Reference Detail

Ref Type Journal Article
PMID (29420467)
Authors Hyman DM, Piha-Paul SA, Won H, Rodon J, Saura C, Shapiro GI, Juric D, Quinn DI, Moreno V, Doger B, Mayer IA, Boni V, Calvo E, Loi S, Lockhart AC, Erinjeri JP, Scaltriti M, Ulaner GA, Patel J, Tang J, Beer H, Selcuklu SD, Hanrahan AJ, Bouvier N, Melcer M, Murali R, Schram AM, Smyth LM, Jhaveri K, Li BT, Drilon A, Harding JJ, Iyer G, Taylor BS, Berger MF, Cutler RE, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB
Title HER kinase inhibition in patients with HER2- and HER3-mutant cancers.
Journal Nature
Vol 554
Issue 7691
Date 2018 Feb 08
URL
Abstract Text Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.

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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
Variant Impact Protein Effect Variant Description Associated with drug Resistance
C544F missense unknown ERBB2 (HER2) C544F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). C544F has been identified in sequencing studies (PMID: 29420467), but has not been biochemically chatacterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
D277G missense unknown ERBB2 (HER2) D277G lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). D277G has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
G778A missense unknown ERBB2 (HER2) G778A lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). G778A has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
K831N missense unknown ERBB2 (HER2) K831N lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). K831N has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
L755_E757delinsS insertion unknown ERBB2 (HER2) L755_E757delinsS results in the deletion of three amino acids from aa 755 to 757 within the protein kinase domain of the Erbb2 (Her2) protein, combined with the insertion of a serine (S) at the same site (UniProt.org). L755_E757delinsS has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
L786V missense unknown ERBB2 (HER2) L786V lies within the protein kinase domain of the Erbb2 (Her2) protein (UniProt.org). L786V has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
P761del deletion unknown ERBB2 (HER2) P761del results in the deletion of one amino acid in the protein kinase domain of the Erbb2 (Her2) protein at amino acid 761 (UniProt.org). P761del has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
R1153* nonsense unknown ERBB2 (HER2) R1153* results in a premature truncation of the Erbb2 (Her2) protein at amino acid 1229 of 1255 (UniProt.org). R1153* has been identified in the scientific literature (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
S250F missense unknown ERBB2 (HER2) S250F lies within the extracellular domain of the Erbb2 (Her2) protein (UniProt.org). S250F has been identified in sequencing studies (PMID: 29420467), but has not been biochemically characterized and therefore, its effect on Erbb2 (Her2) protein function is unknown (PubMed, Apr 2019).
A118V missense unknown SMAD4 A118V lies within the MH1 domain of the Smad4 protein (UniProt.org). A118V has been identified in sequencing studies (PMID: 29420467, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Smad4 protein function is unknown (PubMed, Aug 2018).
D355G missense unknown SMAD4 D355G lies within the MH2 domain of the Smad4 protein (UniProt.org). D355G has been identified in sequencing studies (PMID: 29420467, PMID: 28481359), but has not been biochemically characterized and therefore, its effect on Smad4 protein function is unknown (PubMed, Aug 2018).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
ERBB2 S310F endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 2.6 months in a patient with endometrial cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant Her2-receptor negative breast cancer sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an object response rate of 24% (6/25), a clinical benefit rate of 40% (10/25), and a median progression-free survival of 3.5 months in patients with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F cervical cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response in 1 patient, stable disease in 1 patient, and progressive disease in 1 patient with cervical cancer harboring ERBB2 (HER2) D769N (PMID: 29420467; NCT01953926). 29420467
ERBB2 exon 20 ins lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 10 and progressive disease in 5 of the 15 patients with non-small cell lung cancer harboring ERBB2 (HER2) exon 20 insertion mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 L869R Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 3.6 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L869R (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 6.9 months in a patients with bladder cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant colorectal cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 8.3% (1/12), and a median progression-free survival of 1.8 months in patients with colorectal cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769N cervical cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.5 months in a patient with cervical cancer harboring ERBB2 (HER2) D769N (PMID: 29420467; NCT01953926). 29420467
ERBB2 G776_V777insVGC lung non-small cell carcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 1 patient and progressive disease in 2 patients with non-small cell lung cancer harboring ERBB2 (HER2) G776_V777insVGC (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755P lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 14.8 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755P (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F colorectal cancer conflicting Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with colorectal cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310Y cervical cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 0.5 month in a patient with cervical cancer harboring ERBB2 (HER2) S310Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310Y urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 2 patients and progressive disease in 2 patients with bladder cancer harboring ERBB2 (HER2) S310Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310Y gastroesophageal junction adenocarcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 0.8 month in a patient with gastroesophageal cancer harboring ERBB2 (HER2) S310Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in one patient, and stable disease in 2 patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S biliary tract cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease in one and stable disease in another patient with biliary tract cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 K831N colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with colorectal cancer harboring ERBB2 (HER2) K831N (PMID: 29420467; NCT01953926). 29420467
ERBB2 V697L endometrial cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.6 months in a patient with endometrial cancer harboring ERBB2 (HER2) V697L (PMID: 29420467; NCT01953926). 29420467
ERBB2 L841V Her2-receptor negative breast cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 2.8 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L841V (PMID: 29420467; NCT01953926). 29420467
ERBB2 R678Q gastroesophageal junction adenocarcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) R678Q (PMID: 29420467; NCT01953926). 29420467
ERBB2 V842I colorectal cancer conflicting Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 2 patients and progressive disease in 1 patient with colorectal cancer harboring ERBB2 (HER2) V842I (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769Y urinary bladder cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.4 months in a patient with bladder cancer harboring both ERBB2 (HER2) D769Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S ERBB2 R1153* ERBB2 V777L urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patients with bladder cancer harboring ERBB2 (HER2) L755S, R1153*, and V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 28.6% (2/7), and a median progression-free survival of 2.6 months in patients with endometrial cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L biliary tract cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 3.6 months in one patient, and progressive disease with a progression-free survival of 0.8 months in another patient with biliary tract cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 R678Q colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.6 months in a patient with colorectal cancer harboring ERBB2 (HER2) R678Q (PMID: 29420467; NCT01953926). 29420467
ERBB2 L786V lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.7 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L786V (PMID: 29420467; NCT01953926). 29420467
ERBB2 P761del endometrial cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.9 months in a patient with endometrial cancer harboring ERBB2 (HER2) P761del (PMID: 29420467; NCT01953926). 29420467
ERBB2 V659E lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in two patients with non-small cell lung cancer harboring ERBB2 (HER2) V659E (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup urinary bladder cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patients with bladder cancer harboring ERBB2 (HER2) Y722_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response with a progression-free survival of 14.6 months in one patient, and stable disease with a progression-free survival of 3.7 months in another patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 V659E biliary tract cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 11.1 months in a patient with biliary tract cancer harboring ERBB2 (HER2) V659E (PMID: 29420467; NCT01953926). 29420467
ERBB2 T733I biliary tract cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.7 months in a patient with biliary tract cancer harboring ERBB2 (HER2) T733I (PMID: 29420467; NCT01953926). 29420467
ERBB2 G776delinsVC lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 8.5 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) G776delinsVC (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769H Her2-receptor negative breast cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.5 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) D769H (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L ERBB2 V842I colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.8 months in a patient with colorectal cancer harboring ERBB2 (HER2) V777L and V842I (PMID: 29420467; NCT01953926). 29420467
ERBB2 G778_P780dup lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival over 17 months in 2 patient with non-small cell lung cancer harboring ERBB2 (HER2) G778_P780dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L gastroesophageal junction adenocarcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.1 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in 1 patient, partial response in 1 patient, stable disease in 2 patients, and progressive disease in 4 patients with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 G292R urinary bladder cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with bladder cancer harboring both ERBB2 (HER2) G292R (PMID: 29420467; NCT01953926). 29420467
ERBB2 V842I endometrial cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.8 months in a patient with endometrial cancer harboring ERBB2 (HER2) V842I (PMID: 29420467; NCT01953926). 29420467
ERBB2 D277G ERBB2 S310F urinary bladder cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.7 months in a patient with bladder cancer harboring both ERBB2 (HER2) D277G and S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F biliary tract cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response in one and progressive disease in another patient with biliary tract cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 R678Q endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 5.5 months in a patient with endometrial cancer harboring ERBB2 (HER2) R678Q (PMID: 29420467; NCT01953926). 29420467
ERBB2 G778A colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.9 months in a patient with colorectal cancer harboring ERBB2 (HER2) G778A (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant lung non-small cell carcinoma sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate of 3.8% (1/26), a clinical benefit rate of 42.3% (11/26), and a median progression-free survival of 5.5 months in patients with non-small cell lung cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755A lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.6 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755A (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F gastroesophageal junction adenocarcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 3.9 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 G778_P780dup Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 3.5 months in one patient, and stable disease with a progression-free survival of 20.0 months in another patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) G778_P780dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response in one patient, and progressive disease in 4 patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 18.8% (3/16), and a median progression-free survival of 1.8 months in patients with bladder cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant ovarian cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, no clinical benefit, and a median progression-free survival of 2.1 months in patients with ovarian cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769Y gastroesophageal junction adenocarcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.9 months in a patient with gastroesophageal cancer harboring ERBB2 (HER2) D769Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755_E757delinsS Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 9.0 months in a patient with Erbb2 (Her2) receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) L755_E757delinsS (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant cervical cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate of 20% (1/5), a clinical benefit rate of 60% (3/5), and a median progression-free survival of 20.1 months in patients with cervical cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L colorectal cancer conflicting Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.4 months in a patient with colorectal cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310Y endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 9.6 months in a patient with endometrial cancer harboring ERBB2 (HER2) S310Y (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant biliary tract cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in an objective response rate at 8 weeks of 22.2% (2/9), a clinical benefit rate of 33.3% (3/9), and a median progression-free survival of 2.8 months in patients with biliary tract cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 mutant gastroesophageal junction adenocarcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in no objective response, a clinical benefit rate of 20% (1/5), and a median progression-free survival of 1.7 months in patients with gastroesophageal cancer harboring ERBB2 (HER2) mutations (PMID: 29420467; NCT01953926). 29420467
ERBB2 L841V colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.8 months in a patient with colorectal cancer harboring ERBB2 (HER2) L841V (PMID: 29420467; NCT01953926). 29420467
ERBB2 D769H colorectal cancer predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.9 months in a patient with colorectal cancer harboring ERBB2 (HER2) D769H (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F urinary bladder cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 4 patients and progressive disease in 1 patient with bladder cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 L755S lung non-small cell carcinoma predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in partial response with a progression-free survival of 12.7 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) L755S (PMID: 29420467; NCT01953926). 29420467
ERBB2 V777L endometrial cancer no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease with a progression-free survival of 6.9 months in a patient with endometrial cancer harboring ERBB2 (HER2) V777L (PMID: 29420467; NCT01953926). 29420467
ERBB2 S310F lung non-small cell carcinoma predicted - resistant Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in progressive disease with a progression-free survival of 1.9 months in a patient with non-small cell lung cancer harboring ERBB2 (HER2) S310F (PMID: 29420467; NCT01953926). 29420467
ERBB2 Y772_A775dup lung non-small cell carcinoma no benefit Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in stable disease in 5 patients and progressive disease in 4 patients with non-small cell lung cancer harboring ERBB2 (HER2) Y772_A775dup (PMID: 29420467; NCT01953926). 29420467
ERBB2 exon 20 ins Her2-receptor negative breast cancer predicted - sensitive Neratinib Phase II Actionable In a Phase II trial (SUMMIT), Nerlynx (neratinib) treatment resulted in complete response in 1, partial response in 1, and stable disease in 3 of the 5 patients with Erbb2 (Her2)-receptor negative (non-amplified) breast cancer harboring ERBB2 (HER2) exon 20 insertion mutations (PMID: 29420467; NCT01953926). 29420467