Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
NCT ID: NCT01953926
Last Updated: 2024-03-12
Study Results
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View full resultsBasic Information
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TERMINATED
PHASE2
582 participants
INTERVENTIONAL
2013-09-30
2023-01-02
Brief Summary
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Detailed Description
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The trial will consist of a screening period, a treatment period, and an end of treatment visit occurring when neratinib is discontinued for any reason, a safety follow-up visit occurring 28 days after the last dose of neratinib and a survival follow-up period.
Conditions
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Neratinib monotherapy
Neratinib monotherapy in HER2 mutated cancers including cervical, salivary gland, and lung cancers containing EGFR exon 18 mutations.
Cohorts closed to enrollment in prior amendments: HER2 mutant cancers including bladder/urinary, colorectal, endometrial, breast HR-positive, TNBC HR-negative, lung, gastroesophageal, biliary, and ovarian; HER3 mutant solid tumor NOS; HER4 mutant solid tumor NOS; fibrolamellar carcinoma and EGFR brain.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Neratinib and Trastuzumab
Neratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers.
Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Trastuzumab
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
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.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Fulvestrant
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
Trastuzumab
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
Neratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Fulvestrant
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
Trastuzumab
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Neratinib and Paclitaxel
Neratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Paclitaxel
80mg/m\^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
Neratinib and Fulvestrant
Neratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Fulvestrant
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
Interventions
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Neratinib
240 mg administered orally, once daily with food, continuously in 28 day cycles
Fulvestrant
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
Trastuzumab
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
Paclitaxel
80mg/m\^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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
* Prior treatment with any HER2-directed tyrosine kinase inhibitor (e.g., lapatinib, afatinib, dacomitinib, neratinib) is excluded with the following exception: patients with EGFR exon 18 mutated NSCLC who may have received afatinib, osimertinib, or other pan HER or EGFR TKIs remain eligible
* Participants who are receiving any other anticancer agents
* Symptomatic or unstable brain metastases
* Women who are pregnant or breast-feeding
18 Years
ALL
No
Sponsors
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Puma Biotechnology, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Chief Scientific Officer
Role: STUDY_DIRECTOR
Puma Biotechnology, Inc.
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Mayo Clinic Arizona
Phoenix, Arizona, United States
City of Hope
Duarte, California, United States
University of California, San Diego
La Jolla, California, United States
University of Southern California
Los Angeles, California, United States
University of California, Los Angeles
Los Angeles, California, United States
Stanford Cancer Center
Palo Alto, California, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States
Kaiser Permanente NoCal (STRATA)
Vallejo, California, United States
Mayo Clinic Florida
Jacksonville, Florida, United States
University of Miami
Miami, Florida, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States
Northwestern University
Chicago, Illinois, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
Mayo Clinic
Rochester, Minnesota, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States
Washington University
St Louis, Missouri, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, United States
UPMC Magee-Woman's Hospital, Women's Cancer Center
Pittsburgh, Pennsylvania, United States
Saint Francis Cancer Center-Bon Secours
Greenville, South Carolina, United States
The West Clinic
Germantown, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
UT Southwestern Medical Center
Dallas, Texas, United States
MD Anderson Cancer Center
Houston, Texas, United States
Seattle Cancer Care Alliance
Seattle, Washington, United States
Gundersen Center for Cancer and Blood Disorders
La Crosse, Wisconsin, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Peter MacCallum Cancer Centre
East Melbourne, Victoria, Australia
UZ Leuven
Leuven, , Belgium
British Columbia Cancer Center
Vancouver, British Columbia, Canada
University Hospital, Rigshospitalet
Copenhagen, , Denmark
Institut Gustave Roussy
Villejuif, Paris, France
Institut Bergonié
Bordeaux, , France
Centre Leon Berard
Lyon, , France
Institut Curie - Hopital Rene Huguenin
Saint-Cloud, Île-de-France Region, France
St. Vincent's University Hospital
Dublin, Leinster, Ireland
Hadassah Medical Center
Jerusalem, , Israel
Davidoff Cancer Center, Rabin Medical Center
Petah Tikva, , Israel
Sheba Medical Center
Ramat Gan, , Israel
Kaplan Medical Center
Rehovot, , Israel
Sourasky Medical Center
Tel Aviv, , Israel
Azienda Socio Sanitaria Territoriale di Cremona
Cremona, , Italy
Istituto Europeo di Oncologia (IEO) I.R.C.C.S.
Milan, , Italy
Fondazione Policlinico Universitario Gemelli I.R.C.C.S.
Roma, , Italy
AOU Citta della Salute e della Scienza di Torino
Torino, , Italy
Institute for Oncology and Radiology of Serbia
Belgrade, , Serbia
Yonsei University Health System, Serverance Hospital
Seodaemun-Gu, Seoul, South Korea
Hospital Universitario Quiron Dexeus
Barcelona, , Spain
Hospital Universitario Vall d'Hebron
Barcelona, , Spain
Hospital Universitari Clinic Barcelona
Barcelona, , Spain
Hospital Clinico Universitario San Carlos
Madrid, , Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, , Spain
Hospital Universitario Madrid Sanchinarro (START Madrid)
Madrid, , Spain
Hospital Universitario Quiron Madrid
Madrid, , Spain
Instituto Valenciano de Oncologia
Valencia, , Spain
Hospital Clinico Universitario de Valencia
Valencia, , Spain
Royal Free Hospital
London, , United Kingdom
Countries
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References
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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. doi: 10.1038/nature25475. Epub 2018 Jan 31.
Smyth LM, Piha-Paul SA, Won HH, Schram AM, Saura C, Loi S, Lu J, Shapiro GI, Juric D, Mayer IA, Arteaga CL, de la Fuente MI, Brufksy AM, Spanggaard I, Mau-Sorensen M, Arnedos M, Moreno V, Boni V, Sohn J, Schwartzberg LS, Gonzalez-Farre X, Cervantes A, Bidard FC, Gorelick AN, Lanman RB, Nagy RJ, Ulaner GA, Chandarlapaty S, Jhaveri K, Gavrila EI, Zimel C, Selcuklu SD, Melcer M, Samoila A, Cai Y, Scaltriti M, Mann G, Xu F, Eli LD, Dujka M, Lalani AS, Bryce R, Baselga J, Taylor BS, Solit DB, Meric-Bernstam F, Hyman DM. Efficacy and Determinants of Response to HER Kinase Inhibition in HER2-Mutant Metastatic Breast Cancer. Cancer Discov. 2020 Feb;10(2):198-213. doi: 10.1158/2159-8290.CD-19-0966. Epub 2019 Dec 5.
Friedman CF, D'Souza A, Bello Roufai D, Tinker AV, de Miguel M, Gambardella V, Goldman J, Loi S, Melisko ME, Oaknin A, Spanggaard I, Shapiro GI, ElNaggar AC, Panni S, Ravichandran V, Frazier AL, DiPrimeo D, Eli LD, Solit DB. Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial. Gynecol Oncol. 2024 Feb;181:162-169. doi: 10.1016/j.ygyno.2023.12.004. Epub 2024 Jan 11.
Jhaveri K, Eli LD, Wildiers H, Hurvitz SA, Guerrero-Zotano A, Unni N, Brufsky A, Park H, Waisman J, Yang ES, Spanggaard I, Reid S, Burkard ME, Vinayak S, Prat A, Arnedos M, Bidard FC, Loi S, Crown J, Bhave M, Piha-Paul SA, Suga JM, Chia S, Saura C, Garcia-Saenz JA, Gambardella V, de Miguel MJ, Gal-Yam EN, Rapael A, Stemmer SM, Ma C, Hanker AB, Ye D, Goldman JW, Bose R, Peterson L, Bell JSK, Frazier A, DiPrimeo D, Wong A, Arteaga CL, Solit DB. Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial. Ann Oncol. 2023 Oct;34(10):885-898. doi: 10.1016/j.annonc.2023.08.003. Epub 2023 Aug 18.
Harding JJ, Piha-Paul SA, Shah RH, Murphy JJ, Cleary JM, Shapiro GI, Quinn DI, Brana I, Moreno V, Borad M, Loi S, Spanggaard I, Park H, Ford JM, Arnedos M, Stemmer SM, de la Fouchardiere C, Fountzilas C, Zhang J, DiPrimeo D, Savin C, Duygu Selcuklu S, Berger MF, Eli LD, Meric-Bernstam F, Jhaveri K, Solit DB, Abou-Alfa GK. Antitumour activity of neratinib in patients with HER2-mutant advanced biliary tract cancers. Nat Commun. 2023 Feb 6;14(1):630. doi: 10.1038/s41467-023-36399-y.
Shishido SN, Masson R, Xu L, Welter L, Prabakar RK, D' Souza A, Spicer D, Kang I, Jayachandran P, Hicks J, Lu J, Kuhn P. Disease characterization in liquid biopsy from HER2-mutated, non-amplified metastatic breast cancer patients treated with neratinib. NPJ Breast Cancer. 2022 Feb 18;8(1):22. doi: 10.1038/s41523-022-00390-5.
Oaknin A, Friedman CF, Roman LD, D'Souza A, Brana I, Bidard FC, Goldman J, Alvarez EA, Boni V, ElNaggar AC, Passalacqua R, Do KTM, Santin AD, Keyvanjah K, Xu F, Eli LD, Lalani AS, Bryce RP, Hyman DM, Meric-Bernstam F, Solit DB, Monk BJ. Neratinib in patients with HER2-mutant, metastatic cervical cancer: Findings from the phase 2 SUMMIT basket trial. Gynecol Oncol. 2020 Oct;159(1):150-156. doi: 10.1016/j.ygyno.2020.07.025. Epub 2020 Jul 25.
Ulaner GA, Saura C, Piha-Paul SA, Mayer I, Quinn D, Jhaveri K, Stone B, Shahin S, Mann G, Dujka M, Bryce R, Meric-Bernstam F, Solit DB, Hyman DM. Impact of FDG PET Imaging for Expanding Patient Eligibility and Measuring Treatment Response in a Genome-Driven Basket Trial of the Pan-HER Kinase Inhibitor, Neratinib. Clin Cancer Res. 2019 Dec 15;25(24):7381-7387. doi: 10.1158/1078-0432.CCR-19-1658. Epub 2019 Sep 23.
Hanker AB, Brewer MR, Sheehan JH, Koch JP, Sliwoski GR, Nagy R, Lanman R, Berger MF, Hyman DM, Solit DB, He J, Miller V, Cutler RE Jr, Lalani AS, Cross D, Lovly CM, Meiler J, Arteaga CL. An Acquired HER2T798I Gatekeeper Mutation Induces Resistance to Neratinib in a Patient with HER2 Mutant-Driven Breast Cancer. Cancer Discov. 2017 Jun;7(6):575-585. doi: 10.1158/2159-8290.CD-16-1431. Epub 2017 Mar 8.
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form: Breast
Document Type: Informed Consent Form: Neratinib Monotherapy
Related Links
Access external resources that provide additional context or updates about the study.
HER Kinase Inhibition in Patients With HER2- And HER3-mutant Cancers
Efficacy and Determinants of Response to HER Kinase Inhibition in HER2 -Mutant Metastatic Breast Cancer
Other Identifiers
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2013-002872-42
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PUMA-NER-5201
Identifier Type: -
Identifier Source: org_study_id
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