Jax DiEugenio

For patients with MET exon 14-altered NSCLC, Tepmetko was associated with frequent side effects, although the safety profile is considered manageable.

Among patients with MET exon 14-altered non-small cell lung cancer (NSCLC), treatment with Tepmetko (tepotinib) was associated with a high frequency of side effects, although the safety profile is considered manageable, according to a pooled safety analysis of cohorts A and C of the phase 2 VISION trial.

Notably, these findings were consistent with prior reports from the trial. In the pooled safety analysis of cohorts A and C (313 patients), any-grade side effects occurred in 99% of patients, and grade 3 (severe) or higher side effects were reported in 68.4% of patients. Treatment-related side effects were observed in 91.7% of patients, including grade 3 or higher in 36.1% of patients. Any-grade serious side effects and serious treatment-related side effects occurred in 54.6% and 16% of patients, respectively. Side effects led to dose reductions in 33.2%, treatment interruptions in 43.8% and permanent discontinuation in 15.7% of patients. These rates of treatment-related side effects were 33.2%, 43.8% and 15.7%, respectively. Additionally, 13.7% of patients experienced a side effect that led to death, three of which were treatment related.

The most common treatment-related side effects included peripheral edema (any-grade, 67.7%; grade 3 or higher, 11.8%), hypoalbuminemia (25.2%; 3.8%), nausea (23.3%; 0.6%), diarrhea (22.7%; 0.3%), increased blood creatinine levels (22.0%; 1.3%), alanine aminotransferase (ALT) level elevation (14.1%; 2.2%), decreased appetite (11.5%; 0.3%), aspartate aminotransferase level elevation (11.2%; 1.9%) and amylase level increase (10.5%; 1.9%).

Peripheral edema: swelling of the extremities.

Hypoalbuminemia: low levels of albumin in the blood.

Alanine aminotransferase (ALT) level elevation: an indication of liver damage.

Aspartate aminotransferase level elevation: an indication of liver or muscle damage.

Pleural effusion: accumulation of fluid between the lungs and the chest wall.

ECOG performance status: a method of measuring patients’ ability to complete daily tasks, with lower scores indicating greater independence.

In total, 37.4% of patients required at least one dose reduction. The most common any-grade treatment-related side effect leading to dose reduction, treatment interruption and treatment discontinuation was peripheral edema (15.3%, 18.8%, and 6.1% of patients, respectively). Other treatment-related side effects leading to dose reductions were generalized edema (3.2%), edema (2.2%), pleural effusion (1.6%), increased blood creatinine levels (2.6%), hypoalbuminemia (1.3%), fatigue (1.0%), asthenia (1.0%) and localized edema (1.0%). Other treatment-related side effects leading to treatment interruptions included increased blood creatinine levels (5.8%), generalized edema (4.8%), edema (3.5%), pleural effusion (3.2%), increased ALT levels (2.6%), localized edema (2.2%) and nausea (2.2%). Other treatment-related side effects leading to treatment discontinuation included edema (1.3%), generalized edema (1.0%), pleural effusion (1.0%), interstitial lung disease (1.0%) and pneumonitis (1.0%).

Additionally, health-related quality of life (HRQOL) patient-reported outcome (PRO) scores remained stable with Tepmetko use. Investigators observed no meaningful change in European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) or EuroQol 5-Dimension 5-Level (EQ-5D-5L) scores up to 228 weeks. At the end of treatment, among patients evaluated for HRQOL, the mean change from baseline for the EORTC QLQ-C30 global health status (GHS) was –7.1 and the mean change for the EuroQol visual analogue scales (EQ-VAS) was –10; positive values signified improvement. The mean changes from baseline in the EORTC QLQ-lung cancer (LC13) symptom scores for cough, dyspnea and chest pain, respectively, were –6.1, 7.1 and –2.3; negative values signified improvement. Furthermore, the median time to deterioration of the EORTC QLQ-LC13 symptom scores for cough, chest pain, and dyspnea were 36.5 months, 30.4 months and 5.5 months, respectively.

“Throughout the VISION trial, patients completed questionnaires evaluating their QOL before and while receiving [Tepmetko],” Dr. Enriqueta Felip, lead study author and head of the Thoracic Cancer Unit at Hospital Universitari de la Vall d'Hebron in Barcelona, Spain, and coauthors explained in the conclusion of the poster presentation. “Overall, patients reported that health and QOL remained stable while receiving [Tepmetko]. Specific scores relating to symptoms experienced by patients with lung cancer were improved during treatment for symptoms such as cough and chest pain and remained stable for shortness of breath.”

What Was the Design of the VISION Trial of Tepmetko in Patients With 

The VISION trial was a single-arm study evaluating Tepmetko in patients with advanced NSCLC harboring MET exon 14 skipping alterations.The study evaluated Tepmetko at a dose of 500 mg orally once daily and comprised three cohorts.

Eligible patients were at least 18 years of age, had histologically or cytologically confirmed NSCLC with MET exon 14 skipping alterations detected by liquid biopsy and/or tissue biopsy, measurable disease and an ECOG performance status of 0 or 1. Prior immunotherapy was permitted.

Patients were excluded if their tumors harbored EGFR mutations or ALK rearrangements, if they had received more than two prior lines of systemic therapy, or if they had prior exposure to MET or HGF inhibitors.

What Were the Baseline Patient Demographics in the VISION NSCLC Trial?

The median age of patients with MET exon 14 skipping NSCLC was 72 years. In total, 50.8% of patients were female, 73.8% of patients had an ECOG performance status of 1 and 47.6% of patients had received prior treatment.

At study entry, 47.6% of patients had received at least one prior systemic therapy. The median treatment duration was 7.5 months and 19 patients remained on Tepmetko for at least 48 months.

Felip E, Ferrara R, Veillon R, et al. Safety and patient-reported outcomes with tepotinib in patients with 

ex14 skipping NSCLC: ≥3 years follow-up of VISION. Presented at: 2025 IASLC World Conference on Lung Cancer; September 6-10, 2025; Barcelona, Spain. Poster P3.12.40.

Tepotinib phase II in NSCLC harboring MET alterations (VISION). ClinicalTrials.gov. Updated August 14, 2025. Accessed September 9, 2025. https://www.clinicaltrials.gov/study/NCT02864992

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Tepmetko (tepotinib) treatment in MET exon 14-altered NSCLC patients showed a high incidence of side effects, with 99% experiencing any-grade side effects and 68.4% facing severe ones. Treatment-related side effects were common, leading to dose reductions, interruptions, or discontinuations. Despite these, health-related quality of life scores remained stable, with some symptom improvements. The VISION trial, a single-arm study, evaluated Tepmetko in patients with advanced NSCLC, excluding those with EGFR mutations or ALK rearrangements. The median patient age was 72, with a median treatment duration of 7.5 months.

Tepmetko Associated With Frequent Side Effects for Some With NSCLC

People with EGFR+ NSCLC whose disease spread outside the brain after treatment with Tagrisso lived longer when they kept taking Tagrisso along with chemo: © stock.adobe.com

People with EGFR-positive non–small cell lung cancer (NSCLC) whose disease spread outside the brain after treatment with Tagrisso lived longer when they kept taking Tagrisso along with chemotherapy, according to a phase 3 study shared at the 2025 World Conference on Lung Cancer.

The data, which were shared in a press briefing, indicated that the combination of Tagrisso and chemotherapy (49 patients) was linked with improved progression-free survival versus placebo plus chemotherapy (49 patients). The median progression-free survival in the respective arms was 8.4 months and 4.4 months. The data were at 76% maturity and the median follow-up in the Tagrisso and placebo arms was 5.4 months and 5.5 months, respectively.

In evaluable patients without baseline central nervous system metastases, the central nervous system progression-free survival with Tagrisso plus chemotherapy (38 patients) was longer, at 15.9 months, versus 8.6 months with placebo plus chemotherapy (37 patients). These data were at 43% maturity, and the median follow-up was 5.5 months and 5.6 months in the respective arms. Moreover, the Tagrisso combination was also linked with improved non–central nervous system progression-free survival versus chemotherapy alone. The median non–central nervous system progression-free survival in the respective arms was 8.4 months and 5.2 months. Data maturity was 73%, and the median follow-up was 3.6 months in both arms.

Moreover, with data at 55% maturity, the median overall survival was longer with Tagrisso plus chemotherapy versus placebo plus chemotherapy, at 15.9 months and 9.8 months, respectively. The median follow-up in the respective arms was 12 months and 11.1 months.

“These results indicate that resistance to first-line Tagrisso may be heterogeneous, and some tumor cells remain sensitive to continued therapy,” Giulia Pasello, MD, PhD, of the Veneto Institute of Oncology IOV-IRCCS and the University of Padova in Padova, Italy, said in a news release. “This trial supports Tagrisso as a backbone treatment strategy in this setting.”

In the Realm of EGFR-Mutated Non–Small Cell Lung Cancer, What Did the Phase 3 Study Examine?

The global, randomized, double-blind, phase 3 study enrolled patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer with or without central nervous system metastases. These patients were at least 18 years of age, experienced non–central nervous system progression on first-line Tagrisso, and had a World Health Organization performance score of 0 or 1; their EGFR mutations were exon 19 deletion or L858R.

Study participants (98 patients) were randomized 1:1 to receive placebo or 80 mg of Tagrisso once daily plus 75 mg/m2 of cisplatin or area under the curve 5 of carboplatin plus 500 mg/m2 of pemetrexed given every 3 weeks for 4 cycles followed by placebo or 80 mg of Tagrisso once daily plus 500 mg/m2 of pemetrexed every 3 weeks. Treatment continued until progressive disease or other discontinuation criteria were met. Patients were stratified by the presence of central nervous system metastases (yes versus no).

Imaging assessments of the chest and abdomen and the brain were done at baseline and every 6 weeks for the first 13 cycles; they were done every 12 weeks thereafter. The primary end point of the study was investigator-assessed progression-free survival, and key secondary end points comprised central nervous system progression-free survival according to baseline central nervous system metastases status, non–central nervous system progression-free survival, and overall survival.

A total of 98 patients were randomized, and 96 patients were dosed; 48 patients were randomized to the Tagrisso arm and 48 were randomized to the placebo arm; 15% and 8% of patients were still receiving Tagrisso or placebo at the time of data cutoff, which was October 28, 2024; 13% and 8% of patients in the respective arms were still receiving pemetrexed.

Across the Tagrisso and placebo arms, the median patient age was 62 years. Most patients were female (61%; 80%), never smokers (65%; 67%), and White (80%; 78%), and about half had an ECOG performance status of 1 (53%; 51%). Most patients had stage 4 disease by American Joint Committee on Cancer criteria at the time of study entry (100%; 98%). Central nervous system metastases were present in 22% of those in the Tagrisso arm versus 24% of those in the placebo arm. The more common EGFR mutation type was exon 19 deletions (65%; 55%). The median time on first-line Tagrisso in the respective arms was 21.3 months and 19.6 months.

What Else Is Known About the Efficacy of Tagrisso Plus Chemotherapy in this Setting?

The 6-month progression-free survival rate with Tagrisso plus chemotherapy was 64% versus 32% with placebo plus chemotherapy. The 6-month central nervous system progression-free survival rates were 87% and 63% in the respective arms, and the 6-month non–central nervous system progression-free survival rates were 65% and 35%, respectively. The 6-month overall survival rates were 67% and 47%.

The non–central nervous system objective response rate in the Tagrisso arm (49 patients) was 35% versus 29% in the placebo arm (49 patients). The median non–central nervous system duration of response was 8.2 months with Tagrisso versus 4.2 months without.

New lesions were reported in 37% of those in the Tagrisso arm versus 51% of those on the placebo arm, with fewer patients in the Tagrisso arm experiencing new brain lesions (10% versus 27%).

What is the Side Effect Profile of Tagrisso Plus Chemotherapy?

Safety data for the Tagrisso combination aligned with what has previously been reported for each drug. Any-grade side effects occurred in 98% of those in the Tagrisso and placebo arms; 63% and 46% of them were grade 3 or higher. Serious side effects were experienced by 38% and 31% of patients in the respective arms, and side effects proved fatal for 1 patient in each arm. Side effects led to discontinuation of Tagrisso or placebo, pemetrexed, or platinum for 13%, 19%, and 13% of patients in the Tagrisso arm; these respective rates were 2%, 2%, and 0% in the placebo arm.

The most common grade 3 side effects in the Tagrisso and placebo arms were anemia (13%; 13%), neutropenia (13%; 2%), decreased white blood cell count (10%; 4%), decreased neutrophil count (8%; 6%), decreased platelet count (6%; 2%), increased aspartate aminotransferase levels (4%; 0%), nausea (2%; 0%), increased alanine aminotransferase levels (2%; 2%), and decreased appetite (2%; 0%). The most common grade 4 events in the Tagrisso arm were neutropenia, increased alanine aminotransferase levels, decreased neutrophil count, and decreased white blood cell count (2% each). In the placebo arm, these were decreased platelet count (4%) and neutropenia (2%).

Pasello G, Zhao J, Tufman A, et al. COMPEL: Osimertinib + platinum-based chemotherapy in patients with EGFRm advanced NSCLC and progression on 1L osimertinib. Presented at: 2025 International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Abstract 1174.

COMPEL study shows continuing osimertinib treatment through progression with the addition of chemotherapy improves progression-free survival in EGFR-mutated NSCLC. News release. International Association for the Study of Lung Cancer 2025 World Conference on Lung Cancer. September 6, 2025. Accessed September 6, 2025. https://wclc.iaslc.org/

A study to evaluate chemotherapy plus osimertinib against chemotherapy plus placebo in patients with non-small cell lung cancer (NSCLC) (COMPEL). ClinicalTrials.gov. Updated July 10, 2025. Accessed September 6, 2025. https://clinicaltrials.gov/study/NCT04765059

For more news on cancer updates, research and education, 

A phase 3 study demonstrated that patients with EGFR-positive non-small cell lung cancer (NSCLC) who continued Tagrisso alongside chemotherapy after disease progression outside the brain experienced longer progression-free survival compared to those on placebo plus chemotherapy. The study highlighted significant improvements in both central nervous system and non-central nervous system progression-free survival, as well as overall survival, with the Tagrisso combination. Safety profiles were consistent with known data, with common side effects including anemia and neutropenia. The findings support Tagrisso as a foundational treatment strategy in this context.

People with EGFR+ NSCLC whose disease spread outside the brain after treatment with Tagrisso lived longer when they kept taking Tagrisso along with chemo.

Tagrisso With Chemotherapy Improves Survival in EGFR+ NSCLC

Iza-bren and Tagrisso showed beneficial results as an initial treatment for advanced/metastatic EGFR-mutated NSCLC: © stock.adobe.com.

A combination of Iza-bren (izalontamab brengitecan; BL-B01D1) and Tagrisso showed beneficial results as an initial treatment for people with advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR mutations. The treatment was generally well tolerated and helped shrink tumors, according to results from a phase 2 study shared at the 2025 World Conference on Lung Cancer.

Notably, when Iza-bren was given at a dose of 2.5 milligrams per kilogram (mg/kg) on days one and eight of an every-three-weeks cycle and combined with Tagrisso (40 patients), it led to an objective response rate of 100% and a confirmed objective response rate of 95%. At a median follow-up of 12.5 months, the 12-month progression-free survival rate was 92%. At a median follow-up of 12.8 months, the 12-month overall survival rate was 95%. The median duration of response and median progression-free survival had not yet been reached at the time of analysis, which had a data cutoff date of June 30, 2025.

When the first-in-class bispecific antibody-drug conjugate was given at doses combined with Tagrisso, the first-line regimen was found to be tolerable with a manageable side effect profile. The most common treatment-related side effects were hematologic, and a low incidence of side effects led to treatment discontinuation.

“These results are remarkable and suggest that this combination could offer a potentially transformative first-line treatment option for EGFR-mutant NSCLC,” Dr. Fei Zhou, presenting author from Shanghai East Hospital, stated in a news release spotlighting the data. “Importantly, the regimen was also manageable from a safety perspective.”

What Is the Design of the Phase 2 Study Examining Iza-bren Plus Tagrisso in NSCLC?

The phase 2 trial enrolled treatment-naive patients with locally advanced or metastatic NSCLC harboring EGFR-sensitizing mutations. Patients had an ECOG performance status of zero or one and measurable disease by RECIST criteria.

Patients received Iza-bren at doses of 2.2 mg/kg (41 patients), 2.5 mg/kg (40 patients), and 2.75 mg/kg (42 patients) on days one and eight of every three-week cycles and 4 mg/kg (18 patients) and 4.5 mg/kg (13 patients) on day one of every three-week cycles in combination with 80 mg of Tagrisso given once daily. The primary end points were objective response rate and to identify the recommended phase 2 dose of Iza-bren. Secondary end points included progression-free survival, disease control rate, duration of response, and safety. Exploratory end points comprised pharmacokinetics, neutralizing antibody, drug-drug interactions, overall survival, and biomarker analysis.

A total of 154 patients received the regimen spanning doses. At the time of data cutoff, 111 patients were still receiving treatment and 43 had discontinued. The most common reasons for discontinuation were progressive disease (14 patients), followed by side effects (7 patients) and death (2 patients). All patients were included in the safety and efficacy analysis sets. The median patient age was 60 years, and just under half were male (43.5%). More than half were never smokers (60.4%), and most had an ECOG performance status of 1 (80.5%). The median number of metastatic organs was three, and 27.3% of patients had baseline brain metastases. Moreover, 57.8% and 42.2% of patients had EGFR exon 19 deletion mutations or EGFR L858R mutations, respectively.

What Was the Preliminary Efficacy of Iza-bren Plus Tagrisso?

In the total population, the regimen induced an objective response rate of 84.4%; the confirmed objective response rate was 80.5%. At a median follow-up of 12.7 months and 15 months for progression-free survival and overall survival, respectively, the 12-month rates were 86.5% and 95.9%.

In those who received Iza-bren at a dose of 2.2 mg/kg on days 1 and 8 of every 3-week cycles, the objective response rate was 78% and the confirmed objective response rate was 73.2%. In those who received the antibody-drug conjugate at a dose of 2.75 mg/kg on days one and eight of every three-week cycles, the objective response rate was 78.6% and the confirmed objective response rate was 76.2%. In those given Iza-bren at 4 mg/kg on day one of every three-week cycles, the objective response rate and confirmed objective response rate were both 77.8%. In the group of patients who received Iza-bren at a dose of 4.5 mg/kg on day one of every three-week cycles, the objective response rate was 84.6% and the confirmed objective response rate was 76.9%.

Of the patients who received Iza-bren at doses given on the day one and eight schedule (123 patients), 95.9% experienced tumor shrinkage; the median shrinkage percentage was –53.8%. All patients who received Iza-bren at a dose of 2.5 mg/kg on this schedule experienced tumor shrinkage; the median shrinkage percentage was –56.7%.

What Was the Safety Profile of Iza-bren Plus Tagrisso?

The majority of side effects were hematologic, with high incidences of anemia (91.9%), neutropenia (91.1%), leukopenia (91.1%), and thrombocytopenia (75.6%). Non-hematologic side effects included nausea, stomatitis, decreased appetite, vomiting, diarrhea, asthenia, elevated aspartate aminotransferase and alanine aminotransferase levels, hypokalemia, hypoalbuminemia, weight loss, rash, and alopecia.

Grade 3 or higher side effects were manageable with supportive measures, including dose reductions and growth factor support. The discontinuation rate of Iza-bren due to side effects was 13%, and no new safety signals were identified. Zhou noted that there were 2 cases of interstitial lung disease reported; one case was grade 2 and the other was grade 3.

A phase 3 clinical trial is further evaluating Iza-bren at 2.5 mg/kg on days one and eight of every three-week cycles in combination with Tagrisso as a first-line treatment for patients with EGFR-mutated NSCLC. This trial is currently being conducted in China and is designed to confirm the efficacy and safety of the combination in a larger, randomized population.

“Phase II study of iza-bren (BL-B01D1) in combination with osimertinib in patients with EGFR-mutated locally advanced or metastatic non–small cell lung cancer,” by Dr. Fei Zhou, et al. by. Presented at: IASLC 2025 World Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain. Press Briefing. Abstract 2114.

Iza-bren in combination with osimertinib shows 100% response rate in EGFR-mutated NSCLC, phase II study finds,” by WCLC. News Release. September 6, 2025. https://wclc.iaslc.org/

The combination of Iza-bren and Tagrisso demonstrated promising results as a first-line treatment for advanced or metastatic NSCLC with EGFR mutations. The phase 2 study reported a 100% objective response rate and a 95% confirmed response rate at a 2.5 mg/kg dose of Iza-bren. The 12-month progression-free survival and overall survival rates were 92% and 95%, respectively. The regimen was well tolerated, with manageable hematologic side effects. A phase 3 trial is underway to further evaluate the combination's efficacy and safety in a larger population.

A combination of Iza-bren and Tagrisso showed beneficial results as an initial treatment for advanced/metastatic EGFR-mutated non–small cell lung cancer. 

Iza-bren Plus Tagrisso May Offer a New Option for Advanced Lung Cancer 

Never-smoker Leah Phillips, co-founder of the Young Lung Cancer Initiative, raises awareness that anyone with lungs can develop lung cancer. 

Dispelling Myths and Raising Awareness of Lung Cancer Risk 

Leah Phillips, co-founder of the Young Lung Cancer Initiative, had her life profoundly altered when she was diagnosed with stage IV lung cancer driven by an EGFR exon 19 mutation. A never-smoker, Leah had no traditional risk factors and initially believed her diagnosis must have been a mistake. This experience has fueled her advocacy, as she seeks to dispel the misconception that lung cancer only affects smokers or older adults.

“If you have lungs, you can develop lung cancer,” she emphasized in an interview with CURE during the 2025 IASCLC World Conference on Lung Cancer (WCLC).

During the interview, Leah discusses the importance of awareness, encouraging both the public and medical community to recognize persistent symptoms that may signal an underlying condition requiring further evaluation 

As a never-smoker, what do you wish more people understood about who can be affected by lung cancer?

Honestly, people need to realize that if you have lungs, you can get lung cancer. When I was diagnosed, I was living in Kentucky, a tobacco state where I am from. My grandparents smoked from the time they were 12. That's just because they were tobacco farmers, and that's what they did. It was such a normal thing in our society. My parents did not smoke, and I never smoked, but everybody I knew who ever had lung cancer had been a smoker and was older.

When I was first diagnosed, and they knew it was malignant cancer, they were trying to figure out where it was coming from. When it came back as lung cancer, I thought they were in the wrong room because they had led me to believe it was going to be breast, colon, or ovarian cancer given my health status, my age, and so on.

I think that is my big mission: letting others know that you can get lung cancer even if you don't have risk factors. In my prior life as a teacher, I wasn't working around harsh chemicals, and we don't live in an old home. It was just really surreal to get that information and process how this could happen.

That's the biggest point and what's been my driving force: to let not only people with lung cancer know this, but also researchers, doctors, and people at large by sharing my story. This way, they can relate and be like, “Oh, so if I have a nagging cough or if I have wheezing, I shouldn't just take it for granted that it's a little cold.”

Transcript has been edited for clarity and conciseness.

Jax DiEugenio

Tepmetko Associated With Frequent Side Effects for Some With NSCLC

Tagrisso With Chemotherapy Improves Survival in EGFR+ NSCLC

Iza-bren Plus Tagrisso May Offer a New Option for Advanced Lung Cancer

Dispelling Myths and Raising Awareness of Lung Cancer Risk

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