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

NCT04905316 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 21-004
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 7

Brief Summary

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).

Conditions

Non-small Cell Lung Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• progression-free survival

  2 years

Secondary Outcomes (1)

• Rate of grade ≥ 2 pneumonitis

  2 years

Study Arms (1)

Canakinumab with Chemoradiation and Durvalumab

EXPERIMENTAL

Treatment 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. Patients that come off treatment for progression, or have progression after completion of all protocol-related therapy, can be followed for survival outcomes by chart review based on standard of care evaluations.

Drug: Canakinumab; Drug: Durvalumab; Radiation: Radiation therapy; Drug: Chemotherapy

Interventions

Canakinumab DRUG

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. Intravenous Canakinumab (ACZ885) should start no sooner than 3 weeks after the last subcutaneous Canakinumab (ACZ885) injection. 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.

Also known as: ACZ885

Canakinumab with Chemoradiation and Durvalumab

Durvalumab DRUG

Patients will be treated with durvalumab either at a dose of 10mg per kilogram of body weight intravenously every 2 weeks or at a 1500 mg fixed dose administered every 4 weeks as consolidation therapy after completion of concurrent chemoradiation therapy, as per standard of care.

Canakinumab with Chemoradiation and Durvalumab

Radiation therapy RADIATION

Radiation therapy will be performed with external beam ionizing radiation as per standard of care in accordance with institutional practice. Intensity-modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT) will be used at the discretion of the treating radiation oncologist. Patients will be simulated in the treatment position with standard immobilization techniques for thoracic radiotherapy. The prescription dose will be 60 Gy (±10%) in 2Gy fractions to fields encompassing gross tumor and lymph nodes, as per institutional guidelines. The dose must satisfy institutional guidelines and minimize risk to adjacent organs at risk.

Canakinumab with Chemoradiation and Durvalumab

Chemotherapy DRUG

Chemotherapy will be as per standard of care in accordance with institutional practice. Patients will be treated with carboplatin or cisplatin with etoposide, paclitaxel, albumin-bound paclitaxel or pemetrexed at the discretion of the treating thoracic medical oncologist. Chemotherapy will be concurrent with radiation therapy as per standard practice, with cycle 1 day 1 of chemotherapy starting on fraction 1 of radiation ± 5 days.

Canakinumab with Chemoradiation and Durvalumab

Eligibility Criteria

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

You may qualify if:

• 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 physician.
• AST (SGOT)/ALT (SGPT) ≤2.5 x institutional upper limit of normal

You may not qualify if:

• 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 criterion:
• 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 pathways.
• Prior treatment with canakinumab

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

canakinumab; durvalumab; Radiotherapy; Drug Therapy

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Narek Shaverdian, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm, prospective, phase I/II study.

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 27, 2021
• Study Start: May 21, 2021
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (7)