Osimertinib and Bevacizumab Versus Osimertinib Alone as Second-line Treatment in Stage IIIb-IVb NSCLC With Confirmed EGFRm and T790M

NCT03133546 | Completed Phase 2 Results DMC

• 4 other identifiers: ETOP 10-162016-002029-12ESR-15-11666MO39447
• Study Type: interventional
• Target: 155
• Locations: 6 countries
• Sites: 25

Brief Summary

BOOSTER is a randomised, controlled, phase II trial comparing osimertinib and bevacizumab versus osimertinib alone as second-line treatment in patients with stage IIIb-IVb non-small cell lung carcinoma (NSCLC) harbouring activating EGFR (exon 19 deletion or L858R) and T790M resistance mutation.

Conditions

Non Small Cell Lung Cancer Metastatic

Keywords

NSCLC; EGFR; TKI; EGFRm; T790M

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the time from the date of randomisation until documented progression (based on RECIST 1.1 criteria) or death, if progression is not documented. Censoring (for patients without progression/death) will occur at the last tumour assessment if patient is lost to follow-up or refuses further documentation of follow-up.

  Evaluated up to approximately 45 months from the randomisation of the first patient.

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  Evaluated up to approximately 45 months from the randomisation of the first patient.

• Disease Control Rate (DCR)

  Evaluated up to approximately 45 months from the randomisation of the first patient.

• Adverse Events

  Evaluated up to approximately 45 months from the randomisation of the first patient.

• Overall Survival (OS)

  Evaluated up to approximately 45 months from the randomisation of the first patient.

Other Outcomes (1)

• T790M Evolution in Tissue and Plasma/Serum Between Baseline and Disease Progression (PD) on Trial Treatment.

  Available for translational research, following completion of the primary trial research objectives.

Study Arms (2)

Osimertinib plus Bevacizumab

EXPERIMENTAL

Patients will receive treatment with osimertinib and bevacizumab until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit.

Drug: Osimertinib; Drug: Bevacizumab

Osimertinib alone

ACTIVE COMPARATOR

Patients will receive treatment with osimertinib until disease progression, lack of tolerability or the patient declines further treatment. Treatment may also continue beyond progression for as long as the patient may still derive benefit.

Drug: Osimertinib

Interventions

Osimertinib DRUG

Osimertinib is administered orally at 80mg once daily. Doses should be taken approximately 24 hours apart at the same time point each day. The appropriate number of osimertinib tablets will be provided to patients to be self-administered at home. AstraZeneca will supply osimertinib as tablets for oral administration. AstraZeneca will supply osimertinib as tablets for oral administration.

Also known as: Tagrisso

Osimertinib alone; Osimertinib plus Bevacizumab

Bevacizumab DRUG

Bevacizumab is administered at 15mg/kg intravenously on day 1 of every 3-week cycle. Bevacizumab for intravenous administration will be supplied by Roche.

Also known as: Avastin

Osimertinib plus Bevacizumab

Eligibility Criteria

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

You may qualify if:

• Patients (male/female) must be \>18 years of age.
• Patients diagnosed with NSCLC, stage IIIb/IIIc (not amenable to radical therapy) or IVa/IVb according to 8th TNM classification, after progression following prior EGFR TKI therapy (erlotinib, gefitinib, dacomitinib or afatinib) as the most recent treatment regimen;
• Pathological diagnosis of predominantly non-squamous NSCLC;
• Maximum one line of previous platinum based chemotherapy;
• Histological or cytological confirmation of EGFRm (exon 19 deletion or exon 21L858R);
• Locally confirmed T790M mutation determined from biopsy (preferred) or on circulating tumour DNA, documented in tissue, plasma or serum after disease progression on the most recent treatment regimen;
• Plasma, serum, and tumour (preferred) tissue or cytology (if biopsy was taken and FFPE tumor material is not yet fully depleted) after disease progression on the most recent EGFR TKI treatment available for central confirmation of T790M;
• Measurable or evaluable disease according to RECIST 1.1;
• Adequate haematological, renal and liver function;
• World Health Organization (WHO) performance status 0-2.

You may not qualify if:

• Patients with mixed NSCLC with predominantly squamous cell cancer, or with any small cell lung cancer (SCLC) component;
• Symptomatic or active central nervous system metastases, as indicated by progressive growth or increasing need of steroids.
• Patients currently receiving medications or herbal supplements known to be potent CYP3A4 inducers;
• Patients with any unresolved toxicities from prior therapy greater than CTCAE V 4.0 grade 1 (exception: alopecia \& grade 2, prior platinuma-therapy related neuropathy)
• Previous treatment with osimertinib and/or bevacizumab;

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• AstraZeneca: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (25)

St. James Hospital

Dublin, Ireland

Location

Mid Western Cancer Centre

Limerick, Ireland

Location

VU University Medical Centre

Amsterdam, Netherlands

Location

National University Hospital

Singapore, Singapore

Location

Tan Tock Seng Hospital

Singapore, Singapore

Location

National Cancer Centre

Goyang, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Teresa Herrara

A Coruña, Spain

Location

Hospital General Alicante

Alicante, Spain

Location

Hospital Sant Pau

Barcelona, Spain

Location

ICO Badalona

Barcelona, Spain

Location

ICO Hospitalet

Barcelona, Spain

Location

OSI Bilbao Basurto

Bilbao, Spain

Location

Fund. Jimenez Diaz

Madrid, Spain

Location

Hospital de la Princesa

Madrid, Spain

Location

Hospital la Paz

Madrid, Spain

Location

Hospital Puerta de Hierro

Madrid, Spain

Location

Hospital Virgen del Rocio

Seville, Spain

Location

Hospital Arnau de Vilanova

Valencia, Spain

Location

Hospital General de Valencia

Valencia, Spain

Location

Geneva University Hospital (HUG)

Geneva, Switzerland

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

Kantonsspital Winterthur

Winterthur, Switzerland

Location

UniversitatSpital Zurich

Zurich, Switzerland

Location

Related Publications (6)

• Bonomi PD. Implications of key trials in advanced nonsmall cell lung cancer. Cancer. 2010 Mar 1;116(5):1155-64. doi: 10.1002/cncr.24815.

  PMID: 20087963 BACKGROUND

• Jackman DM, Miller VA, Cioffredi LA, Yeap BY, Janne PA, Riely GJ, Ruiz MG, Giaccone G, Sequist LV, Johnson BE. Impact of epidermal growth factor receptor and KRAS mutations on clinical outcomes in previously untreated non-small cell lung cancer patients: results of an online tumor registry of clinical trials. Clin Cancer Res. 2009 Aug 15;15(16):5267-73. doi: 10.1158/1078-0432.CCR-09-0888. Epub 2009 Aug 11.

  PMID: 19671843 BACKGROUND

• Oxnard GR, Arcila ME, Sima CS, Riely GJ, Chmielecki J, Kris MG, Pao W, Ladanyi M, Miller VA. Acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant lung cancer: distinct natural history of patients with tumors harboring the T790M mutation. Clin Cancer Res. 2011 Mar 15;17(6):1616-22. doi: 10.1158/1078-0432.CCR-10-2692. Epub 2010 Dec 6.

  PMID: 21135146 BACKGROUND

• Rosell R, Carcereny E, Gervais R, Vergnenegre A, Massuti B, Felip E, Palmero R, Garcia-Gomez R, Pallares C, Sanchez JM, Porta R, Cobo M, Garrido P, Longo F, Moran T, Insa A, De Marinis F, Corre R, Bover I, Illiano A, Dansin E, de Castro J, Milella M, Reguart N, Altavilla G, Jimenez U, Provencio M, Moreno MA, Terrasa J, Munoz-Langa J, Valdivia J, Isla D, Domine M, Molinier O, Mazieres J, Baize N, Garcia-Campelo R, Robinet G, Rodriguez-Abreu D, Lopez-Vivanco G, Gebbia V, Ferrera-Delgado L, Bombaron P, Bernabe R, Bearz A, Artal A, Cortesi E, Rolfo C, Sanchez-Ronco M, Drozdowskyj A, Queralt C, de Aguirre I, Ramirez JL, Sanchez JJ, Molina MA, Taron M, Paz-Ares L; Spanish Lung Cancer Group in collaboration with Groupe Francais de Pneumo-Cancerologie and Associazione Italiana Oncologia Toracica. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2012 Mar;13(3):239-46. doi: 10.1016/S1470-2045(11)70393-X. Epub 2012 Jan 26.

  PMID: 22285168 BACKGROUND

• Finlay MR, Anderton M, Ashton S, Ballard P, Bethel PA, Box MR, Bradbury RH, Brown SJ, Butterworth S, Campbell A, Chorley C, Colclough N, Cross DA, Currie GS, Grist M, Hassall L, Hill GB, James D, James M, Kemmitt P, Klinowska T, Lamont G, Lamont SG, Martin N, McFarland HL, Mellor MJ, Orme JP, Perkins D, Perkins P, Richmond G, Smith P, Ward RA, Waring MJ, Whittaker D, Wells S, Wrigley GL. Discovery of a potent and selective EGFR inhibitor (AZD9291) of both sensitizing and T790M resistance mutations that spares the wild type form of the receptor. J Med Chem. 2014 Oct 23;57(20):8249-67. doi: 10.1021/jm500973a. Epub 2014 Oct 1.

  PMID: 25271963 BACKGROUND

• Camidge DR, Pao W, Sequist LV. Acquired resistance to TKIs in solid tumours: learning from lung cancer. Nat Rev Clin Oncol. 2014 Aug;11(8):473-81. doi: 10.1038/nrclinonc.2014.104. Epub 2014 Jul 1.

  PMID: 24981256 BACKGROUND

MeSH Terms

Interventions

osimertinib; Bevacizumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. Heidi Roschitzki, PhD
• Organization: ETOP IBCSG Partners Foundation

heidi.roschitzki@etop.ibcsg.org

+41 31 511 94 00

Study Officials

• Solange Peters, MD

  Centre Hospitalier Universitaire Vaudois

  STUDY CHAIR

• Rolf Stahel, MD

  University Hospital Zuerich, Zurich, Switzerland

  STUDY CHAIR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 20, 2017
• First Posted: April 28, 2017
• Study Start: May 31, 2017
• Primary Completion: February 22, 2021
• Study Completion: February 29, 2024
• Last Updated: February 6, 2026
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2); ES (13); CH (5); NL (1); KR (2); IE (2)