Trial Outcomes & Findings for Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Non-small Cell Lung Cancer (NCT NCT03647488)

Last Updated: 2022-01-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

18 participants

Primary outcome timeframe

From the day of the first dose of study medication up to 56 days

Results posted on

2022-01-24

Participant Flow

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

Participant milestones

Participant milestones
Measure	Run-in Part: Capmatinib + Spartalizumab 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	Randomized Part: Capmatinib + Spartalizumab 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	Randomized Part: Docetaxel 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
Overall Study STARTED	18	0	0
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	18	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Run-in Part: Capmatinib + Spartalizumab 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	Randomized Part: Capmatinib + Spartalizumab 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	Randomized Part: Docetaxel 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
Overall Study Progressive disease	10	0	0
Overall Study Adverse Event	5	0	0
Overall Study Clinical progression	2	0	0
Overall Study Participant refused to take investigational product	1	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Capmatinib + Spartalizumab 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	Randomized Part: Docetaxel 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	Total n=18 Participants Total of all reporting groups
Age, Continuous	61.2 Years STANDARD_DEVIATION 10.52 • n=5 Participants	—	—	61.2 Years STANDARD_DEVIATION 10.52 • n=4 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	11 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	11 Participants n=4 Participants
Race/Ethnicity, Customized White	17 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	17 Participants n=4 Participants
Race/Ethnicity, Customized Missing	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: From the day of the first dose of study medication up to 56 days

Population: 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).

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)	1 Participants	—

PRIMARY outcome

Timeframe: From the day of the 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 maximum duration of approximately 1.7 years

Population: 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).

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs- All grades	18 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs- Grade ≥3	11 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment-related AEs- All grades	14 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment related AEs- Grade ≥3	1 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Serious AEs (SAEs)- All grades	10 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) SAEs- Grade ≥3	7 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment-related SAEs- All grades	3 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment-related SAEs- Grade ≥3	0 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Fatal SAEs- All grades	1 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Fatal SAEs- Grade ≥3	1 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs leading to discontinuation- All grades	5 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs leading to discontinuation- Grade ≥3	3 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment-related AEs leading to discontinuation- All grades	3 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) Treatment-related AEs leading to discontinuation- Grade ≥3	1 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs leading to dose adjustment/interruption- All grades	9 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs leading to dose adjustment/interruption- Grade ≥3	5 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs requiring additional therapy- All grades	16 Participants	—
Run-in Part: Percentage of Participants With Adverse Events (AEs) AEs requiring additional therapy- Grade ≥3	8 Participants	—

PRIMARY outcome

Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

Population: 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).

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Run-in Part: Percentage of Participants With at Least One Dose Reduction.	6 Participants	—

PRIMARY outcome

Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

Population: 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).

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Run-in Part: Percentage of Participants With at Least One Dose Interruption Capmatinib	8 Participants	—
Run-in Part: Percentage of Participants With at Least One Dose Interruption Spartalizumab	3 Participants	—

PRIMARY outcome

Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

Population: 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).

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Run-in Part: Relative Dose Intensity Received by Participants Capmatinib	99.6 Percentage of dose received Interval 27.8 to 100.0	—
Run-in Part: Relative Dose Intensity Received by Participants Spartalizumab	100.0 Percentage of dose received Interval 75.0 to 133.3	—

PRIMARY outcome

Timeframe: From start of treatment to death due to any cause, assessed until the end of the study (up to a planned duration of 18 months)

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

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

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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment	0 Percentage of participants Interval 0.0 to 18.5	—

SECONDARY outcome

Timeframe: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

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

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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment	27.8 Percentage of participants Interval 9.7 to 53.5	—

SECONDARY outcome

Timeframe: From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part)

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

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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
Progression Free Survival (PFS)	1.9 Months Interval 1.7 to 3.6	—

SECONDARY outcome

Timeframe: From start of treatment to the first documented response of either complete response or partial response, assessed up to 68 weeks (run-in part)

Population: No data available as no participants had event

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first documented response (CR or PR) to first documented progression or death, whichever came first, assessed up to 68 weeks (run-in part)

Population: No data available as no participants had event

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

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days

Population: 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 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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=8 Participants 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	Randomized Part: Docetaxel 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
AUClast of Capmatinib	11500 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 47.3	—

SECONDARY outcome

Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days

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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=5 Participants 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	Randomized Part: Docetaxel 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
AUCtau of Capmatinib	12800 nanogramhour/milliliter (nghr/mL) Geometric Coefficient of Variation 48.5	—

SECONDARY outcome

Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=8 Participants 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	Randomized Part: Docetaxel 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
Maximum Plasma Concentration (Cmax) of Capmatinib	3260 nanogram/milliliter (ng/mL) Geometric Coefficient of Variation 44.6	—

SECONDARY outcome

Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=8 Participants 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	Randomized Part: Docetaxel 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
Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib	1.42 hour (h) Interval 0.983 to 2.0	—

SECONDARY outcome

Timeframe: CCycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days

Population: 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 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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=7 Participants 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	Randomized Part: Docetaxel 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
AUClast of Spartlizumab	1720 microgramday/milliliter (μgday/mL) Geometric Coefficient of Variation 64.5	—

SECONDARY outcome

Timeframe: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days

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.

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=7 Participants 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	Randomized Part: Docetaxel 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
AUCtau of Spartlizumab	2110 microgramday/milliliter (μgday/mL) Geometric Coefficient of Variation 35.1	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=8 Participants 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	Randomized Part: Docetaxel 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
Maximum Plasma Concentration (Cmax) of Spartlizumab	138 microgram/milliliter (μg/mL) Geometric Coefficient of Variation 23.2	—

SECONDARY outcome

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=8 Participants 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	Randomized Part: Docetaxel 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
Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab	1.13 hour (h) Interval 1.0 to 1.53	—

SECONDARY outcome

Timeframe: Cycle 1 Day 1 at predose. Each Cycle is 28 days

Population: 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

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=17 Participants 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	Randomized Part: Docetaxel 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
Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline	3 Participants	—

SECONDARY outcome

Timeframe: Predose at Cycle (C)1 Day (D)1, C2D1, C3D1, C4D1, C6D1, C8D1, C10D1, C12D1, thereafter every 6 cycles until discontinuation, and end of treatment (EOT), 30-day and 150-day after EOT

Population: 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.

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)

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=14 Participants 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	Randomized Part: Docetaxel 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
Spartalizumab ADA Incidence On-treatment	3 Participants	—

POST_HOC outcome

Timeframe: On-treatment deaths: up to approximately 1.7 years. All deaths: up to approximately 1.7 years

Population: 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.

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

Outcome measures

Outcome measures
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 Participants 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	Randomized Part: Docetaxel 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
All Collected Deaths Total Deaths	12 Participants	—
All Collected Deaths Deaths on-treatment	5 Participants	—

Adverse Events

Run-in Part: Capmatinib + Spartalizumab

Serious events: 10 serious events

Other events: 18 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 participants at risk 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
Cardiac disorders Cardiac failure congestive	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Cardiac disorders Ventricular arrhythmia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Fatigue	16.7% 3/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders General physical health deterioration	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Pyrexia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Immune system disorders Anaphylactic reaction	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Immune system disorders Drug hypersensitivity	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Abdominal infection	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Pneumonia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Respiratory tract infection	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Decreased appetite	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Bronchial obstruction	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Vascular disorders Deep vein thrombosis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.

Other adverse events

Other adverse events
Measure	Run-in Part: Capmatinib + Spartalizumab n=18 participants at risk 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
Blood and lymphatic system disorders Anaemia	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Cardiac disorders Pericardial effusion	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Cardiac disorders Stress cardiomyopathy	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Eye disorders Eyelid oedema	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Cheilitis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Constipation	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Diarrhoea	27.8% 5/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Dry mouth	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Dyspepsia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Dysphagia	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Nausea	38.9% 7/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Stomatitis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Gastrointestinal disorders Vomiting	27.8% 5/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Asthenia	22.2% 4/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Axillary pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Chest pain	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Fatigue	22.2% 4/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Oedema peripheral	22.2% 4/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
General disorders Pyrexia	22.2% 4/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Herpes zoster	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Osteomyelitis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Infections and infestations Pneumonia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Alanine aminotransferase increased	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Amylase increased	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Aspartate aminotransferase increased	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Blood alkaline phosphatase increased	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Blood creatinine increased	27.8% 5/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Blood magnesium decreased	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations C-reactive protein increased	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Creatinine renal clearance decreased	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Gamma-glutamyltransferase increased	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Lipase increased	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Lymphocyte count decreased	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Investigations Weight decreased	16.7% 3/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Decreased appetite	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Dehydration	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Hyperglycaemia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Hypoalbuminaemia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Musculoskeletal and connective tissue disorders Arthralgia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Musculoskeletal and connective tissue disorders Muscle spasms	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Nervous system disorders Dizziness	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Nervous system disorders Dysgeusia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Nervous system disorders Headache	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Nervous system disorders Lethargy	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Nervous system disorders Somnolence	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Psychiatric disorders Anxiety	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Psychiatric disorders Confusional state	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Psychiatric disorders Depression	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Psychiatric disorders Sleep disorder	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Renal and urinary disorders Renal pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Reproductive system and breast disorders Nipple pain	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Bronchospasm	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Cough	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea	27.8% 5/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Respiratory, thoracic and mediastinal disorders Productive cough	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Skin and subcutaneous tissue disorders Pruritus	11.1% 2/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Skin and subcutaneous tissue disorders Rash macular	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.
Vascular disorders Hypotension	5.6% 1/18 • On-treatment deaths due to any cause and adverse events 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. 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.

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