Clinical trial NCT01953926: Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Official title: An Open-Label, Phase 2 Basket Study of Neratinib in Patients With Solid Tumors With Somatic Activating HER Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations
Keywords: Neratinib
Nerlynx
Breast
Solid Tumors
Cancer
HER2 mutations
EGFR mutations
Fulvestrant
Trastuzumab
Cervical
Salivary
ERBB2
Exon 18
Metastatic
HR Positive
Lung
Non-Small Cell Lung Cancer (NSCLC)
Lead sponsor: Puma Biotechnology, Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-01
Enrollment: 582
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: 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. The study has a basket design and includes several cohorts, either defined by an actionable somatic mutation or by actionable mutation and tumor histology, including HER2 mutant breast, HER2 mutant cervical, HER2 mutant salivary gland, and EGFR Exon 18 mutant Non-small cell lung cancers.

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.

Eligibility criteria: 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) 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

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

Primary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
timeFrame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
measure: Confirmed Objective Response Rate (ORR) by Investigator Review (Cervical Cancer Cohort)
timeFrame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
measure: Objective Response Rate (ORR) at First Assessment by Investigator Review (All Other Cohorts)
timeFrame: From first treatment date to first Complete or Partial Response, whichever came earlier, assessed up to 8 or 9 weeks
Secondary outcomes:
measure: Confirmed Objective Response Rate (ORR) by Investigator Review (Breast Cancer With Prior CDK46i Cohort)
timeFrame: From enrollment date to first confirmed Complete or Partial Response, whichever came earlier, assessed up to 58 months
measure: Confirmed Objective Response Rate (ORR) by Investigator Review (All Other Cohorts)
timeFrame: From first treatment date to confirmed Complete or Partial Response, assessed up to 58 months.
measure: Duration of Response (DOR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
timeFrame: From first response to first disease progression or death, assessed up to 58 months
measure: Duration of Response (DOR) by Investigator Review (All Cohorts)
timeFrame: From first response to first disease progression or death, assessed up to 58 months
measure: Clinical Benefit Rate (CBR) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
timeFrame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months
measure: Clinical Benefit Rate (CBR) by Investigator Review (All Cohorts)
timeFrame: From enrollment date to first documented response or stable disease ≥16, or ≥24 weeks for breast cancer, assessed up to 58 months
measure: Progression-Free Survival (PFS) by Independent Central Review (Breast Cancer With Prior CDK46i Cohort)
timeFrame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months
measure: Progression-Free Survival (PFS) by Investigator Review (All Cohorts)
timeFrame: From enrollment date until the date of first documented progression, or date of death from any cause, whichever came first, assessed up to 58 months
measure: Number of Participants With Treatment-Emergent Adverse Events
timeFrame: From first dose through 28 days after the last dose, assessed up to 75 months.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente NoCal (STRATA)
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis Park
country: United States
facility: Metro Minnesota Community Oncology Research Consortium
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Pittsburgh
country: United States
facility: UPMC Magee-Woman's Hospital, Women's Cancer Center
state: Pennsylvania
city: Greenville
country: United States
facility: Saint Francis Cancer Center-Bon Secours
state: South Carolina
city: Germantown
country: United States
facility: The West Clinic
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: La Crosse
country: United States
facility: Gundersen Center for Cancer and Blood Disorders
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Leuven
country: Belgium
facility: UZ Leuven
city: Vancouver
country: Canada
facility: British Columbia Cancer Center
state: British Columbia
city: Kopenhagen
country: Denmark
facility: University Hospital, Rigshospitalet
city: Saint-Cloud
country: France
facility: Institut Curie - Hopital Rene Huguenin
state: Ile De France
city: Villejuif
country: France
facility: Institut Gustave Roussy
state: Paris
city: Bordeaux
country: France
facility: Institut Bergonié
city: Lyon
country: France
facility: Centre Leon Berard
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
state: Leinster
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Davidoff Cancer Center, Rabin Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Sourasky Medical Center
city: Cremona
country: Italy
facility: Azienda Socio Sanitaria Territoriale di Cremona
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia (IEO) I.R.C.C.S.
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Gemelli I.R.C.C.S.
city: Torino
country: Italy
facility: AOU Citta della Salute e della Scienza di Torino
city: Seodaemun-Gu
country: Korea, Republic of
facility: Yonsei University Health System, Serverance Hospital
state: Seoul
city: Belgrade
country: Serbia
facility: Institute for Oncology and Radiology of Serbia
city: Barcelona
country: Spain
facility: Hospital Universitario Quiron Dexeus
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Universitari Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico Universitario San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro (START Madrid)
city: Madrid
country: Spain
facility: Hospital Universitario Quiron Madrid
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Puma Biotechnology, Inc.
name: Chief Scientific Officer
role: STUDY_DIRECTOR
References:
citation: 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.
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citation: 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.
citation: 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.
citation: 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.
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