Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

Patients receive 50Gy/25F, 2Gy/F QD, five days a week for 5 weeks

dose-reduced radiotherapy

Yingpeng Peng, Dr.

This is an open-label, single-arm, phase II clinical trial to explore the efficacy and safety of de-escalation of postoperative radiotherapy in locally advanced head and neck squamous cell carcinoma with pathological complete response/major pathological response to neoadjuvant therapy. The eligible patients are scheduled to administered postoperative radiotherapy, PTV 50Gy/25F, instead of the standard dose of 60Gy. The overall primary study hypothesis is that reducing the dose of postoperative radiotherapy in the specific population does not affect DFS but significantly reduces treatment related adverse events.

The Efficacy and Safety of De-escalated Postoperative Radiotherapy in Locally Advanced HNSCC With pCR/MPR

De-escalation of Postoperative Radiotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma With Pathological Complete Response/Major Pathological Response: A Single-arm, Prospective Phase II Clinical Study

2-year distant metastasis free survival rate

Fifth Affiliated Hospital, Sun Yat-Sen University

Director

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

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

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Tubulin Modulators

Antimitotic Agents

The patients will receive three cycles (one cycle is defined as every 21 days +/- 3 days) of neoadjuvant therapy with camrelizumab 200 mg, nab-paclitaxel 260 mg/m2, and carboplatin AUC 5. This will then be followed by surgery.

Camrelizumab + Nab-paclitaxel + Carboplatin

Herui Yao, PhD

Yunfang Yu, MD

This prospective, single-arm, multicenter, phase II trial enrolled 40 patients who underwent surgery after three cycles of neoadjuvant therapy with camrelizumab, nab-paclitaxel, and carboplatin. The MPR is the primary endpoint, and the pCR, the complete resection rate, the objective response rate, the disease-free survival, adverse events, and quality of life are the secondary endpoints. The exploratory endpoints will be used to establish a multiomics artificial intelligence system for neoadjuvant therapy effect prediction and decision-making assistance based on radiomics, metabolism, genetic, and clinic-pathological characteristics and to explore drug resistance mechanisms.

Neoadjuvant Camrelizumab, Nab-paclitaxel and Carboplatin in Stage IB-IIIA NSCLC

Neoadjuvant Camrelizumab, Nab-paclitaxel and Carboplatin in Patients With Stage IB-IIIA Non-small Cell Lung Cancer (NANE-LC): A Prospective, Single-arm, Multicenter, Phase II Study

MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy.

pCR rate is defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy.

Proportion of patients with no residual resection margin under the microscope after tumor resection

From the date of surgery to any of the following events: disease progression, disease recurrence or death from any cause.

From the date of participated in study to the date of death.

The proportion of patients achieved complete or patial remission(Imageological) according to RECIST 1.1 prior to definitive surgery

The number of participants experiencing an AE will be assessed.An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined

The number of participants experiencing an serious AE will be assessed

Quality of life asscesed by Quality of Life Questionnare-Core 30(EORTC QLQ-C30）of The European O-rganization for Reasearch and Functional Assessment of Cancer Therapy-Lung (FACT-L)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The Efficacy and Safety of De-escalated Postoperative Radiotherapy in Locally Advanced HNSCC With pCR/MPR	NCT05854823	Head and Neck S...	dose-reduced ra...	18 Years - 70 Years	Fifth Affiliated Hospital, Sun Yat-Sen University
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
Neoadjuvant Camrelizumab, Nab-paclitaxel and Carboplatin in Stage IB-IIIA NSCLC	NCT04541251	Lung Cancer, No... Artificial Inte...	Camrelizumab + ...	18 Years -	Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
The Efficacy and Safety of De-escalated Postoperative Radiotherapy in Locally Advanced HNSCC With pCR/MPR	NCT05854823	Head and Neck S...	dose-reduced ra...	18 Years - 70 Years	Fifth Affiliated Hospital, Sun Yat-Sen University

Spots Global Cancer Trial Database for major pathological response