Malignant solid neoplasm, ERBB2-mutated

4 regimens on this page 4 variants on this page

All lines of therapy

Neratinib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Hyman et al. 2018 (SUMMITHER)	NR to 2016-12-16	Non-randomized basket trial

Note: the cycle length is not described in the manuscript; the authors have clarified that the cycles are 28 days in length. This trial should not be confused with the one by the same name in multiple myeloma.

Biomarker eligibility criteria

• Gene: HER2
• Alteration: various substitutions, insertions, frameshifts, or structural variants
• Acceptable methods of measurement: next-generation sequencing assay or RT-PCR, Sanger, pyrosequencing, or mass spectrometry-based sequencing methods

Prior treatment criteria

• No prior treatment with HER kinase inhibitors

Targeted therapy

• Neratinib (Nerlynx) 240 mg PO once per day on days 1 to 28

Supportive therapy

• Loperamide (Imodium) (dose not specified) mandatory during cycle 1

28-day cycles

References

1. SUMMIT: 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 Jr, Xu F, Butturini A, Eli LD, Mann G, Farrell C, Lalani AS, Bryce RP, Arteaga CL, Meric-Bernstam F, Baselga J, Solit DB. HER kinase inhibition in patients with HER2- and HER3-mutant cancers. Nature. 2018 Feb 8;554(7691):189-194. Epub 2018 Jan 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01953926

Pertuzumab & Trastuzumab

Regimen

Study	Dates of enrollment	Evidence
Hainsworth et al. 2018 (MyPathway)	2014-2016	Phase 2a

Biomarker eligibility criteria

• Gene: HER2
• Alteration: amplification or activation (including exon 20 insertions, deletions around amino acids 755 to 759, and nonsynonymous amino acid substitutions)
• Acceptable methods of measurement: molecular profiling performed on tissue obtained at the most recent tumor biopsy

Targeted therapy

• Pertuzumab (Perjeta) as follows:
  • Cycle 1: 840 mg IV once on day 1
  • Cycle 2 onwards: 420 mg IV once on day 1
• Trastuzumab (Herceptin) as follows:
  • Cycle 1: 8 mg/kg IV once on day 1
  • Cycle 2 onwards: 6 mg/kg IV once on day 1

21-day cycles

References

1. MyPathway: Hainsworth JD, Meric-Bernstam F, Swanton C, Hurwitz H, Spigel DR, Sweeney C, Burris H, Bose R, Yoo B, Stein A, Beattie M, Kurzrock R. Targeted therapy for advanced solid tumors on the basis of molecular profiles: results from MyPathway, an open-label, phase IIa multiple basket study. J Clin Oncol. 2018 Feb 20;36(6):536-542. Epub 2018 Jan 10. link to original article contains dosing details in manuscript PubMed NCT02091141
   1. Update: Sweeney CJ, Hainsworth JD, Bose R, Burris HA, Kurzrock R, Swanton C, Friedman CF, Spigel DR, Szado T, Schulze K, Price R, Malato J, Lo AA, Levy J, Wang Y, Yu W, Meric-Bernstam F. MyPathway Human Epidermal Growth Factor Receptor 2 Basket Study: Pertuzumab + Trastuzumab Treatment of a Tissue-Agnostic Cohort of Patients With Human Epidermal Growth Factor Receptor 2-Altered Advanced Solid Tumors. J Clin Oncol. 2024 Jan 20;42(3):258-265. Epub 2023 Oct 4. link to original article PubMed

Trastuzumab deruxtecan monotherapy

Regimen

Study	Dates of enrollment	Evidence
Meric-Bernstam et al. 2023 (DESTINY-PanTumo02)	2020-10-07 to 2022-07-07	Phase 2 (RT)

Antibody-drug conjugate therapy

• Trastuzumab deruxtecan (Enhertu) 5.4 mg/kg IV once on day 1

21-day cycles

References

1. DESTINY-PanTumor02: Meric-Bernstam F, Makker V, Oaknin A, Oh DY, Banerjee S, González-Martín A, Jung KH, Ługowska I, Manso L, Manzano A, Melichar B, Siena S, Stroyakovskiy D, Fielding A, Ma Y, Puvvada S, Shire N, Lee JY. Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial. J Clin Oncol. 2024 Jan 1;42(1):47-58. Epub 2023 Oct 23. link to original article link to PMC article contains dosing details in abstract PubMed NCT04482309

Trastuzumab emtansine monotherapy

Regimen

Study	Dates of enrollment	Evidence
Li et al. 2018 (MSK 15-335)	2016-03 to 2016-12	Phase 2 basket trial, fewer than 20 pts reported to date

Note: only partial results have been published to date.

Biomarker eligibility criteria

• Gene: HER2
• Alteration: various exon 20 insertions, single-base pair substitutions, or other likely activating mutations
• Acceptable methods of measurement: next-generation sequencing

Antibody-drug conjugate therapy

• Trastuzumab emtansine (Kadcyla) 3.6 mg/kg IV once on day 1

21-day cycles

References

1. MSK 15-335: Li BT, Shen R, Buonocore D, Olah ZT, Ni A, Ginsberg MS, Ulaner GA, Offin M, Feldman D, Hembrough T, Cecchi F, Schwartz S, Pavlakis N, Clarke S, Won HH, Brzostowski EB, Riely GJ, Solit DB, Hyman DM, Drilon A, Rudin CM, Berger MF, Baselga J, Scaltriti M, Arcila ME, Kris MG. Ado-trastuzumab emtansine for patients with HER2-mutant lung cancers: results from a phase II basket trial. J Clin Oncol. 2018 Aug 20;36(24):2532-2537. Epub 2018 Jul 10. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02675829