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

A Randomized Trial of Durvalumab and Tremelimumab ± Platinum-Based Chemotherapy in Patients With Metastatic (Stage IV) Squamous or Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer Metastatic
• Intervention / Treatment: Drug: Durvalumab; Drug: Tremelimumab; Drug: Platinum-Based Drug

Detailed Description

Combinations of durvalumab and tremelimumab have also been studied. While the combination has been studied in over 200 people, it is not clear if it can offer better results when it is combined with chemotherapy.

Recently, immunotherapies that target the PD-1/PD-L1 axis have shown promise in treating patients with non-small cell lung cancer.

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria Park, Australia, 3065
    • St. Vincent's Hospital
  • New South Wales
    • Campbelltown, New South Wales, Australia, 2560
      • Campbelltown Hospital
    • Coffs Harbour, New South Wales, Australia, 2450
      • Coffs Habour Health Campus - NCCI
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • Kingswood, New South Wales, Australia, 2751
      • Nepean Hospital
    • Kogarah, New South Wales, Australia, 2217
      • St. George Hospital, Cancer Care Centre
    • Lismore, New South Wales, Australia, 2480
      • The Tweed Hospital
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Cancer Therapy Centre, Liverpool Hospital
    • Randwick, New South Wales, Australia, 2031
      • Prince of Wales Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Chermside, Queensland, Australia, 4032
      • The Prince Charles Hospital
    • South Brisbane, Queensland, Australia, 4101
      • Mater Research Institute South Brisbane
    • Southport, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Toowoomba, Queensland, Australia, 4350
      • Toowoomba Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Royal Hobart Hospital
  • Victoria
    • Ballarat, Victoria, Australia, 3350
      • Ballarat Health Services
    • Richmond, Victoria, Australia, 3121
      • Epworth HealthCare - Richmond
    • Wodonga, Victoria, Australia, 3690
      • Border Medical Oncology
  • Western Australia
    • Subiaco, Western Australia, Australia, 6008
      • Saint John of God Hospital Subiaco
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • BCCA - Vancouver Cancer Centre
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 5N5
      • Horizon Health Network
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital
    • Moncton, New Brunswick, Canada, E1C 8X3
      • The Vitalite Health Network - Dr. Leon Richard
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Regional Health Authority B, Zone 2
  • Ontario
    • Cambridge, Ontario, Canada, N1R 3G2
      • Cambridge Memorial Hospital
    • Greater Sudbury, Ontario, Canada, P3E 5J1
      • Health Sciences North
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Centre at Hamilton Health Sciences
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • Kitchener, Ontario, Canada, N2G 1G3
      • Grand River Regional Cancer Centre
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Stronach Regional Health Centre at Southlake
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Sault Ste. Marie, Ontario, Canada, P6B 0A8
      • Algoma District Cancer Program
    • St. Catharines, Ontario, Canada, L2S 0A9
      • Niagara Health System
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
    • Toronto, Ontario, Canada, M2K 1E1
      • North York General Hospital
    • Toronto, Ontario, Canada, M3M 0B2
      • Humber River Regional Hospital
    • Toronto, Ontario, Canada, M4C 3E7
      • Michael Garron Hospital
    • Windsor, Ontario, Canada, N8W 2X3
      • Windsor Regional Cancer Centre
  • Prince Edward Island
    • Charlottetown, Prince Edward Island, Canada, C1A 8T5
      • PEI Cancer Treatment Centre
  • Quebec
    • Laval, Quebec, Canada, H7M 3L9
      • Hopital de la Cite-de-la-Sante
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM-Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H3T 1E2
      • The Jewish General Hospital
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Quebec-Hopital l'Enfant-Jesus (HEJ)
    • Québec, Quebec, Canada, G1V 4G5
      • University Institute of Cardiology and
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre Hospitalier Universitaire de Sherbrooke
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• Bilirubin ≤ 1.5 x UNL (upper limit of normal)
• AST and ALT ≤ 2.5 x UNL (if liver metastases are present, ≤5 x UNL) Creatinine < 1.25 UNL or Creatinine clearance ≥ 45 mL/min
• Cytotoxic Chemotherapy: Patients may not have received prior cytotoxic chemotherapy for advanced/metastatic disease.
• Adjuvant Chemotherapy: Patients may have had prior adjuvant therapy for completely resected disease, providing it has been completed at least 12 months prior to randomization.
• Patients treated with concurrent chemotherapy/radiation regimens for unresectable locally advanced Stage III disease will be eligible providing it has been completed at least 12 months prior to randomization.
• Other Systemic Therapy: Patients may not have received prior EGFR or alk inhibitors. Patients may not have received prior treatment with immune-based therapy, including durvalumab and tremelimumab vaccines or oncolytic viral therapy. Patients must have recovered from any reversible treatment related toxicities prior to randomization.
• Prior external beam radiation is permitted provided a minimum of 14 days (2 weeks) have elapsed between the last dose of radiation and date of randomization. Concurrent radiotherapy is not permitted.

Patients must have recovered from any acute toxic effects from radiation prior to randomization.

• Patients must have recovered from any acute toxic effects from radiation prior to randomization.
• Surgery: Previous surgery is permitted provided that wound healing has occurred and at least 14 days have elapsed (major surgery) prior to randomization.
• Patient must be able (i.e. sufficiently fluent) and willing to complete the quality of life and health economics questionnaires.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Patients must be accessible for treatment and follow-up. All randomized patients must be followed and treated at participating centres.
• In accordance with CCTG policy, protocol treatment is to begin within 2 working days of patient randomization.
• Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception while on study and for 6 months after the last dose of durvalumab and tremelimumab or for 3 months after the last dose of durvalumab alone

Exclusion Criteria:

• 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);
  • History of significant neurologic or psychiatric disorder which would impair the ability to obtain consent or limit compliance with study requirements;
  • Active infection requiring systemic therapy; (including any patient known to have active hepatitis B, hepatitis C or human immunodeficiency virus (HIV) or tuberculosis);
  • Active peptic ulcer disease or gastritis;
  • Known pneumonitis or pulmonary fibrosis with clinically significant impairment of pulmonary function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Durvalumab and Tremelimumab; Durvalumab q4 weeks until PD + Tremelimumab q 4 wk x 4 doses	Drug: Durvalumab; MEDI4736; Drug: Tremelimumab; Tremelimumab
Active Comparator: Platinum based chemotherapy + Durvalumab + Tremelimumab; 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; MEDI4736; Drug: Tremelimumab; Tremelimumab; Drug: Platinum-Based Drug; Pemetrexed, cisplatin, carboplatin or gemcitibine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	time from randomization to the date of death	33 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Using RECIST 1.1	time from randomization to the date of the first documented disease progression. Progression was defined as: at least a 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) AND an absolute increase of ≥5 mm, or appearance of new lesions.	33 months
Objective Response Rate Using RECIST 1.1 and iRECIST	proportion of patients with a documented complete response, partial response (CR + PR) based on iRECIST criteria. The primary estimate of ORR will be based on all patients randomized, and compared using Cochran- Mantel-Haeszel test stratified by stratification factors at randomization between the study new treatment and the standard control arms.	33 months

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: National Health and Medical Research Council, Australia; AstraZeneca; Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Investigators: Study Chair: Natasha Leighl, Princess Margaret Hospital, Toronto, ON Canada

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): February 24, 2020
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: February 15, 2017
• First Submitted That Met QC Criteria: February 15, 2017
• First Posted (Actual): February 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; durvalumab; tremelimumab
• Other Study ID Numbers: BR34

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No