Clinical Trials /

A Study of Canakinumab With Chemotherapy, Radiation Therapy, and Durvalumab in People With Lung Cancer



The researchers are doing this study to find out whether canakinumab in combination with chemoradiation and durvalumab is an effective and safe treatment for people with locally advanced non-small cell lung cancer (NSCLC).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:



Phase 2

Trial Eligibility



  • Brief Title: A Study of Canakinumab With Chemotherapy, Radiation Therapy, and Durvalumab in People With Lung Cancer
  • Official Title: Phase I/II Study of Canakinumab With Chemoradiation and Durvalumab for Unresected Locally-Advanced Non-Small Cell Lung Cancer (CHORUS)

Clinical Trial IDs

  • ORG STUDY ID: 21-004
  • NCT ID: NCT04905316


  • Non-small Cell Lung Cancer


CanakinumabACZ885Canakinumab with Chemoradiation and Durvalumab
DurvalumabCanakinumab with Chemoradiation and Durvalumab
ChemotherapyCanakinumab with Chemoradiation and Durvalumab


The researchers are doing this study to find out whether canakinumab in combination with chemoradiation and durvalumab is an effective and safe treatment for people with locally advanced non-small cell lung cancer (NSCLC).

Trial Arms

Canakinumab with Chemoradiation and DurvalumabExperimentalTreatment will consist of canakinumab (ACZ885) administered as a subcutaneous injection every 3 weeks for 3 cycles concurrent with standard of care concurrent chemoradiation, followed by canakinumab administered intravenously every 4 weeks for up to 12 total infusions concurrent with standard of care durvalumab. Canakinumab (ACZ885) will be dosed at 200mg via subcutaneous injection every 3 weeks x 3 injections that will start with concurrent chemoradiation, followed by 200mg via intravenous infusion every 4 weeks x 12 infusions that will start with the initiation of durvalumab. Canakinumab (ACZ885) will be concurrent with thoracic chemoradiation and durvalumab therapy for up to 15 cycles, or until disease progression or unacceptable toxicity, whichever occurs first.
  • Canakinumab
  • Durvalumab
  • Chemotherapy

Eligibility Criteria

        Inclusion Criteria:

          -  Capable of giving signed informed consent which includes compliance with the
             requirements and restrictions listed in the informed consent form (ICF) and in this
             protocol. Written informed consent and any locally required authorization obtained
             from the patient/legal representative prior to performing any protocol- related
             procedures, including screening evaluations.

          -  Patient age ≥ 18 at time of consent

          -  Stage IIIA-C NSCLC (as per the American Joint Commission on Cancer (AJCC) 8th edition)

          -  Not a candidate for surgical resection as determined by one or more of the following
             criteria in multidisciplinary evaluations: technically unresectable, medically
             inoperable, patient declines operative approach

          -  Candidate for concurrent chemoradiation therapy as determined by the treating
             radiation and thoracic oncologist

          -  Histologic confirmation of NSCLC with pathological review done at MSK

          -  ECOG Performance Status 0-1

          -  Candidate for definitive thoracic radiation (defined 60Gy ± 10% in 2 Gy fractions)

          -  Body weight > 30 kg

          -  Adequate normal organ and marrow function as defined below:

               -  Hemoglobin ≥9.0 g/dL

               -  Absolute neutrophil count (ANC) 1.5 x (> 1500 per mm3)

               -  Platelet count ≥100 x 10^9/L (>100,000 per mm3)

               -  Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). This will not
                  apply to patients with confirmed Gilbert's syndrome (persistent or recurrent
                  hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis
                  or hepatic pathology), who will be allowed only in consultation with their

               -  AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

               -  Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40
                  mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour
                  urine collection for determination of creatinine clearance

          -  Evidence of post-menopausal status or negative urinary or serum pregnancy test for
             female pre-menopausal patients. Women will be considered post-menopausal if they have
             been amenorrhoeic for 12 months without an alternative medical cause. The following
             age-specific requirements apply:

               -  Women <50 years of age would be considered post-menopausal if they have been
                  amenorrhoeic for 12 months or more following cessation of exogenous hormonal
                  treatments and if they have luteinizing hormone and follicle-stimulating hormone
                  levels in the post-menopausal range for the institution or underwent surgical
                  sterilization (bilateral oophorectomy or hysterectomy).

               -  Women ≥50 years of age would be considered post-menopausal if they have been
                  amenorrhoeic for 12 months or more following cessation of all exogenous hormonal
                  treatments, had radiation-induced menopause with last menses >1 year ago, had
                  chemotherapy-induced menopause with last menses >1 year ago, or underwent
                  surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or

          -  Patient is willing and able to comply with the protocol for the duration of the study
             including undergoing treatment and scheduled visits and examinations including follow

          -  Must have a life expectancy of at least 6 months

        Exclusion Criteria:

          -  Participation in another clinical study with an investigational (non-FDA approved)
             product during the last 4 weeks

          -  Concurrent enrollment in another clinical study for lung cancer, unless it is an
             observational (non-interventional) clinical study or during the follow-up period of an
             interventional study

          -  Previous thoracic radiation precluding definitive RT

          -  Contraindication to Durvalumab

          -  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], systemic lupus erythematosus, Sarcoidosis syndrome,
             or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid
             arthritis, hypophysitis, uveitis, etc.]). The following are exceptions to this

               -  Patients with vitiligo or alopecia

               -  Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on
                  hormone replacement

               -  Any chronic skin condition that does not require systemic therapy

               -  Patients not on biologic therapy without active disease in the last 3 years may
                  be included but only after consultation with the study physician

               -  Patients with celiac disease controlled by diet alone

          -  Prior/Current Therapies:

               -  Treatment with a administered > 4 weeks earlier (intraocular bevacizumab is
                  acceptable).monoclonal antibody within 4 weeks prior to study Day 1 or has not
                  recovered (i.e., ≥ Grade 1 at baseline) from adverse events due to agents

               -  Patients receiving biologic drugs targeting the immune system (e.g. TNF blockers,
                  anakinra, abatacept, tocilizumab) within 4 weeks prior to study Day 1

               -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137,
                  anti-Cytotoxic Tlymphocyte-associated antigen-4 (CTLA-4) antibody, or any other
                  antibody or drug specifically targeting T-cell co-stimulation or checkpoint

               -  Prior treatment with canakinumab

               -  Current or prior use of a systemic immunosuppressive medication within 14 days
                  before the first dose of canakinumab. The following are exceptions to this

                  i. Intranasal, inhaled, topical steroids, or local steroid injections (e.g.,
                  intra articular injection) ii. Systemic corticosteroids at physiologic doses not
                  to exceed 10 mg/day of prednisone or its equivalent for less than 30 days. iii.
                  Steroids as premedication for hypersensitivity reactions (e.g., CT scan
                  premedication) iv. Systemic glucocorticoid replacement for conditions such as
                  adrenal or pituitary insufficiency.

          -  Major surgical procedure (e.g. intra-cranial, intra-thoracic, intra-abdominal, or
             intra-pelvic) within 28 days prior to the first dose of canakinumab

          -  Prior history of malignant disease, other than NSCLC, that has been diagnosed and/or
             required therapy within the past 3 years. Exceptions to this exclusion include:
             completely resected basal cell and squamous cell skin cancers, completely resected
             carcinoma in situ of any type, and definitely treated Stage 0-I breast cancers on
             hormonal maintenance therapy or definitely treated Stage I-IIA prostate cancer.

          -  History of allogenic organ transplantation.

          -  Known severe concurrent illness:

               -  Known psychiatric or substance abuse disorders that would interfere with
                  cooperation with the requirements of the trial.

               -  Active or recurrent hepatic disorders including cirrhosis, hepatitis B and C.
                  Patients with a past or resolved HBV infection (defined as the presence of
                  hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients
                  positive for hepatitis C (HCV) antibody are eligible only if polymerase chain
                  reaction is negative for HCV RNA.

               -  Active tuberculosis infection (clinical evaluation that includes clinical
                  history, physical examination and radiographic findings, and TB testing in line
                  with local practice)

               -  Human Immunodeficiency Virus (positive HIV 1/2 antibodies).

               -  Active infection requiring systemic therapy.

               -  Evidence of interstitial lung disease or active, non-infectious pneumonitis.

               -  Clinically significant (i.e., active) cardiovascular disease: symptomatic
                  cerebral vascular accident/stroke (< 6 months prior to enrollment), myocardial
                  infarction (< 6 months prior to enrollment), unstable angina, congestive heart
                  failure (≥ New York Heart Association Classification Class II), or serious
                  cardiac arrhythmia requiring medication.

          -  Female patients who are pregnant or breastfeeding or male or female patients of
             reproductive potential unless they are willing to employ a highly effective birth
             control from screening to 130 days after the last dose of canakinumab.

             °Highly effective methods of contraception, defined as one that results in a low
             failure rate (i.e., less than 1% per year) when used consistently and correctly Note
             that condom use during intercourse among sexually actives males will be required. Note
             that some contraception methods are not considered highly effective (e.g. female cap,
             diaphragm, or sponge with or without spermicide; non-copper containing intrauterine
             device; progestogen-only oral hormonal contraceptive pills where inhibition of
             ovulation is not the primary mode of action [excluding Cerazette/desogestrel which is
             considered highly effective]; and triphasic combined oral contraceptive pills).

          -  Connective tissue disorders involving the lung(s) and/or esophagus requiring active
             treatment or idiopathic pulmonary fibrosis

          -  Known history of active primary immunodeficiency

          -  Known allergy or hypersensitivity to any of the study drugs or any of the study drug

          -  Receipt of live vaccination within 3 months prior to the first dose of study durg.
             Note that this only applies to live vaccines.
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:progression-free survival
Time Frame:2 years
Safety Issue:

Secondary Outcome Measures

Measure:Rate of grade ≥ 2 pneumonitis
Time Frame:2 years
Safety Issue:
Description:by CTCAE v. 5.0


Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Locally-advanced NSCLC (stage IIIA-C)
  • Canakinumab
  • Durvalumab
  • Chemoradiation
  • 21-004

Last Updated

May 28, 2021