TIGER-3: Open Label, Multicenter Study of Rociletinib (CO-1686) Mono Therapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR NSCLC Who Have Failed at Least One Previous EGFR-Directed TKI and Platinum-doublet Chemotherapy

NCT02322281 | Terminated Phase 3 Results DMC

• 1 other identifier: CO-1686-020 (TIGER-3)
• Study Type: interventional
• Target: 149
• Locations: 10 countries
• Sites: 80

Brief Summary

The purpose of this study is to compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy.

Conditions

Non-small Cell Lung Cancer

Keywords

cancer; metastatic; locally advanced; lung; non-small cell lung cancer; NSCLC; epidermal growth factor receptor; EGFR; T790M; CO-1686; unresectable; recurrent; EGFR-directed therapy; irreversible EGFR inhibitor; TIGER; Rociletinib

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)

  PFS was calculated as 1+ the number of days from the date of randomization to documented radiographic progression as determined by the investigator, or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression.

  Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.

Secondary Outcomes (4)

• Percentage of Participants With Confirmed Response

  Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for best overall confirmed response.

• Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment

  Cycle 1 Day 1 to End of Treatment, up to approximately 35 months

• Overall Survival (OS)

  Cycle 1 Day 1 to date of death, assessed up to 3 years

• Plasma PK for Patients Treated With Rociletinib Based on Sparse Sampling

  Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months

Study Arms (3)

Rociletinib Monotherapy (500 mg BID)

EXPERIMENTAL

Daily oral rociletinib at 500 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.

Drug: Rociletinib

Rociletinib Monotherapy (625 mg BID)

EXPERIMENTAL

Daily oral rociletinib at 625 mg BID with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Treatment with rociletinib is continuous and each cycle will comprise of 21 days.

Drug: Rociletinib

Pemetrexed or gemcitabine or paclitaxel or docetaxel

ACTIVE COMPARATOR

Pemetrexed 500 mg/m2 pemetrexed given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 gemcitabine given intravenously on Day 1 and 8 of each 21-day cycle. Docetaxel 75 mg/m2 docetaxel (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle. or 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Paclitaxel 80 mg/m2 paclitaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle.

Drug: Pemetrexed or gemcitabine or paclitaxel or docetaxel

Interventions

Rociletinib DRUG

Also known as: CO-1686

Rociletinib Monotherapy (500 mg BID); Rociletinib Monotherapy (625 mg BID)

Pemetrexed or gemcitabine or paclitaxel or docetaxel DRUG

Pemetrexed or gemcitabine or paclitaxel or docetaxel

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed metastatic or unresectable locally advanced NSCLC with radiological progression on the most recent therapy received
• Documented evidence of a tumor with 1 or more EGFR activating mutations excluding exon 20 insertion
• Disease progression confirmed by radiological assessment while receiving treatment with single agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib) or EGFR-TKI in combination with other targeted therapy (e.g. bevacizumab, immunotherapy)
• Multiple lines of prior treatment are permitted and there is no specified order of treatment, but in the course of their treatment history, patients must have received and have radiologically documented disease progression following:
• At least 1 line of prior treatment with a single-agent EGFR-TKI (e.g., erlotinib, gefitinib, afatinib, or dacomitinib)
• If EGFR-TKI is a component of the most recent treatment line, the washout period for the EGFR-TKI is a minimum of 3 days before the start of study drug treatment
• AND
• A platinum-containing doublet chemotherapy (either progressed during therapy or completed at least 4 cycles without progression with subsequent progression after a treatment-free interval or after a maintenance treatment).
• If cytotoxic chemotherapy is a component of the most recent treatment line, treatment with chemotherapy should have been completed at least 14 days prior to start of study treatment. When an EGFR-TKI is given in combination with platinum-containing doublet chemotherapy, treatment with the EGFR-TKI may continue until at least 3 days before start of treatment.
• Have undergone a biopsy of either primary or metastatic tumor tissue within 60 days prior to start of treatment and have tissue sent to the central laboratory prior to randomization
• Measureable disease according to RECIST Version 1.1
• Life expectancy of at least 3 months
• ECOG performance status of 0 to 1
• Age ≥ 18 years (in certain territories, the minimum age requirement may be higher e.g., age ≥ 20 years in Japan and Taiwan, age ≥ 21 years in Singapore)
• Patients should have recovered to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 from any significant chemotherapy-related toxicities

You may not qualify if:

• Any of the following criteria will exclude patients from study participation:
• Any other malignancy associated with a high mortality risk within the next 5 years and for which the patients may be (but not necessarily) currently receiving treatment
• Patients with a history of malignancy that has been completely treated, with no evidence of that cancer currently, are permitted to enroll in the trial provided all chemotherapy was completed \> 6 months prior and/or bone marrow transplant \> 2 years prior
• Known pre-existing interstitial lung disease
• Tumor small cell transformation by local assessment, irrespective of presence of T790M+ component
• Patients with leptomeningeal carcinomatosis are excluded. Other central nervous system (CNS) metastases are only permitted if treated, asymptomatic, and stable (not requiring steroids for at least 2 weeks prior to randomization and the patient is neurologically stable i.e. free from new symptoms of brain metastases)
• Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and that treatment cannot be either discontinued or switched to a different medication (known to have no effect on QT) before starting protocol-specified treatment (see http://crediblemeds.org/ for a list of QT-prolonging medications)
• Prior treatment with rociletinib, or other drugs that target T790M+ mutant EGFR with sparing of WT-EGFR including but not limited to osimertinib, HM61713, and TAS-121
• Any contraindications for therapy with pemetrexed, paclitaxel, gemcitabine or docetaxel unless a contraindication with respect to one of these drugs will not affect the use of any of the others as a comparator to rociletinib
• Any of the following cardiac abnormalities or history:
• Clinically significant abnormal 12-lead ECG, QT interval corrected using Fridericia's method (QTCF) \> 450 msec
• Inability to measure QT interval on ECG
• Personal or family history of long QT syndrome
• Implantable pacemaker or implantable cardioverter defibrillator
• Resting bradycardia \< 55 beats/min

Sponsors & Collaborators

• Clovis Oncology, Inc.: lead

Study Sites (80)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

City of Hope Cancer Center

Duarte, California, 91010, United States

Location

Saint Joseph Heritage Healthcare

Fullerton, California, 92835, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093-0698, United States

Location

Cancer Care Associates Medical Group, Inc.

Redondo Beach, California, 90277, United States

Location

Sutter Cancer Center

Sacramento, California, 95816, United States

Location

University of California, San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Central Coast Medical Oncology Corporation

Santa Maria, California, 93454, United States

Location

University of California at Los Angeles

Santa Monica, California, 90404, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

The Oncology Institute of Hope and Innovation

Whittier, California, 90603, United States

Location

Sylvester Comprehensive Cancer Center (UMHC)

Deerfield Beach, Florida, 33442, United States

Location

University of Florida Health Science Center

Gainesville, Florida, 32608, United States

Location

Memorial Healthcare System

Pembroke Pines, Florida, 33028, United States

Location

Northside Hospital

Atlanta, Georgia, 30341, United States

Location

North Shore University Health System

Evanston, Illinois, 60201, United States

Location

Walter Reed National Military Medical Center

Bethesda, Maryland, 20889, United States

Location

Saint Joseph Mercy Hospital

Ann Arbor, Michigan, 48106, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Regional Cancer Care Associates, LLC

East Brunswick, New Jersey, 08816, United States

Location

Regional Cancer Care Associates

Morristown, New Jersey, 07962, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

The Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Providence Health and Services

Portland, Oregon, 97223, United States

Location

Oregon Health & Science University (OHSU) - Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Cancer Institute (UPMC)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Institute

Richmond, Virginia, 23230, United States

Location

Royal North Shore Hospital

Saint Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Hopital Hautepierre (CHU) de Strasbourg

Strasbourg, Alsace, 67091, France

Location

Centre François Baclesse

Caen, Basse-Normandie, 14076, France

Location

Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou

Rennes, Brittany Region, 35033, France

Location

CHRU de Lille - Hôpital Calmette

Lille, Hauts-de-France, 59037, France

Location

CHRU de Limoges - Hôpital Dupuytren

Limoges, Limousin, 87042, France

Location

L'Assistance Publique - Hopitaux de Marseille

Marseille, Provence-Alpes-Côte d'Azur Region, 13009, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Centre Hospitalier Intercommunal Créteil

Créteil, Île-de-France Region, 94010, France

Location

Hôpital Bichat-Claude Bernard

Paris, Île-de-France Region, 75018, France

Location

Asklepios Fachkliniken München-Gauting

Gauting, Baden-Wurttemberg, 82131, Germany

Location

Thoraxklinik Heidelberg gGmbH

Heidelberg, Baden-Wurttemberg, 69126, Germany

Location

LMU - Klinikum der Universität München

München, Bavaria, 80336, Germany

Location

Pius Hospital Oldenburg

Oldenburg, Niedersachen, 26121, Germany

Location

Johannes-Wesling-Klinikum Minden

Minden, North Rhine-Westphalia, 32429, Germany

Location

LungenClinic Großhansdorf GmbH

Großhansdorf, Schleswig-Holstein, 22927, Germany

Location

A.O.U. San Luigi Gonzaga di Orbassano

Orbassano, Torino, 10043, Italy

Location

Azienda Ospedaliero-Universitaria Careggi

Florence, 50139, Italy

Location

IRCCS Azienda Ospedaliera Universitaria San Martino - IST

Genova, 16132, Italy

Location

Ospedale Civile di Livorno

Livorno, 57124, Italy

Location

Istituto Europeo di Oncologia

Milan, 20141, Italy

Location

Azienda Ospedaliera di Perugia

Perugia, 06132, Italy

Location

Academisch Ziekenhuis Maastricht

Maastricht, Limburg, 6229 HX, Netherlands

Location

Antoni van Leeuwenhoek Hospital

Amsterdam, North Holland, 1066 CX, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, 9700 RB, Netherlands

Location

Chungbuk National University Hospital

Cheongju-si, Cheungcheongbuk-do, 361-712, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

The Catholic University of Korea Saint Vincent's Hospital

Suwon, Gyeonggi-do, 442-723, South Korea

Location

Chonnam National University Hwasun Hospital

Hwasun-gun, Jeollanam-do, 519-809, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Universitari Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital de Mataró

Mataró, Barcelona, 08034, Spain

Location

Institut Universitari Dexeus

Barcelona, 08028, Spain

Location

Hospital Universitari Vall D'Hebron

Barcelona, 08035, Spain

Location

Fundacion Jimenez Diaz (Clinica de la Concepcion) (UAM -FJD)

Madrid, 28040, Spain

Location

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

China Medical University Hospital

Taichung, 40447, Taiwan

Location

Taichung Veterans General Hospital

Taichung, 40705, Taiwan

Location

National Cheng-Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

University College London Hospitals

London, England, NW1 2BU, United Kingdom

Location

Guy's and Saint Thomas NHS Foundation Trust

London, England, SE1 9RT, United Kingdom

Location

Royal Marsden NHS Trust

London, England, SW3 6JJ, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, England, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms; Neoplasm Metastasis; Recurrence

Interventions

rociletinib; Pemetrexed; Gemcitabine; Paclitaxel; Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Limitations and Caveats

Due to early study termination, only 149 of 600 planned patients were randomized.

Results Point of Contact

• Title: Vi Nguyen
• Organization: Clovis Oncology

vnguyen@clovisoncology.com

+1 415 915 9982

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 23, 2014
• Study Start: February 1, 2015
• Primary Completion: March 29, 2018
• Study Completion: March 29, 2018
• Last Updated: August 14, 2019
• Results First Posted: July 23, 2019

Record last verified: 2019-07

Locations

ES (7); GB (4); NL (3); DE (6); TW (5); KR (6); FR (9); IT (6); US (31); AU (3)