Trial Outcomes & Findings for 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. (NCT NCT03968419)

Last Updated: 2024-06-20

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

88 participants

Primary outcome timeframe

At time of surgery (up to 6 weeks after first dose of study treatment)

Results posted on

2024-06-20

Participant Flow

The study was conducted in 29 centers across 12 countries.

Screening assessments were done within 28 days prior to randomization. A total of 163 participants were screened. Of them, 88 participants were randomized. After treatment completion or discontinuation, all subjects were followed for safety for up to 130 days following the last dose of study treatment (safety follow-up period).

Participant milestones

Participant milestones
Measure	Canakinumab Monotherapy Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Treatment Period STARTED	35	35	18
Treatment Period COMPLETED	35	35	17
Treatment Period NOT COMPLETED	0	0	1
Safety Follow-up Period STARTED	35	35	18
Safety Follow-up Period COMPLETED	30	32	17
Safety Follow-up Period NOT COMPLETED	5	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Canakinumab Monotherapy Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Treatment Period Adverse Event	0	0	1
Safety Follow-up Period Death	3	2	1
Safety Follow-up Period Subject Decision	2	1	0

Baseline Characteristics

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.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy n=18 Participants Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery	Total n=88 Participants Total of all reporting groups
Age, Continuous	65.5 Years STANDARD_DEVIATION 9.88 • n=93 Participants	67.1 Years STANDARD_DEVIATION 6.98 • n=4 Participants	66.1 Years STANDARD_DEVIATION 5.61 • n=27 Participants	66.2 Years STANDARD_DEVIATION 7.99 • n=483 Participants
Sex: Female, Male Female	13 Participants n=93 Participants	14 Participants n=4 Participants	9 Participants n=27 Participants	36 Participants n=483 Participants
Sex: Female, Male Male	22 Participants n=93 Participants	21 Participants n=4 Participants	9 Participants n=27 Participants	52 Participants n=483 Participants
Race/Ethnicity, Customized White	20 Participants n=93 Participants	25 Participants n=4 Participants	12 Participants n=27 Participants	57 Participants n=483 Participants
Race/Ethnicity, Customized Asian	7 Participants n=93 Participants	3 Participants n=4 Participants	2 Participants n=27 Participants	12 Participants n=483 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race/Ethnicity, Customized Unknown	7 Participants n=93 Participants	5 Participants n=4 Participants	4 Participants n=27 Participants	16 Participants n=483 Participants

PRIMARY outcome

Timeframe: At time of surgery (up to 6 weeks after first dose of study treatment)

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
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	2.9 Percentage of participants Interval 0.07 to 14.92	17.1 Percentage of participants Interval 6.56 to 33.65	—

SECONDARY outcome

Timeframe: Predose (0 hour) on Day 1 of Cycle 1 (Cycle=21 days)

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

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Canakinumab Antidrug Antibodies (ADA) Prevalence	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From baseline (Predose on Day 1 of Cycle 1) up to 130 days after last dose of study treatment (assessed up to 24.6 weeks). Cycle = 21 days

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

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)

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Canakinumab ADA Incidence	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Predose (0 hour) on Day 1 of Cycle 1 (Cycle = 21 days)

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

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=18 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Pembrolizumab ADA Prevalence	4 Participants	3 Participants	—

SECONDARY outcome

Timeframe: From baseline (Predose on Day 1 of Cycle 1) up to 26 days after last dose of study treatment (assessed up to 10.7 weeks). Cycle = 21 days

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

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)

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=18 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Pembrolizumab ADA Incidence	3 Participants	4 Participants	—

SECONDARY outcome

Timeframe: From date of randomization to date of surgery, assessed up to 6 weeks

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

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy n=18 Participants Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Overall Response Rate (ORR) Based on Local Investigator Assessment Using RECIST v1.1	0 Percentage of participants Interval 0.0 to 10.0	8.6 Percentage of participants Interval 1.8 to 23.06	11.1 Percentage of participants Interval 1.38 to 34.71

SECONDARY outcome

Timeframe: Predose (0 hour) on Day 1 of Cycles 1 and 2 (Cycle =21 days)

Population: 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

Canakinumab serum concentrations were determined at the specified time points.

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Serum Canakinumab Concentration Cycle 2	10.9 microgram/miliLiter (ug/mL) Geometric Coefficient of Variation 32.9	10.3 microgram/miliLiter (ug/mL) Geometric Coefficient of Variation 41.0	—
Serum Canakinumab Concentration Cycle 1	0 microgram/miliLiter (ug/mL) Geometric Coefficient of Variation 0	0 microgram/miliLiter (ug/mL) Geometric Coefficient of Variation 0	—

SECONDARY outcome

Timeframe: Predose (0 hour) and 0.5 hours post dose on Day 1 of Cycle 1 and predose on Cycle 2 (Cycle =21 days)

Population: 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

Pembrolizumab serum concentrations were determined at the specified time points.

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=34 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=17 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Serum Pembrolizumab Concentration Cycle 1 predose	0 ug/mL Geometric Coefficient of Variation 0	0 ug/mL Geometric Coefficient of Variation 0	—
Serum Pembrolizumab Concentration Cyle 1 0.5 hours post dose	65.5 ug/mL Geometric Coefficient of Variation 23.8	65.5 ug/mL Geometric Coefficient of Variation 19.9	—
Serum Pembrolizumab Concentration Cycle 2 predose	16.0 ug/mL Geometric Coefficient of Variation 43.4	35.5 ug/mL Geometric Coefficient of Variation 13.7	—

SECONDARY outcome

Timeframe: Up to 6 weeks after first dose

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

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy n=18 Participants Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Surgical Feasibility Rate	91.4 Percentage of participants Interval 76.94 to 98.2	97.1 Percentage of participants Interval 85.08 to 99.93	100 Percentage of participants Interval 81.47 to 100.0

SECONDARY outcome

Timeframe: At time of surgery (up to 6 weeks after first dose)

Population: All subjects who were randomized to pembrolizumab monotherapy arm

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.

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=18 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Major Pathological Response (MPR) Rate at the Time of Surgery in Subjects Randomized to Pembrolizumab Monotherapy Based on Central Review	16.7 Percentage of participants Interval 3.58 to 41.42	—	—

SECONDARY outcome

Timeframe: At time of surgery (up to 6 weeks after first dose of study treatment)

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

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.

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=18 Participants 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	Pembrolizumab Monotherapy Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Difference in Major Pathological Response (MPR) Rate Between the Canakinumab Plus Pembrolizumab Arm and the Pembrolizumab Arm Based on Central Review	17.1 Percentage of participants Interval 6.56 to 33.65	16.7 Percentage of participants Interval 3.58 to 41.42	—

SECONDARY outcome

Timeframe: At time of surgery (up to 6 weeks after first dose)

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

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy n=18 Participants Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Major Pathological Response (MPR) Rate at the Time of Surgery in All Subjects Based on Local Review	0 Percentage of participants Interval 0.0 to 10.0	20.0 Percentage of participants Interval 8.44 to 36.94	22.2 Percentage of participants Interval 6.41 to 47.64

SECONDARY outcome

Timeframe: From date of randomization up to 6 weeks after first dose

Population: 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

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.

Outcome measures

Outcome measures
Measure	Canakinumab Monotherapy n=35 Participants Participants received 200 mg of canakinumab once every 3 weeks for a maximum duration of 6 weeks prior to surgery	Canakinumab + Pembrolizumab n=35 Participants 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	Pembrolizumab Monotherapy n=18 Participants Participants received 200 mg of pembrolizumab every 3 weeks for a maximum duration of 6 weeks prior to surgery
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers CD8: <3%	0 Percentage of participants Interval 0.0 to 26.46	13.0 Percentage of participants Interval 2.78 to 33.59	0 Percentage of participants Interval 0.0 to 52.18
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers CD8: >=3%	0 Percentage of participants Interval 0.0 to 18.53	22.2 Percentage of participants Interval 2.81 to 60.01	33.3 Percentage of participants Interval 4.33 to 77.72
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers PD-L1: <1%	0 Percentage of participants Interval 0.0 to 26.46	7.1 Percentage of participants Interval 0.18 to 33.87	14.3 Percentage of participants Interval 0.36 to 57.87
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers PD-L1: 1-49%	6.7 Percentage of participants Interval 0.17 to 31.95	15.4 Percentage of participants Interval 1.92 to 45.45	16.7 Percentage of participants Interval 0.42 to 64.12
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers PD-L1: >=50%	0 Percentage of participants Interval 0.0 to 45.93	42.9 Percentage of participants Interval 9.9 to 81.59	0 Percentage of participants Interval 0.0 to 70.76
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-CRP: <2mg/L	12.5 Percentage of participants Interval 0.32 to 52.65	7.7 Percentage of participants Interval 0.19 to 36.03	37.5 Percentage of participants Interval 8.52 to 75.51
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-CRP: >=2mg/L	0 Percentage of participants Interval 0.0 to 13.23	22.7 Percentage of participants Interval 7.82 to 45.37	0 Percentage of participants Interval 0.0 to 33.63
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-IL-6: <Q1 (2.52 mg/L)	16.7 Percentage of participants Interval 0.42 to 64.12	12.5 Percentage of participants Interval 0.32 to 52.65	14.3 Percentage of participants Interval 0.36 to 57.87
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-IL-6: >=Q1 (2.52 pg/mL) to <Q2 (5.36 pg/mL)	0 Percentage of participants Interval 0.0 to 36.94	10 Percentage of participants Interval 0.25 to 44.5	33.3 Percentage of participants Interval 0.84 to 90.57
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-IL-6: >=Q2 (5.36 pg/mL) to <Q3 (12.03 pg/mL)	0 Percentage of participants Interval 0.0 to 36.94	28.6 Percentage of participants Interval 3.67 to 70.96	16.7 Percentage of participants Interval 0.42 to 64.12
Major Pathological Response (MPR) Rate Based on the Levels of Biomarkers hs-IL-6: >=Q3 (12.03 pg/mL)	0 Percentage of participants Interval 0.0 to 30.85	20.0 Percentage of participants Interval 2.52 to 55.61	0 Percentage of participants Interval 0.0 to 97.5

Adverse Events

Canakinumab Monotherapy

Serious events: 10 serious events

Other events: 28 other events

Deaths: 3 deaths

Canakinumab + Pembrolizumab

Serious events: 9 serious events

Other events: 27 other events

Deaths: 2 deaths

Pembrolizumab Monotherapy

Serious events: 4 serious events

Other events: 14 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER