Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

Participants received 200 mg of canakinumab in combination with 200 mg of pembrolizumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery

Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery

200 mg of canakinumab administered via subcutaneous injections once every 3 weeks for a maximum duration of 6 weeks

Canakinumab

200 mg of pembrolizumab administered via infusion once every 3 weeks for a maximum duration of 6 weeks

Novartis Pharmaceuticals

The purpose of this study was to evaluate the major pathological response (MPR) rate of canakinumab given as a neoadjuvant treatment, either as single agent or in combination with pembrolizumab, in addition to evaluate the MPR of pembrolizumab as a single agent and the dynamic of the tumor microenvironment changes on treatment.

This was a randomized, phase II, open-label study evaluating canakinumab, an anti-IL-1β monoclonal antibody, or pembrolizumab, a monoclonal antibody designed to block the PD-1 receptor, as monotherapy or in combination as neoadjuvant therapy. The study population included adult subjects with resectable non-small cell lung cancer (NSCLC) planned for surgery in approximately 4-6 weeks. Subjects were treated for a maximum duration of 6 weeks (2 cycles) until surgery, progression, unacceptable toxicity or discontinuation from the study treatment for any other reason.

Subjects were randomized in a 2:2:1 ratio to one of the 3 treatment arms (canakinumab alone or canakinumab in combination with pembrolizumab or pembrolizumab alone). Surgery was performed between 4 to 6 weeks after the first dose of study treatment.

All randomized subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

This Study Will Evaluate the Effect of Canakinumab or Pembrolizumab Given as Monotherapy or in Combination as Neo-adjuvant Treatment for Subjects With Early Stages NSCLC.

A Randomized, Open-label, Phase II Study of Canakinumab or Pembrolizumab as Monotherapy or in Combination as Neoadjuvant Therapy in Subjects With Resectable Non-small Cell Lung Cancer (CANOPY-N)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.

MPR was assessed at the time of surgery in all subjects randomized to canakinumab monotherapy and in combination with pembrolizumab based on central review.

Canakinumab ADA prevalence at baseline was calculated as the percentage of participants who had a canakinumab ADA positive result at baseline

Canakinumab ADA incidence on treatment was calculated as the percentage of participants who were canakinumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and canakinumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

Pembrolizumab ADA prevalence at baseline was calculated as the percentage of participants who had a pembrolizumab ADA positive result at baseline

Pembrolizumab ADA incidence on treatment was calculated as the percentage of participants who were pembrolizumab treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and pembrolizumab treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)

ORR is defined as the percentage of subjects with confirmed best overall response of complete response (CR) or partial response (PR), as per local investigator's assessment by RECIST 1.1.

CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters

Canakinumab serum concentrations were determined at the specified time points.

Pembrolizumab serum concentrations were determined at the specified time points.

Surgical feasibility rate was defined as the percentage of subjects who underwent surgery following study treatment.

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.

MPR was assessed at the time of surgery in all subjects randomized to pembrolizumab monotherapy arm based on central review.

MPR was defined as the percentage of participants with ≤10% residual viable tumor cells on surgical samples. MPR was assessed at the time of surgery based on central review. The difference in MPR rate between the canakinumab plus pembrolizumab arm and the pembrolizumab arm based on central review along with the Chang and Zhang confidence interval was assessed.

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.

MPR was assessed at the time of surgery in all subjects based on local review.

MPR was defined as the percentage of participants with major pathological response (defined as ≤10% residual viable tumor cells on surgical samples). Any participant who had \>10% residual viable cancer cells, or started new antineoplastic therapy prior to surgery, or did not have the surgery performed, or had the surgery performed but with unevaluable MPR result, was considered as a non-responder.

MPR rate was analyzed by the biomarker subgroups at baseline. Biomarkers included PD-L1, CD8, hs-CRP and hs-IL-6.

Any sign or symptom that occurs during the study treatment plus the 130 days post treatment

Canakinumab Monotherapy

Canakinumab + Pembrolizumab

Pembrolizumab Monotherapy

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Study director

All subjects who were randomized to canakinumab monotherapy or canakinumab in combination with pembrolizumab

Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Canakinumab Monotherapy and in Combination With Pembrolizumab Based on Central Review

All subjects randomized to canakinumab monotherapy or canakinumab in combination with pembrolizumab who received at least one dose of canakinumab.

Canakinumab Antidrug Antibodies (ADA) Prevalence

Canakinumab ADA Incidence

All subjects randomized to canakinumab in combination with pembrolizumab or pembrolizumab monotherapy who received at least one dose of pembrolizumab.

Pembrolizumab ADA Prevalence

Pembrolizumab ADA Incidence

FAS including all subjects to whom study treatment was assigned by randomization.

Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1

Cycle 1

Cycle 2

All participants who received at least one dose of canakinumab with at least one evaluable pharmacokinetic (PK) sample. Number analyzed corresponds to the number of participants with an evaluable PK sample at the specified time point

Serum Canakinumab Concentration

Cycle 1 predose

Cyle 1 0.5 hours post dose

Cycle 2 predose

All participants who received at least one dose of pembrolizumab with at least one evaluable PK sample. Number analyzed corresponds to the number of participants with an evaluable PK sample at the specified time point

Serum Pembrolizumab Concentration

Surgical Feasibility Rate

All subjects who were randomized to pembrolizumab monotherapy arm

Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review

All subjects who were randomized to canakinumab in combination with pembrolizumab or pembrolizumab monotherapy arms

Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review

Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review

PD-L1: <1%

PD-L1: 1-49%

PD-L1: >=50%

hs-CRP: <2mg/L

hs-CRP: >=2mg/L

hs-IL-6: <Q1 (2.52 mg/L)

hs-IL-6: >=Q1 (2.52 pg/mL) to <Q2 (5.36 pg/mL)

hs-IL-6: >=Q2 (5.36 pg/mL) to <Q3 (12.03 pg/mL)

hs-IL-6: >=Q3 (12.03 pg/mL)

CD8: <3%

CD8: >=3%

All subjects to whom study treatment was assigned by randomization. Number analyzed is the number of participants with data available for analysis for each category

Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers

Treatment Period

Safety Follow-up Period

Durvalumab

Participants will be diagnosed with Stage I-IIIA NSCLC and will be ineligible for surgery and will have any level of PD-L1

Patients will receive durvalumab 1500mg durvalumab via IV infusion over 1 hour, once every 4 weeks (Q4W) for up to a maximum of 6 months (up to 6 doses/cycles) unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met.

Radiation therapy will be performed with external beam ionizing radiation in accordance with institutional standard practice. 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT) or volumetric arc therapy (VMAT) will be used at the discretion of the treating radiation oncologist.

Stereotactic Body Radiation Therapy

Charles Simone, MD

Maria Thor, PhD, MS

Helaine Bertsch, MD

Rupesh Kotecha, MD

The purpose of this study is to find out whether treatment with the study drug durvalumab combined with a type of radiation therapy called stereotactic body radiation (SBRT) is a more effective treatment for early-stage non-small cell lung cancer (NSCLC) than SBRT alone.

Treating Early-stage Non-Small Cell Lung Cancer With Durvalumab and Radiation Therapy

Stereotactic Body Radiation Therapy With Consolidation Durvalumab in High-Risk Early-Stage Non-Small Cell Lung Cancer - A Phase II Single-Arm Trial

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

The primary objective of the study is to evaluate 2- year progression-free survival (PFS) per RECIST 1.1 with durvalumab combined with stereotactic body radiation therapy (SBRT) compared to historical controls with SBRT alone.

AstraZeneca

Memorial Sloan Kettering Cancer Center

This cohort will follow a strict schedule of Low Dose Computed Tomography Imaging scans and clinical visits 3, 6, and 12 months after surgery. At each encounter, a history, physical examination, and review of the LDCT results will be performed. Patients with normal clinical and imaging findings will proceed to the next scheduled clinical encounter. Patients with abnormal findings will be managed according to predetermined algorithms.

The control group will be a retrospective cohort taken from 1-year before the implementation of the LDCT surveillance program. The post-operative follow-up of these participants was not standardized, but rather left up to the discretion of the individual surgeons, and involved chest radiograph imaging as opposed to Low Dose Computed Tomography.

Low Dose Computed Tomography Imaging

Chest Radiograph Imaging

Wael C Hanna, MDCM MBA FRCSC FCCP

After curative lung cancer surgery, there is a risk of recurrence of the primary cancer, or development of a new cancer. Historically, patients who have undergone curative lung cancer surgery have been monitored with chest radiographs (CXR). Unfortunately, 70% of such patients still die of lung cancer. As a result, there has been interest in other methods of surveillance in order to detect recurring or new cancers earlier and have more success in treating them. One such technique is Low Dose Computed Tomography (LDCT), which is currently the standard of care and surveillance at this institution. This pilot study aims to determine whether regimented, intensive, short interval LDCT surveillance leads to higher rates of detection and treatment of recurring lung cancers. The study group will be followed up according to a regimented surveillance program using LDCT. The study group will be compared to a group of historical controls whose follow up after surgery was not standardized, but rather left up to the discretion of the individual surgeon. If the results of this study show improvements in detection and treatment of recurrent cancers, it will allow for a larger trial to study the effects of the LDCT surveillance program on lung cancer survival.

The study question aims to determine whether for survivors after curative surgery for Stage I and Stage II lung cancer, a structured Surveillance Program with Low Dose CT can increase the rate of detection and treatment of recurring or new cancers when compared to historical non-structured surveillance with CXR. This study will also determine if it is warranted to pursue a larger scale randomized controlled trial to further investigate optimal LDCT surveillance follow-up intervals and long-term lung cancer survival.

Does Intense Regimented Surveillance Improve the Rates of Therapeutic Re-Intervention After Lung Cancer Surgery

Does Intense Regimented Surveillance Improve the Rates of Therapeutic Re-Intervention After Lung Cancer Surgery: A Pilot Study for the Intense-CT Trial

Defined by: 1) rate of curative intent radiation treatment after detection of recurrent or new primary lung cancer 2) rate of curative intent reoperation after detection of recurrent or new primary lung cancer. Measured by frequency of events.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
This Study Will Evaluate the Effect of Canakinumab or Pembrolizumab Given as Monotherapy or in Combination as Neo-adjuvant Treatment for Subjects With Early Stages NSCLC.	NCT03968419	Non-small Cell ...	Canakinumab Pembrolizumab	18 Years -	Novartis
Treating Early-stage Non-Small Cell Lung Cancer With Durvalumab and Radiation Therapy	NCT04716946	NSCLC Non-small Cell ... Lung Cancer Non-small Cell ... Non-small Cell ... Non-small Cell ... Non-small Cell ... PD-L1 Gene Muta...	Durvalumab Stereotactic Bo...	18 Years -	Memorial Sloan Kettering Cancer Center
Does Intense Regimented Surveillance Improve the Rates of Therapeutic Re-Intervention After Lung Cancer Surgery	NCT02149576	Lung Neoplasms	Low Dose Comput... Chest Radiograp...	18 Years -	McMaster University

Spots Global Cancer Trial Database for early stage nsclc