Clinical Trial - NCT01953926

Neratinib HER Mutation Basket Study


Sponsor: Puma Biotechnology, Inc.


Information provided by (Responsible party): Sponsor Identifier: NCT01953926

Protocol Info

Short Description: Phase II of Neratinib in AST with EGFR, HER2 and HER3 mutations or EGFR Gene Amplification
Long Description: An Open-Label, Phase 2 Study of Neratinib in Patients with Solid Tumors with Somatic Human Epidermal Growth Factor Receptor (EGFR, HER2, HER3) Mutations or EGFR Gene Amplification
MGH Status: Open
Sponsor: Puma Biotechnology
Disease Program: Phase I

Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation.


This is an open-label, multicenter, multinational, Phase 2 basket study exploring the efficacy and safety of neratinib as monotherapy or in combination with other therapies in participants with HER (EGFR, HER2) mutation-positive solid tumors.
Condition Title Intervention Phase
Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations Neratinib Paclitaxel Fulvestrant Trastuzumab Phase 2
Study Type Interventional
Official Title An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations

Primary Outcome Measures

Confirmed Objective Response Rate (Breast, Cervical Cohorts) [Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months] [Designated as safety issue: ]

Objective Response Rate - First Tumor Assessment (Other Cohorts) [Time Frame: From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks] [Designated as safety issue: ]

Secondary Outcome Measures

Progression-Free Survival (PFS) [Time Frame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 18 months] [Designated as safety issue: ]

Confirmed Objective Response Rate (Other Cohorts) [Time Frame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, up to 18 months] [Designated as safety issue: ]

Objective Response Rate - First Tumor Assessment (Breast, Cervical Cohorts) [Time Frame: From enrollment date to first Complete or Partial Response, whichever came earlier, up to 8 or 9 weeks] [Designated as safety issue: ]

Clinical Benefit Rate (CBR) [Time Frame: From enrollment date to first documented response or stable disease =16, or =24 weeks for breast cancer, assessed up to 18 months] [Designated as safety issue: ]

Duration of Response (DOR) [Time Frame: From first response to first disease progression or death, assessed up to 18 months] [Designated as safety issue: ]

Overall Survival (OS) [Time Frame: From enrollment date to death, assessed up to two years] [Designated as safety issue: ]

Incidence of Treatment-Emergent Adverse Events [Time Frame: From first dose through 28 days after the last dose, assessed up to 18 months] [Designated as safety issue: ]

Estimated Enrollment: 650
Study Start Date: September 2013
Estimated Study Completion Date: March 2022
Estimated Primary Completion Date: September 2021
Arms Assigned Interventions

Experimental:Neratinib monotherapy

Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, solid tumors (NOS) and lung cancers containing EGFR exon 18 mutations. Cohorts closed to enrollment in Amendment 6: gastroesophageal, biliary, ovarian, solid tumor (NOS) HER4 mutant, and fibrolamellar carcinoma.

Experimental:Neratinib and Paclitaxel

Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
80mg/m^2 administered IV on Days 1, 8, and 15 of every 4 week cycle

Experimental:Neratinib and Trastuzumab

Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in Amendment 6: colorectal, lung cancer HER2 mutant.
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter

Experimental:Neratinib, Fulvestrant and Trastuzumab (Randomized)

Neratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.

Experimental:Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)

Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with CDK4/6i naïve) breast cancers.
500 mg administered as two 5 mL injections on Days 1, 15, and 29; then once every 4 weeks thereafter month, then Day 1 of every 4 week cycle


Ages Eligible for Study: N/A-N/A

Genders Eligible for Study: All

Accepts Healthly Volunteers: No

Inclusion Criteria:

  • Provide written informed consent
  • Histologically confirmed cancers for which no curative therapy exists
  • Documented HER2 or EGFR exon 18 mutation
  • Participants must agree and commit to use appropriate methods of contraception as outlined in the protocol
  • At least one measurable lesion, defined by RECIST v1.1

Exclusion Criteria:

  • Participants harboring ineligible somatic HER2 mutations
  • Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib, tucatinib, poziotinib)
  • Participants who are receiving any other anticancer agents
  • Symptomatic or unstable brain metastases
  • Women who are pregnant or breast-feeding

There are additional inclusion and exclusion criteria. The study center will determine if criteria for participation are met.

Contacts and Locations

Please refer to this study by its identifier: NCT01953926


  • United States, Alabama
    • University of Alabama at Birmingham Birmingham, Alabama, United States, 35249
  • United States, Arizona
    • Mayo Clinic Arizona Phoenix, Arizona, United States, 85054
  • United States, California
    • City of Hope Duarte, California, United States, 91010
    • University of California, San Diego La Jolla, California, United States, 92093
    • University of Southern California Los Angeles, California, United States, 90089
    • University of California, Los Angeles Los Angeles, California, United States, 90095
    • Stanford Cancer Center Palo Alto, California, United States, 94304
    • UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California, United States, 94115
    • Kaiser Permanente NoCal (STRATA) Vallejo, California, United States, 94589
  • United States, Delaware
    • Christiana Care Health Services, Christiana Hospital Newark, Delaware, United States, 19718
  • United States, Florida
    • Mayo Clinic Florida Jacksonville, Florida, United States, 32224
    • University of Miami Miami, Florida, United States, 33136
  • United States, Georgia
    • Winship Cancer Institute, Emory University Atlanta, Georgia, United States, 30322
  • United States, Illinois
    • Northwestern University Chicago, Illinois, United States, 60611
  • United States, Louisiana
    • Ochsner Clinic Foundation New Orleans, Louisiana, United States, 70121
  • United States, Massachusetts
    • Dana Farber Cancer Institute Boston, Massachusetts, United States, 02215
  • United States, Michigan
    • University of Michigan Ann Arbor, Michigan, United States, 48109
  • United States, Minnesota
    • Mayo Clinic Rochester, Minnesota, United States, 55905
    • Metro Minnesota Community Oncology Research Consortium Saint Louis Park, Minnesota, United States, 55416
  • United States, Missouri
    • Washington University Saint Louis, Missouri, United States, 63110
  • United States, New Jersey
    • Rutgers Cancer Institute of New Jersey New Brunswick, New Jersey, United States, 08903
  • United States, New York
    • Roswell Park Comprehensive Cancer Center Buffalo, New York, United States, 14263
    • Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10065
  • United States, Ohio
    • Kettering Medical Center Kettering, Ohio, United States, 45429
  • United States, Pennsylvania
    • UPMC Magee-Woman's Hospital, Women's Cancer Center Pittsburgh, Pennsylvania, United States, 15213
    • Abington Memorial Hospital, Asplundh Cancer Pavilion Willow Grove, Pennsylvania, United States, 19090
  • United States, South Carolina
    • Saint Francis Cancer Center-Bon Secours Greenville, South Carolina, United States, 29607
  • United States, Tennessee
    • The West Clinic Germantown, Tennessee, United States, 38138
    • Vanderbilt-Ingram Cancer Center Nashville, Tennessee, United States, 37232
  • United States, Texas
    • UT Southwestern Medical Center Dallas, Texas, United States, 75390
    • MD Anderson Cancer Center Houston, Texas, United States, 77030
  • United States, Wisconsin
    • Gundersen La Crosse, Wisconsin, United States, 54601
    • University of Wisconsin Carbone Cancer Center Madison, Wisconsin, United States, 53792
  • Australia, Victoria
    • Peter MacCallum Cancer Centre East Melbourne, Victoria, Australia, 8006
  • Belgium,
    • UZ Leuven Leuven, , Belgium, 3000
  • Canada, British Columbia
    • British Columbia Cancer Center Vancouver, British Columbia, Canada, V5Z 4E6
  • Denmark,
    • University Hospital, Rigshospitalet Kopenhagen, , Denmark, DK-2100
  • Finland,
    • Helsinki University Central Hospital Helsinki, , Finland, 00029
  • France, Ile De France
    • Institut Curie - Hopital Rene Huguenin Saint-Cloud, Ile De France, France, 92210
  • France, Paris
    • Institut Gustave Roussy Villejuif, Paris, France, 94800
  • France,
    • Centre Leon Berard Lyon, , France, 69393
  • Ireland, Cork
    • Cork University Hospital Wilton, Cork, Ireland, T12 DC4A
  • Ireland, Leinster
    • St. Vincent's University Hospital Dublin, Leinster, Ireland, D04 T6F4
  • Israel,
    • Hadassah Medical Center Jerusalem, , Israel, 9112001
    • Davidoff Cancer Center, Rabin Medical Center Petah Tikva, , Israel, 4941494
    • Sheba Medical Center Ramat Gan, , Israel, 5262000
    • Kaplan Medical Center Rehovot, , Israel, 7661041
    • Sourasky Medical Center Tel Aviv, , Israel, 6423906
  • Italy,
    • Azienda Socio Sanitaria Territoriale di Cremona Cremona, , Italy, 26100
    • Instituto Nazionale dei Tumori Fond Pascale IRCCS Napoli, , Italy, 80131
    • AOU Citta della Salute e della Scienza di Torino Torino, , Italy, 10126
  • Korea, Republic of, Seoul
    • Yonsei University Health System, Serverance Hospital Seodaemun-Gu, Seoul, Korea, Republic of, 120-752
  • Serbia,
    • Institute for Oncology and Radiology of Serbia Belgrade, , Serbia, 11000
  • Spain,
    • Hospital Universitario Quiron Dexeus Barcelona, , Spain, 08028
    • Hospital Universitario Vall d'Hebron Barcelona, , Spain, 08035
    • Hospital Universitari Clinic Barcelona Barcelona, , Spain, 08036
    • Hospital Clinico Universitario San Carlos Madrid, , Spain, 28040
    • Hospital Universitario Fundacion Jimenez Diaz Madrid, , Spain, 28040
    • Hospital Universitario Madrid Sanchinarro (START Madrid) Madrid, , Spain, 28050
    • Hospital Universitario Quiron Madrid Madrid, , Spain, 28223
    • Instituto Valenciano de Oncologia Valencia, , Spain, 46009
    • Hospital Clinico Universitario de Valencia Valencia, , Spain, 46010
  • United Kingdom,
    • University College London Hospitals NHS Foundation Trust London, , United Kingdom, NW1 2BU
    • Royal Free Hospital London, , United Kingdom, NW3 2QG

Sponsors and Collaborators

Puma Biotechnology, Inc.

More Information

No publications provided

Responsible Party: Sponsor Identifier: NCT01953926
Other Study ID Numbers: 2013-002872-42
Study First Received:
Last Updated:
Health Authority:

Keywords provided by Puma Biotechnology, Inc.:




Solid Tumors


HER2 mutations

EGFR mutations

Bladder/Urinary Tract






Additional relevant MeSH terms:




Next Steps

If you are interested in this protocol or in other treatment options at Massachusetts General Hospital, please Request a Consultation. processed this data on February 25, 2021