Neratinib With and Without Temsirolimus for Patients With HER2 Activating Mutations in Non-Small Cell Lung Cancer

NCT01827267 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: PUMA-NER-42012012-004743-68
• Study Type: interventional
• Target: 62
• Locations: 2 countries
• Sites: 21

Brief Summary

This is a Phase 2, therapeutic-exploratory, adaptive design, open-label, multicenter, multinational study evaluating neratinib monotherapy and neratinib plus temsirolimus combination therapy in patients with non-small cell lung cancer (NSCLC) who have documented somatic HER2 mutations.

Conditions

HER2-mutant Non-Small Cell Lung Cancer

Keywords

Lung cancer; Puma; neratinib; HKI-272; PB-272; Nerlynx

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as proportion of subjects who achieved confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A complete or partial response must be confirmed no less than 4-weeks after the criteria for response are initially met.

  From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.

Secondary Outcomes (4)

• Clinical Benefit Rate (CBR)

  From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.

• Duration of Response (DOR)

  From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.

• Progression Free Survival (PFS)

  From randomization to last tumor assessment, assessed up to 116.5 weeks. For the Neratinib arm, only tumor assessments prior to crossover were included.

• Overall Survival (OS)

  From randomization to death or end of long term follow-up, assessed up to 31.8 months.

Study Arms (2)

neratinib monotherapy

EXPERIMENTAL

240 mg once daily with food, continuously in 21 day cycles

Drug: neratinib

neratinib plus temsirolimus

EXPERIMENTAL

240 mg neratinib plus 8 mg temsirolimus IV with optional dose escalation to 15 mg temsirolimus

Drug: neratinib; Drug: temsirolimus

Interventions

neratinib DRUG

Also known as: Nerlynx

neratinib monotherapy; neratinib plus temsirolimus

temsirolimus DRUG

Also known as: Torisel

neratinib plus temsirolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥18 years at the time of signing the informed consent.
• Histologically confirmed diagnosis of NSCLC, advanced (stage IIIB) or metastatic (stage IV).
• Documented somatic ErbB2 (HER2) activating mutation.
• Patients with anaplastic lymphoma kinase (ALK) translocations must have received crizotinib, except for cases of intolerable toxicity to crizotinib.
• At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) status \<2.
• Left ventricular ejection fraction (LVEF) ≥50% measured by multiple -gated acquisition scan (MUGA) or echocardiogram (ECHO).
• Negative β-human chorionic gonadotropin (hCG) pregnancy test for premenopausal women of reproductive capacity (those who are biologically capable of having children) and for women less than 12 months after menopause.
• Men and women of childbearing potential must agree and commit to the use of a highly effective method of contraception, as determined to be acceptable by the Investigator, from the time of informed consent until 3 months after the last dose of the investigational products.
• Provide written, informed consent to participate in the study and follow the study procedures.

You may not qualify if:

• Previous treatment with any investigational agent ≤14 days prior to the initiation of investigational products.
• Previous treatment with any strong inhibitor and/or inducer of CYP3A4 enzyme or sensitive P-glycoprotein (P-gp) substrates ≤30 days prior to the initiation of investigational products.
• Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (New York Heart Association functional classification of ≥2), unstable angina, myocardial infarction within 12 months of enrollment, or ventricular arrhythmia.
• Major surgery \<30 days of starting treatment.
• Chronic steroid use (prednisone \>12.5 mg/day or dexamethasone \>2 mg/day, excluding inhaled steroids).
• Currently breast feeding.
• Symptomatic or unstable brain metastases.
• QTc interval \>0.450 seconds for men and \>0.470 seconds for women, or known history of QTc prolongation or Torsades de Pointes (TdP).
• Significant chronic gastrointestinal disorder with diarrhea as a major symptom (e.g., Crohn's disease, malabsorption, or Grade ≥2 (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events Version 4.0 \[CTCAE v.4.0\] diarrhea of any etiology at baseline).
• Prior exposure to neratinib or mTOR inhibitor.
• Active infection or unexplained fever \>38.5°C (101.3°F).
• Unable or unwilling to swallow tablets.
• Evidence of significant medical illness, abnormal laboratory finding, or psychiatric illness/social situations that would, in the Investigator's judgment, make the patient inappropriate for this study.
• Known hypersensitivity to any component of the investigational products.
• Unstable or uncontrolled diabetes mellitus (glycosylated hemoglobin \[HbA1c\] \>6.5%).

Sponsors & Collaborators

• Puma Biotechnology, Inc.: lead

Study Sites (21)

City of Hope

Duarte, California, 91010, United States

Location

University of California Los Angeles

Santa Monica, California, 94040, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Massachusettes General Hospital

Boston, Massachusetts, 02215, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

CHU de Grenoble Hopital Albert Michallon

Grenoble, 38043, France

Location

CHRU de Lille - Hopital Calmette

Lille, 59037, France

Location

Hopital Nord

Marseille, 13915, France

Location

Hopitaux universitaires de Strasbourg Nouvel Hopital Civil

Strasbourg, 167091, France

Location

CHU de Toulous Hopital Larre

Toulouse, 30030, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Li 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: 41193346 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

neratinib; temsirolimus

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Director, Clinical Operations
• Organization: Puma Biotechnology

clinicaltrials@pumabiotechnology.com

+1 (424) 248-6500

Study Officials

• Clinical Development Senior Vice President

  Puma Biotechnology, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2013
• First Posted: April 9, 2013
• Study Start: July 1, 2013
• Primary Completion: September 20, 2016
• Study Completion: October 6, 2017
• Last Updated: July 3, 2018
• Results First Posted: September 11, 2017

Record last verified: 2018-05

Locations

FR (6); US (15)