Study of Erlotinib With or Without Investigational Drug (U3-1287) in Subjects With Advanced Non-small Cell Lung Cancer

NCT01211483 | Completed Phase 1 Results

• 1 other identifier: U31287-A-U201
• Study Type: interventional
• Target: 222
• Locations: 13 countries
• Sites: 52

Brief Summary

This is a Phase 1b/2 study. In Phase 1b, subjects will know the treatment they are receiving. Subjects will receive Erlotinib + U3-1287. The Phase 1b portion will determine if adding U3-1287 to Erlotinib will be safe in subjects with advanced non-small cell lung cancer who fail prior treatment. In the Phase 2 portion, subjects will be blinded to the treatments they are receiving. Subjects will receive either Erlotinib alone or Erlotinib + U3-1287. The Phase 2 portion will determine if adding U3-1287 to Erlotinib will be safe and improve survival in subjects with advanced non-small cell lung cancer who failed the first treatment.

Conditions

NSCLC (Advanced Non-small Cell Lung Cancer)

Keywords

Lung cancer

Outcome Measures

Primary Outcomes (3)

• Progression-Free Survival Following U3-1287 (AMG 888) in Combination With Erlotinib

  Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] Version 1.1).

  Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

• Progression-Free Survival in Participants With High Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib

  Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] Version 1.1). Heregulin (HRG) high is defined as delta cycle threshold value \< 3.9.

  Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

• Progression-Free Survival in Participants With Low Heregulin-Expressing Tumors Following U3-1287 (AMG 888) in Combination With Erlotinib

  Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of first objective documentation of radiographic disease progression or death due to any cause (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] Version 1.1). Heregulin (HRG) low is defined as a delta cycle threshold value ≥ 3.9.

  Time from the randomization date up to the date of first objective documentation of disease progression or death due to any cause (whichever comes first), up to 3 years 2 months

Secondary Outcomes (10)

• Overall Survival Following U3-1287 (AMG 888) in Combination With Erlotinib

  Time from the randomization date up to the date of death due to any cause, up to 3 years 2 months

• Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib

  Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

• Time to Objective Response Following U3-1287 (AMG 888) in Combination With Erlotinib

  Time from date of randomization up to date of first documentation of objective response of either CR or PR (whichever comes first), up to 3 years 2 months

• Duration of Stable Disease Following U3-1287 (AMG 888) in Combination With Erlotinib

  For participants whose best response is SD as the time from date of first documentation of stable disease up to the date of first documentation of progressive disease, up to 3 years 2 months

• Time to Disease Progression Following U3-1287 (AMG 888) in Combination With Erlotinib

  Time from date of randomization up to the date of first objective documentation of disease progression, up to 3 years 2 months

Study Arms (3)

Part A: U3-1287 (high dose) + Erlotinib

EXPERIMENTAL

U3-1287 (high dose) intravenously (IV) every three weeks (Q3W) + Erlotinib 150 mg/day orally (PO) until cancer gets worse, side effects become unacceptable or participant withdraws consent

Drug: U3-1287; Drug: Erlotinib

Part B: U3-1287 (low dose) + Erlotinib

EXPERIMENTAL

U3-1287 (low dose) IV Q3W + Erlotinib 150 mg/day PO until cancer gets worse, side effects become unacceptable or participant withdraws consent

Drug: U3-1287; Drug: Erlotinib

Part B: Placebo + Erlotinib

PLACEBO COMPARATOR

Placebo matching U3-1287 IV Q3W + Erlotinib150 mg/day PO until cancer gets worse, side effects become unacceptable or participant withdraws consent

Drug: Erlotinib; Drug: Placebo

Interventions

U3-1287 DRUG

Liquid 70 mg/mL for IV infusion at high dose or low dose

Also known as: Patritumab

Part A: U3-1287 (high dose) + Erlotinib; Part B: U3-1287 (low dose) + Erlotinib

Erlotinib DRUG

Tablet 150 mg for oral administration

Part A: U3-1287 (high dose) + Erlotinib; Part B: Placebo + Erlotinib; Part B: U3-1287 (low dose) + Erlotinib

Placebo DRUG

Placebo liquid matching U3-1287 for IV infusion

Part B: Placebo + Erlotinib

Eligibility Criteria

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

You may qualify if:

• ≥ 18 years of age.
• Histologically or cytologically confirmed stage IIIB not amenable to surgery or curative intent or stage IV NSCLC.
• Disease progression or recurrence following treatment after last chemotherapy or chemoradiation regimen (completed within the previous 12 months) documented by radiographic assessment.
• Measurable disease by Response Evaluation Criteria for Solid Tumors v1.1 (RECIST v1.1).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow, renal, and hepatic function.
• Prothrombin time and partial thromboplastin time ≤1.5 x upper limit of normal (ULN).
• Availability of recent (before treatment start) or archival tumor specimens (Phase 2 participants only).
• For female participants, must be postmenopausal, surgically sterile, or must use maximally effective birth control during the period of therapy, and must be willing to use effective contraception up to 6 months after the last dose of study drug and had a negative urine or serum pregnancy test before entry into the study if female participants were of childbearing potential.
• For male participants, must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 6 months following the last investigational drug dose
• Written informed consent.

You may not qualify if:

• Left ventricular ejection fraction (LVEF) \< 45%.
• Prior epidermal growth factor receptor (EGFR)-targeted regimen, anti-HER2, anti-HER3, or anti-HER4 therapy.
• More than 2 prior chemotherapy regimens for NSCLC (Phase 2 participants only).
• History of other malignancies, except adequately treated nonmelanoma skin cancer, curatively treated in-situ disease, or other solid tumors curatively treated with no evidence of disease for ≥ 5 years.
• History of corneal disease.
• History of interstitial lung disease.
• Clinically active brain metastases, defined as untreated symptomatic, or requiring therapy with steroids or anticonvulsants to control associated symptoms. Participants with treated brain metastases that were no longer symptomatic and required no treatment with steroids could be included in the study if they had recovered from the acute toxic effect of radiotherapy.
• Uncontrolled hypertension (diastolic \> 100 mmHg or systolic \> 140 mmHg).
• Clinically significant electrocardiogram changes that obscured the ability to assess the respiratory rate, pulse rate, QT, QTc, and QRS intervals.
• Ascites or pleural effusion requiring chronic medical intervention.
• Myocardial infarction within 1 year before enrollment, symptomatic congestive heart failure (New York Heart Association \> Class II), unstable angina, or unstable cardiac arrhythmia requiring medication.
• Treatment with anticancer therapy, antibody based therapy, retinoid therapy, or hormonal therapy within 4 weeks before study treatment or treatment with nitrosoureas or mitomycin C within 6 weeks before study drug treatment or treatment with small molecule tyrosine kinase inhibitors (TKIs) within 2 weeks before study drug treatment. Prior and concurrent use of hormone replacement therapy was permitted.
• Therapeutic radiation or major surgery within 4 weeks before study treatment or palliative radiation therapy within 2 weeks before study drug treatment.
• Participated in clinical drug trials within 4 weeks (2 weeks for small molecule TKIs) before study drug treatment. Current participation in other investigational procedures.
• Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (52)

Unknown Facility

Glendale, Arizona, United States

Location

TRM - Oncology Research Associates, PLLC, d/b/a Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

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Anaheim, California, United States

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Encinitas, California, United States

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La Verne, California, United States

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Los Angeles, California, United States

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Orlando, Florida, United States

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Atlanta, Georgia, United States

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Joliet, Illinois, United States

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Evansville, Indiana, United States

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Baton Rouge, Louisiana, United States

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Detroit, Michigan, United States

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The Bronx, New York, United States

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York, Pennsylvania, United States

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Graz, Austria

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Innsbruck, Austria

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Ghent, Belgium

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Liège, Belgium

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Plovdiv, Bulgaria

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Sofia, Bulgaria

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Essen, Germany

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Frankfurt am Main, Germany

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Freiburg im Breisgau, Germany

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Gauting, Germany

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Halle, Germany

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Hamburg, Germany

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Herne, Germany

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Löwenstein, Germany

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Mainz, Germany

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Tübingen, Germany

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Budapest, Hungary

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Pécs, Hungary

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Petah Tikva, Israel

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Tel Aviv, Israel

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Tel Litwinsky, Israel

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Lido di Camaiore, Italy

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Piacenza, Italy

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Pisa, Italy

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Reggio Emilia, Italy

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Kaunas, Lithuania

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Vilnius, Lithuania

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Suceava, Romania

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Târgu Mureş, Romania

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Golnik, Slovenia

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Dnipropetrovsk, Ukraine

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Donetsk, Ukraine

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Ivano-Frankivsk, Ukraine

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Kharkiv, Ukraine

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Sumy, Ukraine

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Uzhhorod, Ukraine

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London, United Kingdom

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Metropolitan Borough of Wirral, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

patritumab; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sankyo

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2010
• First Posted: September 29, 2010
• Study Start: September 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: November 23, 2013
• Last Updated: June 16, 2021
• Results First Posted: June 16, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

GB (2); BE (2); BU (2); IT (4); AU (2); HU (2); US (14); LI (2); SL (1); UA (6); IL (3); RO (2); DE (10)