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VISION Trial

VISION: A single-arm, open-label, multicenter, non-randomized, multicohort study1


Trial design

The efficacy of TEPMETKO® (tepotinib) was evaluated in adult patients with advanced or metastatic non-small cell lung cancer (NSCLC) harboring METex14 skipping alterations.

Eligibility:

Advanced, metastatic METex14+ NSCLC*

EGFR wild-type and ALK-negative status

≥1 measurable lesion by RECIST v1.1

ECOG PS 0-1

Exclusions:

Symptomatic CNS metastases

Clinically significant uncontrolled cardiac disease

Prior treatment with any MET or HGF inhibitor

 

Eligibility:

Advanced, metastatic METex14+ NSCLC*

EGFR wild-type and ALK-negative status

≥1 measurable lesion by RECIST v1.1

ECOG PS 0-1

Exclusions:

Symptomatic CNS metastases

Clinically significant uncontrolled cardiac disease

Prior treatment with any MET or HGF inhibitor

Treatment-naïve patients (n=69)
Previously treated patients (n=83)

Chart showing TEPMETKO® (tepotinib) VISION trial eligibility, exclusions, and efficacy outcomes

TEPMETKO was administered until disease progression or unacceptable toxicity.

Major efficacy outcome

Confirmed ORR by RECIST v1.1 as evaluated by BIRC

Additional efficacy outcome

DOR by BIRC

 

*Identification of METex14 skipping alterations was prospectively determined using central laboratories employing either a PCR-based or next-generation sequencing-based clinical trial assay using tissue (58%) and/or plasma (65%) samples. An FDA-approved test for detection of METex14 skipping alterations in NSCLC for selecting patients for treatment with TEPMETKO is not available.

Patient characteristics

Patients studied in the VISION Trial (N=152)1-4
 

Disease characteristics

98% of patients had metastatic disease
86% had adenocarcinoma histology
10% had CNS metastases

Age/ECOG status


Median age of 73 years 
(range 41-94)
82% were ≥65
27% had ECOG Performance Status (PS) 0 and 73% had ECOG PS 1

Line of therapy


45% first line (n=69)
55% previously treated (n=83)
– 89% prior platinum-based therapy
– 47% immune-based therapy
Race and Gender


71% White
25% Asian
52% male
48% female
Smoking status


43% never smokers
52% former smokers

 

Disease characteristics

98% of patients had metastatic disease
86% had adenocarcinoma histology
10% had CNS metastases

Age/ECOG status

Median age of 73 years 
(range 41-94)

82% were ≥65

27% had ECOG Performance Status (PS) 0 and 73% had ECOG PS 1

Line of therapy

45% first line (n=69)
55% previously treated (n=83)
 89% prior platinum-based therapy
 47% immune-based therapy
Race and Gender

71% White
25% Asian
52% male
48% female
Smoking status

43% never smokers
52% former smokers


Had progressed on up to 2 lines of prior systemic therapies


MET
ex14 skipping alterations were identified through either PCR or next-generation sequencing (NGS) testing1‡

  • 58% of patients by tissue (RNA-based) testing
  • 65% of patients by plasma (ctDNA-based) testing

 

Some patients tested positive using both methodologies.

ALK=anaplastic lymphoma kinase; BIRC=Blinded Independent Review Committee; CNS=central nervous system; ctDNA=circulating tumor deoxyribonucleic acid; DOR=duration of response; ECOG PS=Eastern Cooperative Oncology Group Performance Status; EGFR=epidermal growth factor receptor; HGF=hepatocyte growth factor; ORR=overall response rate; PCR=polymerase chain reaction; QD=once daily; RECIST=Response Evaluation Criteria in Solid Tumors.
 

IMPORTANT SAFETY INFORMATION AND INDICATION

TEPMETKO can cause interstitial lung disease (ILD)/pneumonitis, which can be fatal. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever). Immediately withhold TEPMETKO in patients with suspected ILD/pneumonitis and permanently discontinue if no other potential causes of ILD/pneumonitis are identified. ILD/pneumonitis occurred in 2.2% of patients treated with TEPMETKO, with one patient experiencing a Grade 3 or higher event; this event resulted in death.

TEPMETKO can cause hepatotoxicity, which can be fatal. Monitor liver function tests (including ALT, AST, and total bilirubin) prior to the start of TEPMETKO, every 2 weeks during the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop increased transaminases or total bilirubin. Based on the severity of the adverse reaction, withhold, dose reduce, or permanently discontinue TEPMETKO. Increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST) occurred in 13% of patients treated with TEPMETKO. Grade 3 or 4 increased ALT/AST occurred in 4.2% of patients. A fatal adverse reaction of hepatic failure occurred in one patient (0.2%). The median time-to-onset of Grade 3 or higher increased ALT/AST was 30 days (range 1 to 178).

TEPMETKO can cause embryo-fetal toxicity. Based on findings in animal studies and its mechanism of action, TEPMETKO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential or males with female partners of reproductive potential to use effective contraception during treatment with TEPMETKO and for one week after the final dose.

Avoid concomitant use of TEPMETKO with dual strong CYP3A inhibitors and P-gp inhibitors and strong CYP3A inducers. Avoid concomitant use of TEPMETKO with certain P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

Fatal adverse reactions occurred in one patient (0.4%) due to pneumonitis, one patient (0.4%) due to hepatic failure, and one patient (0.4%) due to dyspnea from fluid overload.

Serious adverse reactions occurred in 45% of patients who received TEPMETKO. Serious adverse reactions in >2% of patients included pleural effusion (7%), pneumonia (5%), edema (3.9%), dyspnea (3.9%), general health deterioration (3.5%), pulmonary embolism (2%), and musculoskeletal pain (2%).

The most common adverse reactions (≥20%) in patients who received TEPMETKO were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea.

Clinically relevant adverse reactions in <10% of patients who received TEPMETKO included ILD/pneumonitis, rash, fever, dizziness, pruritus, and headache.

Selected laboratory abnormalities (≥20%) from baseline in patients receiving TEPMETKO in descending order were: decreased albumin (76%), increased creatinine (55%), increased alkaline phosphatase (ALP) (50%), decreased lymphocytes (48%), increased ALT (44%), increased AST (35%), decreased sodium (31%), decreased hemoglobin (27%), increased potassium (25%), increased gamma-glutamyltransferase (GGT) (24%), increased amylase (23%), and decreased leukocytes (23%).

The most common Grade 3-4 laboratory abnormalities (≥2%) in descending order were: decreased lymphocytes (11%), decreased albumin (9%), decreased sodium (8%), increased GGT (5%), increased amylase (4.6%), increased ALT (4.1%), increased AST (2.5%), and decreased hemoglobin (2%).

A clinically relevant laboratory abnormality in <20% of patients who received TEPMETKO was increased lipase in 18% of patients, including 3.7% Grades 3 to 4.

INDICATION

TEPMETKO is indicated for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Please see the full Prescribing Information and Medication Guide for additional Important Safety Information for TEPMETKO.

References: 1. TEPMETKO [prescribing information]. EMD Serono, Inc., Rockland, MA; 2021. 2. Paik PK, Felip E, Veillon R, et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations. N Engl J Med. 2020;383:931-943. doi:10.1056/NEJMoa2004407. 3. Paik PK, Felip E, Veillon R, et al. Tepotinib in non–small-cell lung cancer with MET exon 14 skipping mutations [supplementary appendix]. N Engl J Med. 2020;383:931-943. doi:10.1056/NEJMoa2004407. 4. Data on file. Rockland, MA: EMD Serono, Inc.