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

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Gland and Hormone Related Diseases

Rare Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Fallopian Tube Neoplasms

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Urogenital Neoplasms

Endocrine System Diseases

Gonadal Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Fallopian Tube Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Fallopian Tube Cancer

Paclitaxel

Carboplatin

Albumin-Bound Paclitaxel

Tubulin Modulators

Antimitotic Agents

Carboplatin AUC= 6 paclitaxel 80 mg/m2 Pembrolizumab 200 mg starting cycle 2

This is a single arm feasibility study in patients with primary FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer to evaluate neo-adjuvant + adjuvant pembrolizumab for its capacity to induce and broaden T cell responses against tumor neo-antigens.

Long-term survival in stage IV serous ovarian, peritoneal, and fallopian tube cancer is poor and has not significantly improved over the last decades. Standard treatment consists of debulking surgery and six courses of carboplatin and paclitaxel. Nevertheless, the disease recurs in \>90% of women, usually within two years.

Since early observations that the presence of infiltrating T cells is associated with improved outcome, ovarian cancer is linked to a potential benefit of immunotherapy.10 More recently, T cell checkpoint blockade with anti-PD1 and anti-PDL1 have shown promising activity in platinum resistant ovarian cancer with objective and durable responses in 10-20% of patients. This finding raises the question whether anti-PD1 could also play a role in first line treatment of ovarian cancer.

To fully use the power of T cell checkpoint inhibition, sufficient TCR stimulation is required. Importantly, the amount of antigen that can provide this signal will correlate with tumor load, and because of this adjuvant immunotherapy may work most efficiently, when initiated prior to surgery. In addition, we postulate that antigen retrieval will increase after induction treatment with cytotoxic therapy.

To address these questions, we propose a feasibility study in patients with FIGO stage IV serous ovarian, peritoneal, or fallopian tube cancer in which we evaluate pembrolizumab added to standard treatment for its capacity to induce and broaden T cell responses against neo-antigens.

Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer

Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer

determine the number of T cells in peripheral blood samples and tissue samples

Toxicity will be analyzed in patients who have received at least one administration of pembrolizumab.

number of patients with no viable invasive tumor left in the resection specimen

Number of patients with partial or complete response according to RECIST

Merck Sharp & Dohme LLC

The Netherlands Cancer Institute

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Cisplatin

Induction Chemotherapy with TPF Then: cisplatin 100 mg/m2 on day 1, 22 and 43 combined with conventional radiotherapy

Induction chemotherapy with TPF Then cisplatin 40mg/m2 on day 1,8,15,22,29 and 35 combined with accelerated radiotherapy

radiotherapy: 5 fractions/week, total treatment time 7 weeks. Dose to gross tumor volume 70 Gy/35 fractions, dose to elective nodal areas 46 Gy/23 fractions.

100 mg/m2 cisplatin iv on day 1, 22 and 43

conventional radiotherapy with 'high' dose cisplatin

Accelerated radiotherapy 6 fractions/week, total treatment time 6 weeks. During one of the weekdays two fractions will be delivered with an interval of at least 6h. Dose to gross tumor volume 70 Gy/35 fractions, dose to elective nodal areas 46 Gy/23 fractions cisplatin 40 mg/m2 iv on day 1,8,18,22,29,35

accelerated radiotherapy with 'low' dose cisplatin

C.M.L. van Herpen, Md, Phd

J.P. de Boer

C.M.L van Herpen, Md, Phd

C.M.L. van Herpen, MD, Phd

The purpose of this trial is to compare two different treatments for fit patients with head and neck cancer:

All patients are given induction-chemotherapy (docetaxel, cisplatin, 5-FU).

Subsequently patients are being randomised into two groups:

* The first group receives neo-adjuvant chemotherapy ('high' dose cisplatin) and conventional radiotherapy
* The second group receives neo-adjuvant chemotherapy ('low' dose cisplatin) and accelerated radiotherapy.

Induction Chemotherapy TPF(arm A and B)

: Docetaxel 75 mg/m2 iv on day 1, Cisplatin 75 mg/ m2 iv on day 1, 5-FU 750 mg/ m2/day iv continuous infusion (in Hickman or port a cath) on days 1-5; prophylactic G-CSF

This cycle will be repeated every 21 days for a maximum of 4 cycles. Clinical evaluation after each cycle and radiological evaluation after 2 cycles will take place. In case of PD or SD (after 2 cycles) with no minor response (no decrease in measurable disease from baseline) concomitant chemoradiotherapy will started per protocol.

Surgery The investigators in each centre can decide neck surgery for residual tumor

TPF Induction With Concomitant Chemoradiation to Treat Patients With Head and Neck Cancer

A Randomised Study of TPF as Neoadjuvant Chemotherapy Followed by Concomitant Chemoradiotherapy (CRT) With Conventional Radiotherapy (RT) Versus Concomitant CRT With Accelerated RT in Patients With Locally Advanced Head and Neck Squamous Cell Cancer (HNSCC) in Good Condition. The Condor Study. A Study of the Dutch Head and Neck Cancer Group (DHNCG).

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
Neo-adjuvant Pembrolizumab in Primary Stage IV Ovarian Cancer	NCT03126812	Ovarian Cancer ... Peritoneal Canc... Fallopian Tube ...	Carboplatin Paclitaxel Pembrolizumab	18 Years -	The Netherlands Cancer Institute
TPF Induction With Concomitant Chemoradiation to Treat Patients With Head and Neck Cancer	NCT00774319	Head and Neck C...	conventional ra... accelerated rad...	18 Years - 65 Years	Radboud University Medical Center

Spots Global Cancer Trial Database for neo adjuvant

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