuzumab: 8.2 (4.2 to 10.3) months, tucatinib alone: NR	Tucatinib plus trastuzumab: 24.1 (20.3 to 36.7) months, tucatinib alone: NR	Completed	[49]
HER2-FUSCC-G NCT04960943	Pyrotinib plus trastuzumab	II	16	50.0%	HERACLES diagnostic criteria for HER2-positive mCRC with at least two prior lines of treatment	7.53 (5.19 to 9.87) months	16.8 (8.72 to 24.87) months	Unknown	[50]
Fu et al., 2023 NCT04380012	Pyrotinib plus trastuzumab	II	18	22.2%	HER2 IHC 3 + or 2 + /SISH or FISH, BRAF wt	3.4 (1.8 to 4.3) months	Not reached	Unknown	[51]

HER2 human epidermal growth factor receptor 2, ORR objective response rate, PFS progression free survival, OS overall survival, wt wild-type, IHC immunohistochemistry, ISH in situ hybridization, FISH fluorescent in situ hybridization, SISH silver in situ hybridization, CISH chromogenic in situ hybridization, ctDNA circulating tumor deoxyribonucleic acid, NR not reported, T-DXd trastuzumab deruxtecan; T-DM1 trastuzumab emtansine

^aStatus accurate as of 18 November 2024

^bPatients with HER2 amplification/overexpression and wild-type KRAS

^cPatients who received 5.4 mg/kg T-DXd dose

^dTime to recurrence (TTR), median range