Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Lymphoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Mitogens

Spartalizumab

Tubulin Modulators

Antimitotic Agents

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Participants (enrolled in the run-in part) were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days

Participants (enrolled in the randomized part) treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days

Participants (enrolled in the randomized part) treated with docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days

Capmatinib 400 mg (tablets) orally taken twice daily

Capmatinib

Spartalizumab 400 mg via intravenous infusion once every 28 days

Docetaxel 75mg/m2 i.v. following local guidelines as per standard of care and product labels once every 21 days

The purpose of this trial was to evaluate the safety and efficacy of capmatinib in combination with spartalizumab in adult participants with epidermal growth factor receptor (EGFR) wild type (for exon 19 deletions and exon 21 L858R substitution mutations), anaplastic lymphoma kinase (ALK) rearrangement negative in locally advanced (stage IIIB, not eligible for definitive chemo-radiation) or metastatic (stage IV) Non-small cell lung cancer (NSCLC) after failure of platinum doublet and checkpoint inhibitor treatment.

This was a two-part prospectively designed, multicenter, open-label, randomized phase II study.

Part 1: Run-in. Prior to the randomized part of the study, a run-in to assess the safety and tolerability as well as preliminary efficacy of the capmatinib and spartalizumab combination was conducted. Participants were treated with capmatinib 400 mg twice daily (BID) and spartalizumab 400 mg intravenously (i.v.) once every 28 days. A review was planned to take place after all participants had at least 24 weeks of follow-up. The decision to expand the study to the randomized part was to be based on the safety, tolerability, and preliminary efficacy of the capmatinib and spartalizumab combination.

Part 2: Randomized. Subjects were planned to be randomized to one of the following arms in a 2:1 ratio: 1) combination of capmatinib 400 mg BID and spartalizumab 400 mg i.v. once every 28 days; 2) docetaxel 75 mg/m2 i.v. following local guidelines as per standard of care and product labels. Based on the results obtained in the run-in part of the study, the randomized part was not opened.

For the run-in part of the study, the treatment period began on Cycle 1 Day 1 and continued in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of informed consent, pregnancy, lost to follow-up, or death irrespective of start of new anti-neoplastic therapy. After treatment discontinuation, all subjects were followed for safety evaluations during the safety follow-up period, and the subject's status was collected every 8 weeks as part of the survival follow-up

Run-in part was single group. Randomized part (parallel design) was not opened.

Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer

Phase II Multicenter Randomized Two-arm Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Pretreated Adult Patients With EGFR Wild-type ALK Rearrangement Negative Advanced/Metastatic Non-small Cell Lung Cancer

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 review 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 availability is according to the criteria and process described on www.clinicalstudydatarequest.com

A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol.

Percentage of participants with AEs, including changes from baseline in vital signs and laboratory results qualifying and reported as AEs.

AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: Death

Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib

Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab.

The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100.

OS is defined as the time from date of start of treatment to date of death due to any cause. If a participant was not known to have died, survival was censored at the date of last known date patient alive.

Results are not available because randomized part never started.

ORR is defined as the percentage of subjects with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as per investigator assessment.

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.

ORR results for randomized part are not available because randomized part never started.

DCR is defined as the percentage of subjects with best overall response of CR or PR or stable disease based on RECIST 1.1 and as per investigator assessment.

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.

Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

DCR results for randomized part are not available because randomized part never started.

PFS is defined as the time from the date of start of treatment to the date of the first documented radiological progression or death due to any cause. For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.

Progression is defined using RECIST 1.1 and as per investigator assessment as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

PFS results for randomized part are not available because randomized part never started.

TTR is defined as the time from the date of start of treatment to the first documented response of either CR or PR, which must be subsequently confirmed. TTR was evaluated according to RECIST 1.1 and as per investigator assessment.

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.

For run-in part, TTR results are not available because there were no participants achieving response (CR or PR) For randomized part , TTR results are not available because randomized part never started.

DOR is the time between the date of first documented response(CR or PR) and the date of first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator assessment. If progression or death has not occurred, the subject is censored at the date of last adequate tumor assessment. CR: Disappearance of all non-nodal target lesions and 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. Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm. Results are not available because there were no participants achieving response in the run-in part and randomized part never started

AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated using non-compartmental methods.

AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval Tau. AUCtau was calculated using non-compartmental methods.

The maximum (peak) observed plasma concentration after single dose administration. Cmax was calculated using non-compartmental methods.

Tmax is the time to reach maximum (peak) plasma concentration of capmatinib after single dose administration (time). Tmax was calculated using non-compartmental methods.

Tmax is the time to reach maximum (peak) plasma concentration of spartlizumab after single dose administration (time). Tmax was calculated using non-compartmental methods.

ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline

ADA incidence on treatment was calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and 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)

Novartis Pharmaceuticals

Any sign or symptom that occurs during the study treatment plus 150 days after the last dose of spartalizumab or 30 days after the last dose of capmatinib (on-treatment). Total number of deaths are captured in Outcome Measure 22 (post-hoc: all-cause mortality). Analysis performed on the safety set in the run-in part: all participants who received at least one dose of spartalizumab \[including incomplete infusion\] or of capmatinib. No safety data is available for part 2 because it was not opened.

Run-in Part: Capmatinib + Spartalizumab

Randomized Part: Capmatinib + Spartalizumab

Randomized Part: Docetaxel

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

Based on preliminary results of run-in part, randomized part was not opened. Therefore, no participants were enrolled in the randomized part of the study.

Study Director

All participants from the Safety Set in the run-in who experienced DLT during the first 8 weeks of dosing or met the minimum exposure criterion (subject received at least 1 infusion of spartalizumab and took at least 50% of the planned dose of capmatinib within the first 8 weeks of treatment) and had sufficient safety evaluations (subjects were observed for ≥56 days following the first dose, and are considered to have enough safety data to conclude that a DLT did not occur).

Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)

AEs- All grades

AEs- Grade ≥3

Treatment-related AEs- All grades

Treatment related AEs- Grade ≥3

Serious AEs (SAEs)- All grades

SAEs- Grade ≥3

Treatment-related SAEs- All grades

Treatment-related SAEs- Grade ≥3

Fatal SAEs- All grades

Fatal SAEs- Grade ≥3

AEs leading to discontinuation- All grades

AEs leading to discontinuation- Grade ≥3

Treatment-related AEs leading to discontinuation- All grades

Treatment-related AEs leading to discontinuation- Grade ≥3

AEs leading to dose adjustment/interruption- All grades

AEs leading to dose adjustment/interruption- Grade ≥3

AEs requiring additional therapy- All grades

AEs requiring additional therapy- Grade ≥3

All participants in the run-in who received at least one dose of study treatment (i.e. at least one dose of spartalizumab \[including incomplete infusion\] or of capmatinib).

Run-in Part: Percentage of Participants With Adverse Events (AEs)

Run-in Part: Percentage of Participants With at Least One Dose Reduction.

Run-in Part: Percentage of Participants With at Least One Dose Interruption

Run-in Part: Relative Dose Intensity Received by Participants

Data was not collected as no participants were enrolled in randomized part.

Randomized Part: Overall Survival (OS)

All participants in the run-in who received at least one dose of any component of study treatment.

Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment

Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment

Progression Free Survival (PFS)

No data available as no participants had event

Time to Response (TTR) Based on RECIST 1.1 and as Per Investigator Assessment

Duration of Response (DOR) Based on RECIST 1.1 and as Per Investigator Assessment

The capmatinib pharmacokinetic (PK) analysis set included all participants in the run-in phase who provided at least one evaluable capmatinib PK concentration. Only those participants with data available for this endpoint at specified data points were analyzed.

AUClast of Capmatinib

AUCtau of Capmatinib

Maximum Plasma Concentration (Cmax) of Capmatinib

Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib

The spartlizumab pharmacokinetic (PK) analysis set included all participants in the run-in phase who provided at least one evaluable spartlizumab PK concentration. Only those participants with data available for this endpoint at specified data points were analyzed.

AUClast of Spartlizumab

AUCtau of Spartlizumab

Maximum Plasma Concentration (Cmax) of Spartlizumab

Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab

immunogenicity (IG) prevalence set includes all subjects in the Full analysis set with a determinant baseline IG sample or at least one determinant post-baseline sample.

Determinant sample: sample that is neither ADA-inconclusive nor unevaluable

Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline

The IG incidence set includes all subjects in the IG prevalence set with a determinant baseline IG sample and at least one determinant post-baseline IG sample.

Determinant sample: sample that is neither ADA-inconclusive nor unevaluable.

Spartalizumab ADA Incidence On-treatment

Total Deaths

Deaths on-treatment

On-treatment deaths due to any cause were collected from first dose of study medication to 150 days after the last dose of spartalizumab, or 30 days after the last dose of capmatinib, whichever is later, up to a maximum duration of approximately 1.7 years.

Total deaths were collected from first dose of study treatment until end of post-treatment efficacy or survival follow, up to maximum duration of approximately 1.7 years

Safety Set consisted of all participants who received at least one dose of study treatment, i.e. at least one dose of spartalizumab \[including incomplete infusion\] or of capmatinib.

Spots Global Cancer Trial Database for capmatinib and spartalizumab