Study Stopped
The study was terminated to align with the sponsor's current development plans for neratinib. The decision was not based on any new efficacy or safety data for neratinib.
Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
SUMMIT
An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
2 other identifiers
interventional
582
13 countries
60
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2013
Longer than P75 for phase_2
60 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2013
CompletedStudy Start
First participant enrolled
September 30, 2013
CompletedFirst Posted
Study publicly available on registry
October 1, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 2, 2023
CompletedStudy Completion
Last participant's last visit for all outcomes
January 2, 2023
CompletedResults Posted
Study results publicly available
March 12, 2024
CompletedMarch 12, 2024
February 1, 2024
9.3 years
September 26, 2013
December 21, 2023
February 12, 2024
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
Percentage of participants who are confirmed by independent central review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (HR+, HER2 negative metastatic breast cancer cohorts). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort)
Percentage of participants who are confirmed by investigator review to have achieved complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (cervical cancer cohort). Per Response Evaluation Criteria in Sold Tumors Criteria (RECISTv1.1) for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts)
Percentage of participants who achieve CR or PR per Response Evaluation Criteria in Sold Tumors Criteria (RECIST) v1.1, or other defined response criteria, at the first scheduled tumor assessment (all other cohorts), per RECIST (if assessed) or PERCIST. RECISTv1.1 for target lesions and assessed by MRI or CT: Complete response(CR),Disappearance of all target lesions; Partial response(PR),\>=30% decrease in sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR PERCISTv1.0: Complete Metabolic Response - Complete resolution of 18F-FDG uptake within measurable target lesion so that it is less than mean liver activity and indistinguishable from surrounding background blood-pool levels Partial Metabolic Response - Reduction of minimum of 30% in target measurable tumour 18F-FDG SULpeak. Absolute drop in SUL must be at least 0.8 SUL units, as well. No new lesions. Positive Metabolic Response - Participants having either "Complete Metabolic Response" or "Part
From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks
Secondary Outcomes (9)
Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort)
From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts)
From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months.
Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
From first response to first disease progression or death, assessed up to 58 months
Duration of Response (DOR) by Investigator Review (All Cohorts)
From first response to first disease progression or death, assessed up to 58 months
Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months
- +4 more secondary outcomes
Study Arms (6)
Neratinib monotherapy
EXPERIMENTALNeratinib 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 and Trastuzumab
EXPERIMENTALNeratinib and Trastuzumab in HER2 mutated (TNBC, HR-negative) breast cancers. Cohorts closed to enrollment in in prior amendments: colorectal, lung cancer HER2 mutant.
Neratinib, Fulvestrant and Trastuzumab (Randomized)
EXPERIMENTALNeratinib, Fulvestrant and Trastuzumab or Fulvestrant and Trastuzumab or Fulvestrant alone in HER2 mutated (HR-positive with prior CDK4/6i) breast cancers.
Neratinib, Fulvestrant and Trastuzumab (Non-Randomized)
EXPERIMENTALNeratinib, Fulvestrant and Trastuzumab in HER2 mutated (HR-positive with or without CDK4/6i) breast cancers.
Neratinib and Paclitaxel
EXPERIMENTALNeratinib and Paclitaxel in HER2 mutated bladder/urinary tract cancers.
Neratinib and Fulvestrant
EXPERIMENTALNeratinib and Fulvestrant in HER2 mutated (HR-positive) breast cancers.
Interventions
240 mg administered orally, once daily with food, continuously in 28 day cycles
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
Initial dose of 8 mg/kg of trastuzumab administered IV on Day 1, followed by 6 mg/kg IV once every 3 weeks thereafter
80mg/m\^2 administered IV on Days 1, 8, and 15 of every 4 week cycle
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Participants harboring ineligible somatic HER2 mutations
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (60)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
Mayo Clinic Arizona
Phoenix, Arizona, 85054, United States
City of Hope
Duarte, California, 91010, United States
University of California, San Diego
La Jolla, California, 92093, United States
University of Southern California
Los Angeles, California, 90089, United States
University of California, Los Angeles
Los Angeles, California, 90095, United States
Stanford Cancer Center
Palo Alto, California, 94304, United States
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115, United States
Kaiser Permanente NoCal (STRATA)
Vallejo, California, 94589, United States
Mayo Clinic Florida
Jacksonville, Florida, 32224, United States
University of Miami
Miami, Florida, 33136, United States
Winship Cancer Institute, Emory University
Atlanta, Georgia, 30322, United States
Northwestern University
Chicago, Illinois, 60611, United States
Ochsner Clinic Foundation
New Orleans, Louisiana, 70121, United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Mayo Clinic
Rochester, Minnesota, 55905, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Washington University
St Louis, Missouri, 63110, United States
Roswell Park Comprehensive Cancer Center
Buffalo, New York, 14263, United States
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065, United States
UPMC Magee-Woman's Hospital, Women's Cancer Center
Pittsburgh, Pennsylvania, 15213, United States
Saint Francis Cancer Center-Bon Secours
Greenville, South Carolina, 29607, United States
The West Clinic
Germantown, Tennessee, 38138, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
MD Anderson Cancer Center
Houston, Texas, 77030, United States
Seattle Cancer Care Alliance
Seattle, Washington, 98109, United States
Gundersen Center for Cancer and Blood Disorders
La Crosse, Wisconsin, 54601, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792, United States
Peter MacCallum Cancer Centre
East Melbourne, Victoria, 8006, Australia
UZ Leuven
Leuven, 3000, Belgium
British Columbia Cancer Center
Vancouver, British Columbia, V5Z 4E6, Canada
University Hospital, Rigshospitalet
Copenhagen, DK-2100, Denmark
Institut Gustave Roussy
Villejuif, Paris, 94800, France
Institut Bergonié
Bordeaux, 33076, France
Centre Leon Berard
Lyon, 69393, France
Institut Curie - Hopital Rene Huguenin
Saint-Cloud, Île-de-France Region, 92210, France
St. Vincent's University Hospital
Dublin, Leinster, D04 T6F4, Ireland
Hadassah Medical Center
Jerusalem, 9112001, Israel
Davidoff Cancer Center, Rabin Medical Center
Petah Tikva, 4941494, Israel
Sheba Medical Center
Ramat Gan, 5262000, Israel
Kaplan Medical Center
Rehovot, 7661041, Israel
Sourasky Medical Center
Tel Aviv, 6423906, Israel
Azienda Socio Sanitaria Territoriale di Cremona
Cremona, 26100, Italy
Istituto Europeo di Oncologia (IEO) I.R.C.C.S.
Milan, 20141, Italy
Fondazione Policlinico Universitario Gemelli I.R.C.C.S.
Roma, 00168, Italy
AOU Citta della Salute e della Scienza di Torino
Torino, 10126, Italy
Institute for Oncology and Radiology of Serbia
Belgrade, 11000, Serbia
Yonsei University Health System, Serverance Hospital
Seodaemun-Gu, Seoul, 120-752, South Korea
Hospital Universitario Quiron Dexeus
Barcelona, 08028, Spain
Hospital Universitario Vall d'Hebron
Barcelona, 08035, Spain
Hospital Universitari Clinic Barcelona
Barcelona, 08036, Spain
Hospital Clinico Universitario San Carlos
Madrid, 28040, Spain
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040, Spain
Hospital Universitario Madrid Sanchinarro (START Madrid)
Madrid, 28050, Spain
Hospital Universitario Quiron Madrid
Madrid, 28223, Spain
Instituto Valenciano de Oncologia
Valencia, 46009, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
Royal Free Hospital
London, NW3 2QG, United Kingdom
Related Publications (10)
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.
PMID: 29420467BACKGROUNDSmyth 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.
PMID: 31806627BACKGROUNDLi BT, Gandhi L, Ravichandran V, Besse B, Mazieres J, Shapiro GI, Boni V, Waqar SN, Park H, Quinn DI, Martinez A, Stemmer SM, Cortot AB, Barlesi F, Quoix E, Burkard ME, Selcuklu SD, Hunt C, Donoghue MTA, Kris MG, Bebchuk J, Eli LD, McCulloch L, Solit DB, Janne PA. Efficacy of Neratinib-Based Therapy in ERBB2-Mutant Lung Adenocarcinomas: Findings From 2 International Phase 2 Studies. Clin Lung Cancer. 2025 Oct 1:S1525-7304(25)00234-7. doi: 10.1016/j.cllc.2025.09.009. Online ahead of print.
PMID: 41193346DERIVEDFriedman 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.
PMID: 38211393DERIVEDJhaveri 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.
PMID: 37597578DERIVEDHarding 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.
PMID: 36746967DERIVEDShishido 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.
PMID: 35181666DERIVEDOaknin 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.
PMID: 32723675DERIVEDUlaner 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.
PMID: 31548342DERIVEDHanker 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.
PMID: 28274957DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Sr Director, Clinical Operations
- Organization
- Puma Biotechnology, Inc.
Study Officials
- STUDY DIRECTOR
Chief Scientific Officer
Puma Biotechnology, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 26, 2013
First Posted
October 1, 2013
Study Start
September 30, 2013
Primary Completion
January 2, 2023
Study Completion
January 2, 2023
Last Updated
March 12, 2024
Results First Posted
March 12, 2024
Record last verified: 2024-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Clinical study documents and clinical trial data may be requested by qualified researchers and study participants for studies that have been completed for at least 18 months, and for which the indication of the drug has been approved in the US and/or EU, as applicable. Requests will be accepted for up to 24 months after the criteria described in this section are met.
- Access Criteria
- Requestors must provide organizational contact information; a detailed research plan, including outcomes; timeline for completion of the research; qualifications of the research team; funding source; and potential conflicts of interest. Puma will not provide access to patient-level data if there is a reasonable likelihood that individual patients could be identified, or in cases where confidentiality or consent provisions prohibit transfer of data or information to third parties. Additionally, Puma will not disclose information that jeopardizes intellectual property rights or divulges confidential commercial information.
Puma Biotechnology is committed to sharing clinical trial data and information to help physicians and patients make informed treatment decisions, and to help qualified researchers advance scientific knowledge. In accordance with legal and regulatory requirements, Puma publishes study protocol information and clinical study results on clinical trial registries, including ClinicalTrials.gov and EU Clinical Trials Register. Puma also publishes information about clinical studies in peer-reviewed scientific journals and shares data in scientific meetings. Puma commits to safeguarding confidentiality and patient privacy throughout the clinical trial data and information sharing process. Any patient-level data will be anonymized to protect personally identifiable information. Qualified researchers and study participants may submit requests for other study documentation and clinical trial data to clinicaltrials@pumabiotechnology.com for consideration.