Effects of tepotinib: A Synthesis of Findings from 18 Studies

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Original Abstract of the Article

Major research findings

Tepotinib is a promising new treatment option for advanced hepatocellular carcinoma (HCC) with MET overexpression. Several studies have shown that tepotinib significantly prolongs the progression-free survival of HCC patients compared to sorafenib. 13 Tepotinib has also been reported to exhibit good efficacy and tolerability in patients with HCC who have previously been treated with sorafenib. 15 Tepotinib has also been shown to be effective in multiple studies for non-small cell lung cancer (NSCLC) with MET exon 14 skipping mutations. 3 18 10 5 While tepotinib is expected to be effective against brain metastasis in NSCLC with MET exon 14 skipping mutations, further research is needed in this area. 5 Tepotinib has been reported to suppress proliferation, invasion, migration, and promote apoptosis of melanoma cells. 16 Tepotinib may also overcome multidrug resistance mediated by ABCB1. 11 In addition, tepotinib, when combined with gefitinib, may prolong progression-free survival in patients with EGFR-mutated NSCLC with MET amplification after progression on EGFR inhibitors. 9 Tepotinib may also change metabolic pathways, which could be used to predict therapeutic efficacy and develop new treatment strategies. 12

Benefits and risks

Benefit summary

Tepotinib has been shown to be effective in multiple studies for advanced HCC with MET overexpression and NSCLC with MET exon 14 skipping mutations. Tepotinib has also been reported to exhibit good efficacy and tolerability in patients with HCC who have previously been treated with sorafenib. Tepotinib has been shown to suppress proliferation, invasion, migration, and promote apoptosis of melanoma cells. In addition, tepotinib may overcome multidrug resistance mediated by ABCB1. Tepotinib, when combined with gefitinib, may prolong progression-free survival in patients with EGFR-mutated NSCLC with MET amplification after progression on EGFR inhibitors.

Risk summary

Tepotinib is generally well tolerated, but some side effects have been reported. The most common side effects include peripheral edema, increased lipase, and elevated liver function tests. 13 15 5 9 Tepotinib may be activated through the generation of iminium intermediates, which may lead to side effects. 6 Tepotinib may also affect neurocognitive function. 5

Comparison between studies

Commonalities between studies

Many studies have confirmed that tepotinib is effective against advanced HCC with MET overexpression and NSCLC with MET exon 14 skipping mutations. Many studies have reported that tepotinib is generally well tolerated.

Differences between studies

The effectiveness, the extent of side effects, and the target patient population vary depending on the study. For example, tepotinib has been reported to be effective in patients with HCC who have previously been treated with sorafenib, but this effect is not clearly established when compared to patients who have not been treated with sorafenib. 15 In addition, tepotinib, when combined with gefitinib, may prolong progression-free survival in patients with EGFR-mutated NSCLC with MET amplification after progression on EGFR inhibitors, but this effect has not been confirmed in all patients. 9

Consistency and contradictions in the results

Multiple studies have confirmed that tepotinib is effective against advanced HCC with MET overexpression and NSCLC with MET exon 14 skipping mutations. However, different results have been reported regarding the effectiveness of tepotinib, the extent of side effects, and the target patient population. These differences may be due to variations in study design, target patient population, and side effect evaluation methods.

Precautions for real-life application

Tepotinib may be a promising treatment option for specific cancers such as advanced HCC with MET overexpression or NSCLC with MET exon 14 skipping mutations. However, tepotinib is not effective for all patients. In addition, some side effects such as peripheral edema, increased lipase, and elevated liver function tests have been reported with tepotinib. When considering the use of tepotinib, it is important to consult with a doctor and understand the risks and benefits.

Limitations of current research

Research on tepotinib is still in its early stages and many aspects remain unclear. For example, further research is needed on tepotinib's long-term effects, safety, optimal dosage, effectiveness against various cancer types, potential combination therapies, and overcoming tepotinib resistance. Many studies on tepotinib are small and the results may not apply to all patients. In addition, there is still insufficient data on the long-term effects and safety of tepotinib.

Future research directions

Further research is needed to better understand the efficacy and side effects of tepotinib. Specifically, research is needed on tepotinib's long-term effects, safety, optimal dosage, effectiveness against various cancer types, potential combination therapies, and overcoming tepotinib resistance. In addition, the development of new therapies to further enhance the effectiveness of tepotinib is also needed.

Conclusion

Tepotinib is a promising treatment option for specific cancers such as advanced HCC with MET overexpression or NSCLC with MET exon 14 skipping mutations. However, tepotinib has some reported side effects and is not effective for all patients. When considering the use of tepotinib, it is important to consult with a doctor and understand the risks and benefits. It is hoped that future research will lead to a better understanding of the efficacy and safety of tepotinib, making it available for safe and effective use by more patients.

Literature analysis of 18 papers
Positive Content
17
Neutral Content
1
Negative Content
0
Article Type
3
0
0
3
17
1.

The prospective randomized study on telaprevir at 1500 or 2250 mg with pegylated interferon plus ribavirin in Japanese patients with HCV genotype 1.

Author: OzeTsugiko, HiramatsuNaoki, YakushijinTakayuki, YamadaRyoko, HaradaNaoki, MorishitaNaoki, YamadaAkira, OshitaMasahide, KanekoAkira, SuzukiKunio, InuiYoshiaki, TamuraShinji, YoshiharaHarumasa, ImaiYasuharu, MiyagiTakuya, YoshidaYuichi, TatsumiTomohide, KasaharaAkinori, HayashiNorio, TakeharaTetsuo

Antiviral efficacy
Adverse effects

Triple therapy with telaprevir (TVR), pegylated interferon, and ribavirin has improved antiviral efficacy in patients with chronic hepatitis C (CH-C). However, TVR causes severe adverse effects. This study examines the antiviral efficacy and safety of reduced administration of TVR in patients with CH-C.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

Effects of boceprevir and telaprevir on the pharmacokinetics of dolutegravir.

Author: JohnsonMark, BorlandJulie, ChenShuguang, SavinaPaul, WynneBrian, PiscitelliStephen

Dolutegravir can be coadministered with boceprevir or telaprevir in patients coinfected with HIV and HCV with no dose adjustment.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

3.

Transient asymptomatic pulmonary opacities in a patient with MET exon 14 skipping non-small cell lung cancer: A case report.

Author: IkeoSatoshi, YasudaNaoaki, SakaiYuki, HayashiYasuyuki, SokaiAkihiko, IwataToshiyuki, NishimuraTakashi

Lung cancer treatment
TAPOs management
GGOs

MET tyrosine kinase inhibitors (MET-TKIs) are used to treat certain lung cancers. This case report describes a patient who developed ground-glass opacities (GGOs) during treatment with tepotinib, a MET-TKI. The GGOs resolved after stopping the drug, and treatment was successfully resumed with a lower dose, suggesting that MET-TKIs may cause transient asymptomatic pulmonary opacities (TAPOs) in some cases.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

4.

[Progress on Mechanism of MET Gene Mutation and Targeted Drugs in Non-small Cell Lung Cancer].

Author: HanSen, MaXu, FangJian

Good safety
MET inhibitor efficacy
Drug resistance

MET inhibitors, such as crizotinib, cabozantinib, savolitinib and tepotinib, are effective for non-small cell lung cancer with MET 14 exon skipping mutation.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : Chinese

5.

Dramatic intracranial response to tepotinib in a patient with lung adenocarcinoma harboring MET exon 14 skipping mutation.

Author: TakamoriShinkichi, MatsubaraTaichi, FujishitaTakatoshi, ItoKensaku, ToyozawaRyo, SetoTakashi, YamaguchiMasafumi, OkamotoTatsuro

Effective for NSCLC
Neurocognitive effects

This case report describes a patient with lung adenocarcinoma harboring a METex14del mutation who experienced a dramatic intracranial response to tepotinib, a MET inhibitor. The patient's symptoms from multiple brain metastases rapidly disappeared, suggesting tepotinib's potential as a treatment option for NSCLC patients with symptomatic multiple BMs harboring METex14del.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

7.

A novel c-Met/TRK inhibitor 1D228 efficiently inhibits tumor growth by targeting angiogenesis and tumor cell proliferation.

Author: AnBaijiao, NieWenyan, HuJinhui, FanYangyang, NieHaoran, WangMengxuan, ZhaoYaxuan, YaoHan, RenYuanyuan, ZhangChuanchuan, WeiMengna, LiWei, LiuJiadai, YangChunhua, ZhangYin, LiXingshu, TianGeng

Anti-tumor activity
Lower toxicity
Stronger antitumor activity

This study developed a new tyrosine kinase inhibitor, 1D228, that targets both c-Met and TRK, two proteins that promote tumor growth. 1D228 showed better anti-tumor activity in laboratory and animal studies than other drugs that target these proteins. The study suggests that 1D228 may be a promising new treatment for cancer patients with abnormal expressions of c-Met or NTRK.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

8.

Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice.

Author: LeXiuning, SakaiHiroshi, FelipEnriqueta, VeillonRemi, GarassinoMarina Chiara, RaskinJo, CortotAlexis B, ViteriSantiago, MazieresJulien, SmitEgbert F, ThomasMichael, IamsWade T, ChoByoung Chul, KimHye Ryun, YangJames Chih-Hsin, ChenYuh-Min, PatelJyoti D, BestvinaChristine M, ParkKeunchil, GriesingerFrank, JohnsonMelissa, GottfriedMaya, BritschgiChristian, HeymachJohn, SikogluElif, BerghoffKarin, SchumacherKarl-Maria, BrunsRolf, OttoGordon, PaikPaul K

Durable clinical activity
Intracranial disease control
Grade 3 TRAEs

Tepotinib showed meaningful activity in subgroups of patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC) by age, prior therapies, and brain metastases, with a manageable safety profile and few treatment discontinuations.

Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Randomized Trial of Tepotinib Plus Gefitinib versus Chemotherapy in EGFR-Mutant NSCLC with EGFR Inhibitor Resistance Due to MET Amplification: INSIGHT Final Analysis.

Author: LiamChong Kin, AhmadAzura Rozila, HsiaTe-Chun, ZhouJianying, KimDong-Wan, SooRoss Andrew, ChengYing, LuShun, ShinSang Won, YangJames Chih-Hsin, ZhangYiping, ZhaoJun, BerghoffKarin, BrunsRolf, JohneAndreas, WuYi-Long

Improved OS
Improved PFS

Tepotinib plus gefitinib demonstrated improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy in patients with MET-amplified EGFR-mutant non-small cell lung cancer (NSCLC) who had progressed on EGFR inhibitors. In a subgroup analysis of 19 patients, median PFS was 4.9 months vs 4.4 months and median OS was 19.9 months vs 2.8 months for tepotinib plus gefitinib vs chemotherapy, respectively. These results suggest tepotinib plus gefitinib as a promising therapeutic option for this specific patient population.

Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

MET-targeted therapies for the treatment of non-small-cell lung cancer: A systematic review and meta-analysis.

Author: XuLinrui, WangFaping, LuoFengming

Improved outcomes
Adverse events

MET inhibitors showed a satisfactory safety profile with a pooled objective response rate (ORR) of 28.1% and disease control rate (DCR) of 69.1% in patients with non-small cell lung cancer (NSCLC). Tepotinib and savolitinib exhibited higher ORRs (44.7% and 42.9%) compared to other MET inhibitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

11.

Tepotinib reverses ABCB1-mediated multidrug resistance in cancer cells.

Author: WuZhuo-Xun, TengQiu-Xu, CaiChao-Yun, WangJing-Quan, LeiZi-Ning, YangYuqi, FanYing-Fang, ZhangJian-Ye, LiJun, ChenZhe-Sheng

Overcoming MDR

Tepotinib, a MET tyrosine kinase inhibitor with anticancer potential, effectively reversed ABCB1-mediated multidrug resistance (MDR) by inhibiting the efflux activity of the ABCB1 transporter. This study suggests that co-administrating tepotinib with other chemotherapeutic agents could overcome MDR and enhance therapeutic efficacy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

12.

Metabolomics reveals tepotinib-related mitochondrial dysfunction in MET-activating mutations-driven models.

Author: PoliakováMichaela, FelserAndrea, PierzchalaKatarzyna, NuofferJean-Marc, AebersoldDaniel Matthias, ZimmerYitzhak, ZamboniNicola, MedováMichaela

Anticancer therapy
MET inhibition

This study investigated the role of MET signaling in conferring a unique metabolic phenotype to cellular models expressing MET-activating mutated variants that are either sensitive or resistant to MET small molecule inhibitors. The study found that MET inhibition by tepotinib significantly altered the metabolic profile of sensitive cells, suggesting that changes in metabolic state could be used as an early indicator of effective MET inhibition.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Randomised Phase 1b/2 trial of tepotinib vs sorafenib in Asian patients with advanced hepatocellular carcinoma with MET overexpression.

Author: RyooBaek-Yeol, ChengAnn-Li, RenZhenggang, KimTae-You, PanHongming, RauKun-Ming, ChoiHye Jin, ParkJoong-Won, KimJee Hyun, YenChia Jui, LimHo Yeong, ZhouDongli, StraubJosef, ScheeleJuergen, BerghoffKarin, QinShukui

Improved PFS
Improved TTP
Improved response
Grade 3 AE

Tepotinib improved time to progression compared to sorafenib and was well tolerated in SACT-naive Asian patients with hepatocellular carcinoma and MET overexpression.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

14.

Phase I trial of the MET inhibitor tepotinib in Japanese patients with solid tumors.

Author: ShitaraKohei, YamazakiKentaro, TsushimaTakahiro, NaitoTateaki, MatsubaraNobuaki, WatanabeMorihiro, SarholzBarbara, JohneAndreas, DoiToshihiko

A Phase I clinical trial in Japanese patients with solid tumors determined the recommended Phase II dose of tepotinib, a selective MET inhibitor, to be 500 mg once daily. This dose was based on safety and tolerability data obtained in the trial.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.

Language : English

15.

Phase 1b/2 trial of tepotinib in sorafenib pretreated advanced hepatocellular carcinoma with MET overexpression.

Author: DecaensThomas, BaroneCarlo, AssenatEric, WermkeMartin, FasoloAngelica, MerlePhilippe, BlancJean-Frédéric, GrandoVéronique, IacobellisAngelo, VillaErica, TrojanJoerg, StraubJosef, BrunsRolf, BerghoffKarin, ScheeleJuergen, RaymondEric, FaivreSandrine

Promising efficacy
Well tolerated
Lipase increase
Peripheral edema

A Phase 1b/2 study of 66 patients with sorafenib pretreated advanced hepatocellular carcinoma (aHCC) with MET overexpression found that tepotinib was generally well tolerated and the recommended Phase 2 dose (RP2D) showed promising efficacy. The 12-week progression-free survival (PFS) was 63.3% in the tepotinib group, which was significantly greater than the predefined null hypothesis of ≤15%.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Emerging MET tyrosine kinase inhibitors for the treatment of non-small cell lung cancer.

Author: FujinoToshio, SudaKenichi, MitsudomiTetsuya

Treat activated MET

This review discusses the importance of MET aberrations in non-small cell lung cancer (NSCLC) and the development of MET-TKIs as targeted therapies. While promising results have been observed, inherent and acquired resistance to MET-TKIs remain challenges.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

18.

Real-World Treatment Outcomes of MET Exon14 Skipping in Non-small Cell Lung Cancer: GFPC 03-18 Study.

Author: BabeyHélène, JammePhilippe, CurcioHubert, AssiéJean Baptiste, VeillonRemi, DoubreHélène, PérolMaurice, GuisierFlorian, HuchotEric, DecroisetteChantal, FalcheroLionel, CorreRomain, CortotAlexis, ChouaïdChristos, DescourtRenaud

No benefit with anti-MET TKIs

A retrospective study of 118 patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping mutations (METexon14) found no evidence of a benefit in overall survival (mOS) with anti-MET tyrosine kinase inhibitors (TKIs). The mOS was 27.1 months (95% CI 18-31.4) with a median follow-up of 16 months (95% CI 13.6-29.7).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

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