NCT03647488

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

Completed Phase 2 Results posted Last updated 24 January 2022

What this trial tests

Phase 2 trial testing Capmatinib in Carcinoma, Non-Small-Cell Lung in 18 participants. Completed in 7 September 2020.

Timeline

26 December 2018

Primary endpoint
7 September 2020

7 September 2020

Quick facts

Lead sponsor	Novartis Pharmaceuticals
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	18
Start date	26 December 2018
Primary completion	7 September 2020
Estimated completion	7 September 2020
Sites	8 locations across France, Belgium, Israel, Germany, United States, Spain

Drugs / interventions tested

• Capmatinib (CAPMATINIB) — full drug profile →
• Spartalizumab — full drug profile →
• Docetaxel (Docetaxel) — full drug profile →

Conditions studied

• Carcinoma, Non-Small-Cell Lung — all drugs for Carcinoma, Non-Small-Cell Lung →

Sponsor

Novartis Pharmaceuticals — full company profile →

Who can join

18 and older, any sex, with Carcinoma, Non-Small-Cell Lung. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) Primary · From the day of the first dose of study medication up to 56 days

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.

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	1

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

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

AEs- All grades

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	18

AEs- Grade ≥3

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	11

Treatment-related AEs- All grades

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	14

Treatment related AEs- Grade ≥3

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	1

Serious AEs (SAEs)- All grades

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	10

SAEs- Grade ≥3

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	7

Treatment-related SAEs- All grades

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	3

Treatment-related SAEs- Grade ≥3

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	0

Run-in Part: Percentage of Participants With at Least One Dose Reduction. Primary · From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

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

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	6

Run-in Part: Percentage of Participants With at Least One Dose Interruption Primary · From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

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

Capmatinib

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	8

Spartalizumab

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	3

Run-in Part: Relative Dose Intensity Received by Participants Primary · From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks

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

Capmatinib

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	99.6	27.8 – 100.0

Spartalizumab

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	100.0	75.0 – 133.3

Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment Secondary · From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

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 pa

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	0	0.0 – 18.5

Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment Secondary · From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)

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

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	27.8	9.7 – 53.5

Progression Free Survival (PFS) Secondary · From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part)

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 di

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	1.9	1.7 – 3.6

AUClast of Capmatinib Secondary · Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days

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.

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	11500	± 47.3

AUCtau of Capmatinib Secondary · 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.

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	12800	± 48.5

Maximum Plasma Concentration (Cmax) of Capmatinib Secondary · 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.

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	3260	± 44.6

Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib Secondary · 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.

Group	Value	95% CI
Run-in Part: Capmatinib + Spartalizumab	1.42	0.983 – 2.00

Adverse events — posted to ClinicalTrials.gov

Time frame: 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.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Run-in Part: Capmatinib + Spartalizumab

Serious: 10/18 (56%)

Deaths: 5/18

Serious adverse events (16 terms)

Reaction	System	Run-in Part: Capmatinib + …
Fatigue	General disorders	—
Cardiac failure congestive	Cardiac disorders	—
Ventricular arrhythmia	Cardiac disorders	—
General physical health deterioration	General disorders	—
Pyrexia	General disorders	—
Anaphylactic reaction	Immune system disorders	—
Drug hypersensitivity	Immune system disorders	—
Abdominal infection	Infections and infestations	—
Pneumonia	Infections and infestations	—
Respiratory tract infection	Infections and infestations	—
Decreased appetite	Metabolism and nutrition disorders	—
Bronchial obstruction	Respiratory, thoracic and mediastinal disorders	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Haemoptysis	Respiratory, thoracic and mediastinal disorders	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—
Deep vein thrombosis	Vascular disorders	—

Other adverse events (68 terms — click to expand)

Reaction	System	Run-in Part: Capmatinib + …
Nausea	Gastrointestinal disorders	—
Diarrhoea	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Blood creatinine increased	Investigations	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—
Asthenia	General disorders	—
Fatigue	General disorders	—
Oedema peripheral	General disorders	—
Pyrexia	General disorders	—
Weight decreased	Investigations	—
Anaemia	Blood and lymphatic system disorders	—
Constipation	Gastrointestinal disorders	—
Dysphagia	Gastrointestinal disorders	—
Chest pain	General disorders	—
Alanine aminotransferase increased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
C-reactive protein increased	Investigations	—
Lipase increased	Investigations	—
Lymphocyte count decreased	Investigations	—
Decreased appetite	Metabolism and nutrition disorders	—
Anxiety	Psychiatric disorders	—
Pleural effusion	Respiratory, thoracic and mediastinal disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Pericardial effusion	Cardiac disorders	—
Stress cardiomyopathy	Cardiac disorders	—
Eyelid oedema	Eye disorders	—
Abdominal pain	Gastrointestinal disorders	—
Cheilitis	Gastrointestinal disorders	—
Dry mouth	Gastrointestinal disorders	—
Dyspepsia	Gastrointestinal disorders	—
Stomatitis	Gastrointestinal disorders	—
Axillary pain	General disorders	—
Pain	General disorders	—
Herpes zoster	Infections and infestations	—
Osteomyelitis	Infections and infestations	—
Pneumonia	Infections and infestations	—
Amylase increased	Investigations	—
Blood alkaline phosphatase increased	Investigations	—
Blood magnesium decreased	Investigations	—
Creatinine renal clearance decreased	Investigations	—

Most-reported serious reactions: Fatigue, Cardiac failure congestive, Ventricular arrhythmia, General physical health deterioration, Pyrexia, Anaphylactic reaction, Drug hypersensitivity, Abdominal infection.

Data from ClinicalTrials.gov NCT03647488 adverse events section.

Sponsor's own description

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

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. MET Oncogene in Non-Small Cell Lung Cancer: Mechanism of MET Dysregulation and Agents Targeting the HGF/c-Met Axis.
   Liang H, Wang M. · · 2020 · cited 89× · PMID 32273721 · DOI 10.2147/ott.s231257
2. Revolutionization in Cancer Therapeutics via Targeting Major Immune Checkpoints PD-1, PD-L1 and CTLA-4.
   Pandey P, Khan F, Qari HA, Upadhyay TK, et al · · 2022 · cited 67× · PMID 35337133 · DOI 10.3390/ph15030335
3. A narrative review of MET inhibitors in non-small cell lung cancer with <i>MET</i> exon 14 skipping mutations.
   Santarpia M, Massafra M, Gebbia V, D'Aquino A, et al · · 2021 · cited 44× · PMID 33889528 · DOI 10.21037/tlcr-20-1113
4. NSCLC as the Paradigm of Precision Medicine at Its Finest: The Rise of New Druggable Molecular Targets for Advanced Disease.
   Michelotti A, de Scordilli M, Bertoli E, De Carlo E, et al · · 2022 · cited 24× · PMID 35743191 · DOI 10.3390/ijms23126748
5. Targeting MET in Non-Small Cell Lung Cancer (NSCLC): A New Old Story?
   Spagnolo CC, Ciappina G, Giovannetti E, Squeri A, et al · · 2023 · cited 21× · PMID 37373267 · DOI 10.3390/ijms241210119
6. Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment.
   Yao S, Liu X, Feng Y, Li Y, et al · · 2024 · cited 16× · PMID 39201787 · DOI 10.3390/ijms25169101
7. Spotlight on Tepotinib and Capmatinib for Non-Small Cell Lung Cancer with MET Exon 14 Skipping Mutation.
   Brazel D, Zhang S, Nagasaka M. · · 2022 · cited 15× · PMID 35592355 · DOI 10.2147/lctt.s360574
8. Treatment of Rare Mutations in Patients with Lung Cancer.
   Taha T, Khoury R, Brenner R, Nasrallah H, et al · · 2021 · cited 9× · PMID 34064757 · DOI 10.3390/biomedicines9050534