Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic Squamous or Non-Squamous NSCLC

NCT03057106 | Active Not Recruiting Phase 2 Results DMC

• 1 other identifier: BR34
• Study Type: interventional
• Target: 301
• Locations: 2 countries
• Sites: 49

Brief Summary

Durvalumab is a new type of drug for many kinds of cancer. It is considered "immunotherapy" and not "chemotherapy". Laboratory tests show that it works by allowing the immune system to detect cancer and reactivate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in more than 5000 people and seems promising. Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. Tremelimumab may also help slow the growth of the cancer cells or may cause cancer cells to die. It has been shown to shrink tumours in animals and has been studied in over 1200 people and seems promising.

Conditions

Lung Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  time from randomization to the date of death

  33 months

Secondary Outcomes (2)

• Progression-free Survival Using RECIST 1.1

  33 months

• Objective Response Rate Using RECIST 1.1 and iRECIST

  33 months

Study Arms (2)

Durvalumab and Tremelimumab

ACTIVE COMPARATOR

Durvalumab q4 weeks until PD + Tremelimumab q 4 wk x 4 doses

Drug: Durvalumab; Drug: Tremelimumab

Platinum based chemotherapy + Durvalumab + Tremelimumab

ACTIVE COMPARATOR

4 cycles platinum plus gem or pem + Durva + Treme (q 3 wk x 4 cycles) Followed by: Squamous Cell: Maintenance Durva q 4 wk until PD Non-Squamous Cell: Pemetrexed + Durva q 4 wk until PD

Drug: Durvalumab; Drug: Tremelimumab; Drug: Platinum-Based Drug

Interventions

Durvalumab DRUG

MEDI4736

Durvalumab and Tremelimumab; Platinum based chemotherapy + Durvalumab + Tremelimumab

Tremelimumab DRUG

Tremelimumab

Durvalumab and Tremelimumab; Platinum based chemotherapy + Durvalumab + Tremelimumab

Platinum-Based Drug DRUG

Pemetrexed, cisplatin, carboplatin or gemcitibine

Platinum based chemotherapy + Durvalumab + Tremelimumab

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically and/or cytologically confirmed diagnosis of squamous or non-squamous, non-small cell carcinoma of the lung. Patients with poorly differentiated tumours will only be eligible if NSCLC is confirmed by immunohistochemistry markers (TTF1/P63 or P40/CK5). Patients with known sensitizing EGFR mutations or known ALK-fusion are not eligible.
• Patients must have stage IV disease according to the 8th TNM version staging.
• Patients must have an adequate histopathology specimen and must consent to release this specimen for protocol required testing. This is a mandatory component of the study.
• Patient must consent to provision of samples of blood in order that the specific correlative marker assays proscribed may be conducted.
• All patients must have measurable disease as defined by RECIST 1.1 All radiology studies must be performed within 28 days prior to randomization (within 35 days if negative).
• The criteria for defining measurable disease are as follows:
• CT scan (with slice thickness of 5 mm) ≥ 10 mm --\> longest diameter
• Physical exam (using calipers) ≥ 10 mm
• Lymph nodes by CT scan ≥ 15 mm --\> measured in short axis
• Measurable lesions must be outside a previous radiotherapy field if they are the sole site of disease, unless disease progression has been documented.
• Patients must be 18 years of age or older.
• ECOG performance status of 0 or 1.
• Absolute neutrophils ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin ≥ 90 g/L

You may not qualify if:

• Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other solid tumours curatively treated with no evidence of disease for ≥ 3 years. Patients with a history of other malignancies detected at an early stage and whom the investigator believes have been curatively treated and are at low risk of recurrence MAY be eligible. Contact CCTG to discuss eligibility prior to enrolling.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
• Patients with alopecia.
• Patients with Grave's disease, vitiligo or psoriasis not requiring systemic treatment (within the last 2 years).
• Patients with hypothyroidism (e.g. following Hashimoto syndrome) stable on hormone replacement.
• History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of randomization\* or a prior history of severe (grade 3 or 4) immune mediated toxicity from other immune therapy or grade ≥ 3 infusion reaction.
• Live attenuated vaccination administered within 30 days prior to randomization
• History of hypersensitivity to durvalumab or tremelimumab or any excipient. Patients who have received other treatment or other antibodies must not have had intolerable toxicity or required steroids to manage toxicity.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msec in screening ECG measured using standard institutional method or history of familial long QT syndrome.
• Patients who have untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if now controlled, should have a LVEF ≥ 45%. (Note: patients with uncomplicated controlled hypertension do not require LVEF measurement in the absence of other significant cardiac history)
• Concurrent treatment with other investigational drugs or anti-cancer therapy
• Patients with untreated brain or meningeal metastases are not eligible. Patients with treated CNS disease who have radiologic AND clinical evidence of stable brain metastases, with no evidence of cavitation or hemorrhage in the brain lesion, are eligible providing that they are asymptomatic and do not require corticosteroids (must have discontinued steroids at least 1 week prior to randomization).
• Pregnant or Lactating Women: Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to randomization. If urine test is positive, pregnancy testing may then include an ultrasound to rule-out pregnancy if a false-positive is suspected. For example, when beta-human chorionic gonadotropin is high and partner is vasectomized, it may be associated with tumour production of hCG, as seen with some cancers. Patient will be considered eligible if an ultrasound is negative for pregnancy. Men and women of child-bearing potential must agree to use adequate contraception.
• Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (including corticosteroid administration), or would put the patient at risk. This includes but is not limited to:
• Contraindications to the use of pemetrexed, gemcitabine, cisplatin and/or carboplatin (consult product monograph);

Sponsors & Collaborators

• Canadian Cancer Trials Group: lead
• AstraZeneca: collaborator
• Fondazione IRCCS Istituto Nazionale dei Tumori, Milano: collaborator
• National Health and Medical Research Council, Australia: collaborator

Study Sites (49)

Campbelltown Hospital

Campbelltown, New South Wales, 2560, Australia

Location

Coffs Habour Health Campus - NCCI

Coffs Harbour, New South Wales, 2450, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2139, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2751, Australia

Location

St. George Hospital, Cancer Care Centre

Kogarah, New South Wales, 2217, Australia

Location

The Tweed Hospital

Lismore, New South Wales, 2480, Australia

Location

Liverpool Cancer Therapy Centre, Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

Location

Prince of Wales Hospital

Randwick, New South Wales, 2031, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Mater Research Institute South Brisbane

South Brisbane, Queensland, 4101, Australia

Location

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

Location

Toowoomba Hospital

Toowoomba, Queensland, 4350, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Ballarat Health Services

Ballarat, Victoria, 3350, Australia

Location

Epworth HealthCare - Richmond

Richmond, Victoria, 3121, Australia

Location

Border Medical Oncology

Wodonga, Victoria, 3690, Australia

Location

Saint John of God Hospital Subiaco

Subiaco, Western Australia, 6008, Australia

Location

St. Vincent's Hospital

Victoria Park, 3065, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

BCCA - Fraser Valley Cancer Centre

Surrey, British Columbia, V3V 1Z2, Canada

Location

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Horizon Health Network

Fredericton, New Brunswick, E3B 5N5, Canada

Location

The Moncton Hospital

Moncton, New Brunswick, E1C 6Z8, Canada

Location

The Vitalite Health Network - Dr. Leon Richard

Moncton, New Brunswick, E1C 8X3, Canada

Location

Regional Health Authority B, Zone 2

Saint John, New Brunswick, E2L 4L2, Canada

Location

Cambridge Memorial Hospital

Cambridge, Ontario, N1R 3G2, Canada

Location

Health Sciences North

Greater Sudbury, Ontario, P3E 5J1, Canada

Location

Juravinski Cancer Centre at Hamilton Health Sciences

Hamilton, Ontario, L8V 5C2, Canada

Location

Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Grand River Regional Cancer Centre

Kitchener, Ontario, N2G 1G3, Canada

Location

Stronach Regional Health Centre at Southlake

Newmarket, Ontario, L3Y 2P9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1H 8L6, Canada

Location

Algoma District Cancer Program

Sault Ste. Marie, Ontario, P6B 0A8, Canada

Location

Niagara Health System

St. Catharines, Ontario, L2S 0A9, Canada

Location

North York General Hospital

Toronto, Ontario, M2K 1E1, Canada

Location

Humber River Regional Hospital

Toronto, Ontario, M3M 0B2, Canada

Location

Michael Garron Hospital

Toronto, Ontario, M4C 3E7, Canada

Location

University Health Network

Toronto, Ontario, M5G 2M9, Canada

Location

Windsor Regional Cancer Centre

Windsor, Ontario, N8W 2X3, Canada

Location

PEI Cancer Treatment Centre

Charlottetown, Prince Edward Island, C1A 8T5, Canada

Location

Hopital de la Cite-de-la-Sante

Laval, Quebec, H7M 3L9, Canada

Location

CHUM-Centre Hospitalier de l'Universite de Montreal

Montreal, Quebec, H2X 3E4, Canada

Location

The Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)

Québec, Quebec, G1J 1Z4, Canada

Location

University Institute of Cardiology and

Québec, Quebec, G1V 4G5, Canada

Location

Centre hospitalier universitaire de Sherbrooke

Sherbrooke, Quebec, J1H 5N4, Canada

Location

Allan Blair Cancer Centre

Regina, Saskatchewan, S4T 7T1, Canada

Location

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, S7N 4H4, Canada

Location

Related Publications (1)

• Leighl NB, Laurie SA, Goss GD, Hughes BGM, Stockler M, Tsao MS, Hwang DM, Joubert P, Kulkarni S, Blais N, Joy AA, Mates M, Rana P, Yadav SK, Underhill C, Lee C, Bradbury PA, Hiltz A, Dancey J, Ding K, Vera-Badillo F; Canadian Cancer Trials Group Lung Disease Site and the Australasian Lung Cancer Trials Group. CCTG BR34: A Randomized Phase 2 Trial of Durvalumab and Tremelimumab With or Without Platinum-Based Chemotherapy in Patients With Metastatic NSCLC. J Thorac Oncol. 2022 Mar;17(3):434-445. doi: 10.1016/j.jtho.2021.10.023. Epub 2021 Nov 17.

  PMID: 34800700 RESULT

MeSH Terms

Interventions

durvalumab; tremelimumab

Limitations and Caveats

The small sample size may prevent the study to find identify the biomarker defined subgroup that may be benefit from the study treatment.

Results Point of Contact

• Title: Dr. Keyue Ding
• Organization: Canadian Cancer Trials Group

kding@ctg.queensu.ca

1-613-533-6430

Study Officials

• Natasha Leighl

  Princess Margaret Hospital, Toronto, ON Canada

  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: February 15, 2017
• First Posted: February 17, 2017
• Study Start: March 28, 2017
• Primary Completion: February 24, 2020
• Study Completion (Estimated): June 30, 2026
• Last Updated: March 3, 2026
• Results First Posted: February 9, 2022

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (30); AU (19)