---
title: "Zipalertinib (CLN-081) in EGFR exon 20 insertion-mutated non-small-cell lung cancer: cost-effectiveness analyses and utility weights"
description: "Published cost-effectiveness analyses and health-state utility weights for Zipalertinib (CLN-081, TAS6417) in EGFR exon 20 insertion-mutated non-small-cell lung cancer, each value quoted from the article: 9 cost-effectiveness analyses and 6 studies reporting utility weights. Analyses: Amivantamab plus carboplatin-pemetrexed versus carboplatin-pemetrexed in first-line NSCLC with EGFR exon 20 insertions, United States: Yue et al. (2024); Amivantamab plus chemotherapy versus chemotherapy in NSCLC with EGFR exon 20 insertions, United States: Cao et al. (2024); Amivantamab plus lazertinib versus osimertinib in previously untreated EGFR-mutated advanced NSCLC, United States and China: Wu et al. (2025); Amivantamab plus lazertinib and lazertinib versus osimertinib in EGFR-mutated advanced NSCLC, China: Zhang et al. (2025); 5 further articles. Utility weights: Utility weights for progression-free and progressed disease and adverse events, NSCLC with EGFR exon 20 insertions: Yue et al. (2024); Utility weights for progression-free and progressed disease and EGFR inhibitor adverse events, EGFR-mutated advanced NSCLC: Zhang et al. (2025); Utility weights for progression-free and progressive disease in the United States and China, EGFR-mutated advanced NSCLC: Wu et al. (2025); Utility weights for progression-free and progressive disease on EGFR TKI, chemotherapy or immunotherapy, and best supportive care, EGFR-mutant advanced NSCLC: Ezeife et al. (2018); 2 further articles. Every value is a verbatim quote from the primary article it is shown with."
canonical: "https://www.evicenter.com/drugs/zipalertinib--egfr-exon-20-insertion-mutated-non-small-cell-lung-cancer/cost-effectiveness-analyses"
published: "2026-10-22T07:49:06-04:00"
modified: "2026-10-22T07:49:06-04:00"
---
# Zipalertinib (CLN-081) in EGFR exon 20 insertion-mutated non-small-cell lung cancer: cost-effectiveness analyses and utility weights
Published cost-effectiveness analyses and health-state utility weights that a model of this product could cite, adapt, or compare against, grouped by how each article relates to the product and its indication. Every value is quoted from the article it cites, and section 3 lists the searches that found the articles.
## Overview
| Item | Detail |
| --- | --- |
| Literature searched | Tufts Medical Center Cost-Effectiveness Analysis Registry, searched October 21, 2026; the queries are listed in section 3. |
| Cost-effectiveness analyses | 9 |
| Studies reporting utility weights | 6 |
## 1 Cost-effectiveness analyses
### 1.1 Analyses of Zipalertinib (CLN-081 and TAS6417)
No evidence found.
### 1.2 Treatments for the same indication
#### Amivantamab plus carboplatin-pemetrexed versus carboplatin-pemetrexed in first-line NSCLC with EGFR exon 20 insertions, United States: Yue et al. (2024)
Relevance: Evaluates first-line amivantamab plus carboplatin-pemetrexed against carboplatin-pemetrexed in EGFR exon 20 insertion non-small-cell lung cancer in the United States; amivantamab plus chemotherapy is the first-line standard of care listed in section 2, and chemotherapy alone is the control arm of REZILIENT3.
> “We constructed a Markov model based on the data derived from the PAPILLON trial.”
> “The simulation cycle duration was 3 weeks, which was consistent with the PAPILLON trial.”
> “In this study, a 3% annual discount rate was applied for future health utility and cost”
> “The baseline findings revealed that amivantamab–chemotherapy resulted in 1.904 QALYs (2.973 LYs), whereas chemotherapy alone generated 1.423 QALYs (2.161 LYs).”
> “The cost of amivantamab–chemotherapy was $430,980.857, while the cost of chemotherapy alone was $62,908.322.”
> “Compared with chemotherapy alone, amivantamab combined with chemotherapy treatment gained an incremental effectiveness of 0.473 QALYs and an incremental cost of $361,950.952, which resulted in an ICER of $765,224/QALY.”
> “The cost-effectiveness acceptability curves showed amivantamab–chemotherapy was not cost-effective at all compared to the WTP threshold”
> “From the perspective of the American healthcare system, the amivantamab combination with chemotherapy was not a cost-effective first-line regimen compared with chemotherapy alone for advanced NSCLC harboring EGFR exon 20 insertions.”
Source: [Yue et al. (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10995216/)
#### Amivantamab plus chemotherapy versus chemotherapy in NSCLC with EGFR exon 20 insertions, United States: Cao et al. (2024)
Relevance: Evaluates amivantamab plus chemotherapy in EGFR exon 20 insertion non-small-cell lung cancer from a United States payer perspective, the comparator model by Cao et al. summarized in section 4.1.
> “To evaluate the cost-effectiveness of amivantamab plus chemotherapy for the treatment of NSCLC patients with EGFR exon 20 insertions from the United States payer perspective.”
> “A partitioned survival model was developed based on the data from the PAPILLON trial.”
> “A 3% annual discount rate was applied to both costs and outcomes.”
> “Amivantamab plus chemotherapy yielded an additional 1.12 quality-adjusted life years (QALYs) while increasing costs by $483,769.50 relative to the chemotherapy regimen, leading to an ICER of $432,401.16/QALY.”
> “The combination of amivantamab with chemotherapy was not cost effective at a threshold of $150,000/QALY.”
> “For PSA, the probability that amivantamab plus chemotherapy would be cost-effective was 0% if the willingness-to-pay (WTP) threshold was $150,000/QALY.”
Source: [Cao et al. (2024)](https://pubmed.ncbi.nlm.nih.gov/38990458/)
### 1.3 The same disease in other populations or settings
#### Amivantamab plus lazertinib versus osimertinib in previously untreated EGFR-mutated advanced NSCLC, United States and China: Wu et al. (2025)
Relevance: Evaluates first-line amivantamab plus lazertinib against osimertinib in previously untreated EGFR-mutated advanced non-small-cell lung cancer in United States and Chinese healthcare settings, based on the MARIPOSA trial, with amivantamab the EGFR-MET bispecific antibody listed in section 2.
Access: Not open access
> “This study evaluates the cost-effectiveness of AL regimen compared with osimertinib in US and Chinese healthcare settings.”
> “A partitioned survival model, comprising progression-free survival (PFS), post-progression, and death states, was developed using a Markov model.”
> “Clinical data were obtained from the recent Phase III MARIPOSA trial.”
> “In the base case analysis, the average costs of AL and osimertinib regimen were $1,030,524.3 (China: $234,270.87) and $466,922.0 (China: $20,075.35), respectively, and the QALYs achieved were 4.08 (China: 3.66) and 2.60 (China: 2.66), respectively.”
> “The ICERs for AL compared with osimertinib in the US and China were $563,602.3 and $214,195.51, respectively.”
> “Based on the respective WTP thresholds in the US and China, the AL regimen did not represent a cost-effective option.”
Source: [Wu et al. (2025)](https://pubmed.ncbi.nlm.nih.gov/40220717/)
#### Amivantamab plus lazertinib and lazertinib versus osimertinib in EGFR-mutated advanced NSCLC, China: Zhang et al. (2025)
Relevance: Evaluates amivantamab plus lazertinib and lazertinib alone against osimertinib in EGFR-mutated non-small-cell lung cancer in China.
> “we constructed a Markov model for 3-week cycles over a 5-year horizon.”
> “The primary outcomes of the model included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER), where all economic parameters were discounted at 3.0% annually.”
> “From the perspective of the healthcare system, our research focused only on the direct medical costs, including the costs of the drugs, AE management, and monitoring.”
> “The cost-utility analyses employed China’s per capita gross domestic product for 2023 (ranging from $12,295.7 to $36,887.0) as the willingness-to-pay (WTP) threshold”
> “The economic evaluations demonstrated that compared to osimertinib monotherapy, the amivantamab–lazertinib combination yielded an additional 1.11 QALYs at an incremental cost of $1,342,374, producing an ICER of $1,211,236/QALY that substantially exceeds the $36,887 WTP threshold.”
> “Similarly, lazertinib monotherapy showed a QALY gain of 0.71 with $224,248 of additional costs (ICER = $315,640/QALY), also surpassing the lower threshold of $12,296.”
Source: [Zhang et al. (2025)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12081244/)
#### Osimertinib versus platinum-pemetrexed in previously treated EGFR T790M-positive advanced NSCLC, United States and China: Shi et al. (2022)
Relevance: Evaluates second-line osimertinib against platinum-pemetrexed in previously treated EGFR T790M-positive advanced non-small-cell lung cancer from the perspectives of the United States payer and the Chinese health care system.
> “Here, we assessed the cost-effectiveness of second-line osimertinib versus platinum-pemetrexed, from the perspectives of the United States payer and the Chinese health care system.”
> “A three health states Markov model was established by TreeAge Pro 2021 (TreeAge Software, Williamstown, MA, USA)”
> “The time horizon is the lifetime.”
> “This study applied half-cycle correction and an annual discount rate of 3% and 5% in costs as well as health utilities in the United States and Chinese contexts, respectively”
> “In the United States, compared with platinum-pemetrexed, osimertinib yielded additional effectiveness of 0.43 QALYs and -0.12 QALYs, with incremental costs of $67,588 and $16,465 in the ITT population and CNS metastases population, respectively.”
> “The ICERs of osimertinib over platinum-pemetrexed were $159,126/QALY and $-130,830/QALY, respectively.”
> “The probability of osimertinib being cost-effective was 37% and 5.76%, respectively, at the willingness-to-pay (WTP) threshold of $150,000/QALY.”
> “In China, osimertinib showed incremental effectiveness of 0.34 QALYs and -0.14 QALYs, with incremental costs of $1,663 and $-505, resulting in ICERs of $4,950/QALY and $3,754/QALY in the ITT population and CNS metastases population, respectively.”
> “At the WTP threshold of $37,489/QALY, there was a 100% and 26% likelihood that osimertinib was cost-effective in the ITT population and CNS metastases population.”
Source: [Shi et al. (2022)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9619214/)
#### First-line or second-line osimertinib versus first-generation EGFR TKI followed by chemotherapy in newly diagnosed EGFR-mutated advanced NSCLC, United States and China: Wu et al. (2019)
Relevance: Compares first-line osimertinib, a first-generation EGFR tyrosine kinase inhibitor followed by second-line osimertinib, and first-generation EGFR tyrosine kinase inhibitor therapy alone in newly diagnosed EGFR-mutated advanced non-small-cell lung cancer from public payer perspectives in the United States and China.
> “The objective of this study was to assess cost and effectiveness of osimertinib in treating newly diagnosed advanced non‐small cell lung cancer with an epidermal growth factor receptor (EGFR) mutation from a public payer's perspective in the U.S. and China.”
> “Markov models were developed to compare three treatment strategies: first‐line use of osimertinib, first‐line use of the standard first‐generation EGFR‐tyrosine kinase inhibitor (EGFR‐TKI) followed by the second‐line use of osimertinib, and the standard first‐generation EGFR‐TKI therapy (standard care [SOC]).”
> “Therefore, we used a 10‐year time horizon in the base‐case analysis and varied the time horizon from 1 to 20 years in the sensitivity analyses.”
> “In the base‐case analysis, both costs and QALYs were discounted 3% and 5% annually in the U.S. [33] and China [34], respectively.”
> “For the whole population in the U.S., the mean costs and QALYs associated with the first‐line osimertinib, second‐line osimertinib, and SOC strategies were $511,415 and 2.316, $330,602 and 1.766, and $244,837 and 1.465, respectively.”
> “The corresponding numbers in China were $72,615 and 2.244, $51,658 and 1.757, and $41,159 and 1.487”
> “The resultant ICERs for first‐line osimertinib versus SOC were $312,903 in the U.S. and $41,512 in China.”
> “The ICERs for second‐line osimertinib versus SOC were $284,532 in the U.S. and $38,860 in China.”
> “The probability of the SOC strategy being cost‐effective is 1.0 if the willingness to pay threshold is below $150,000/QALY in the U.S. and below $30,000/QALY in China.”
Source: [Wu et al. (2019)](https://pmc.ncbi.nlm.nih.gov/articles/PMC6519771/)
### 1.4 Related diseases and analogous treatments
#### First-line or second-line pralsetinib versus pemetrexed-cisplatin chemotherapy in RET fusion-positive advanced NSCLC, United States: Liu et al. (2023)
Relevance: Evaluates first-line and second-line pralsetinib against cisplatin plus pemetrexed with pemetrexed maintenance in RET fusion-positive advanced non-small-cell lung cancer in the United States, the first-line and post-platinum settings that REZILIENT3 and REZILIENT1 study for zipalertinib.
> “A Markov model was developed to evaluate the 3 above mentioned PRL-based treatment strategies.”
> “The chemotherapy regimen consisted of cisplatin plus pemetrexed followed by maintenance treatment with pemetrexed.”
> “Clinical data from the ARROW trial were incorporated into the model, and costs and utilities values were obtained through previously published literature and public databases, with both being discounted at 3% per year.”
> “Our study employed a 3-week cycle length and incorporated a lifetime horizon to evaluate the costs and efficacy of various therapeutic regimens.”
> “Compared to chemotherapy, the use of PRL in the first-line therapy resulted in an additional 0.07 QALYs at a cost of $133,561, with an ICER of $1,353,849.65 per QALY.”
> “Similarly, when used in the second-line setting, PRL led to an additional 0.09 QALYs at a cost of $92,797, with an ICER of $559,232.70 per QALY.”
> “The ICER value in the first-line or in the second-line therapy strategy was higher than the US willingness-to-pay (WTP) threshold of $150,000 per QALY.”
Source: [Liu et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10579832/)
#### Sotorasib versus docetaxel in previously treated KRAS G12C-mutated NSCLC, China and United States: Zhu et al. (2024)
Relevance: Evaluates sotorasib against docetaxel in previously treated KRAS G12C-mutated non-small-cell lung cancer from Chinese and United States social perspectives, a previously treated setting comparable to the post-platinum population of REZILIENT1.
> “To evaluate the cost-effectiveness of sotorasib versus docetaxel in non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation from the China and United States’social perspective.”
> “A Markov model that included three states (progression-free survival, post-progression survival, and death) was developed.”
> “The results of running the model for 120 cycles were shown in Table 2 .”
> “In China, sotorasib generated 0.44 QAYL with a total cost of $84372.59.”
> “Compared with docetaxel, the ICER value of sotorasib was $102701.84/QALY, which was higher than willingness to pay (WTP), so sotorasib had no economic advantage.”
> “In the US, sotorasib obtained 0.35 QALY more than docetaxel, ICER was $15,976.50/QALY, which was more than 1 WTP but less than 3 WTP, indicating that the increased cost of sotorasib was acceptable.”
> “When the willingness to pay (WTP) exceeds $102,500, the probability of sotorasib having cost effect increases from 0% to 49%.”
Source: [Zhu et al. (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC11211580/)
#### Tepotinib versus capmatinib in metastatic NSCLC with MET exon 14 skipping, United States: Yang et al. (2023)
Relevance: Evaluates tepotinib against capmatinib in metastatic non-small-cell lung cancer with MET exon 14 skipping from the United States Medicare perspective, in frontline and subsequent lines of therapy.
> “From the US Medicare perspective, this study compared the cost-effectiveness of tepotinib and capmatinib for treating metastatic non–small cell lung cancer with tumors harboring mesenchymal–epithelial transition factor gene exon 14 skipping.”
> “A 3-state partitioned survival model assessed outcomes over a lifetime horizon.”
> “A 10-year time horizon was sufficient for nearly all patients to reach the death state.”
> “A monthly model cycle was selected, in alignment with dosing cycles, and a 3% annual discount rate was applied to health and cost outcomes.”
> “In the base case, tepotinib dominated capmatinib in frontline settings (incremental discounted quality-adjusted life-years [QALYs] and costs of 0.2127 and −$47 756, respectively) while realizing an incremental cost-effectiveness ratio of $274 514/QALY in subsequent lines (incremental QALYs and costs of 0.3330 and $91401, respectively).”
> “In a line agnostic context, tepotinib produced an incremental cost-effectiveness ratio of $105 383/QALY (incremental QALYs and costs of 0.2794 and $29 447, respectively).”
> “Tepotinib could be cost-effective versus capmatinib in frontline and line agnostic contexts, considering the range of willingness-to-pay thresholds recommended by the Institute for Clinical and Economic Review ($100 000-$150 000/QALY).”
Source: [Yang et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10424058/)
## 2 Utility weights
### 2.1 Utility weights from analyses of Zipalertinib (CLN-081 and TAS6417)
No evidence found.
### 2.2 Utility weights for the same indication
#### Utility weights for progression-free and progressed disease and adverse events, NSCLC with EGFR exon 20 insertions: Yue et al. (2024)
Relevance: Utilities for progression-free and progressed non-small-cell lung cancer used in the United States model of amivantamab plus chemotherapy in EGFR exon 20 insertion disease.
> “The utilities of PFS and PD in our model were 0.71 and 0.67”
Source: [Yue et al. (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10995216/)
| Health state | Utility |
| --- | --- |
| “Utility of progression-free” | “0.71 0.57-0.85” |
| “Utility of progressed-disease” | “0.67 0.47-0.71” |
| “Disutility of neutropenia” | “0.20 0.16-0.24” |
| “Disutility of paronychia” | “0.1 0.08-0.12” |
| “Disutility of rash” | “0.03 0.02-0.04” |
| “Disutility of anemia” | “0.07 0.06-0.08” |
| “Disutility of leukopenia” | “0.2 0.16-0.24” |
| “Disutility of thrombocytopenia” | “0.11 0.09-0.13” |
| “Disutility of hypokalemia” | “0.03 0.02-0.04” |
| “Disutility of asthenia” | “0.07 0.06-0.08” |
Source: [Yue et al. (2024)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10995216/)
### 2.3 Utility weights for the same disease in other populations or settings
#### Utility weights for progression-free and progressed disease and EGFR inhibitor adverse events, EGFR-mutated advanced NSCLC: Zhang et al. (2025)
Relevance: Utilities for progression-free and progressed metastatic non-small-cell lung cancer and disutilities for EGFR-inhibitor adverse events, including paronychia, rash, and acneiform dermatitis, in EGFR-mutated disease.
> “For the health utility values, the utility for PFS was 0.71 and that for PD was 0.67, where both were derived from the Chinese subgroup data of the global NSCLC patient health preference study conducted by Nafees et al. (2017)”
Source: [Zhang et al. (2025)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12081244/)
| Health state | Utility |
| --- | --- |
| “Progression-free survival” | “0.71 0.57 0.85” |
| “Progressed disease” | “0.67 0.47 0.71” |
| “Paronychia” | “0.040 0.048 0.032” |
| “Rash” | “0.03 0.02 0.04” |
| “Hypoalbuminemia” | “0.03 0.02 0.04” |
| “Dermatitis acneiform” | “0.1 0.08 0.12” |
| “Pulmonary embolism” | “0.2 0.16 0.24” |
Source: [Zhang et al. (2025)](https://pmc.ncbi.nlm.nih.gov/articles/PMC12081244/)
#### Utility weights for progression-free and progressive disease in the United States and China, EGFR-mutated advanced NSCLC: Wu et al. (2025)
Relevance: Utilities for progression-free and progressive EGFR-mutated advanced non-small-cell lung cancer, sourced from the literature, with separate United States and China values.
Access: Not open access
Not quoted: The utility weights are reported in the full text, which this page does not quote.
> “Health-state utilities were sourced from the literature.”
Source: [Wu et al. (2025)](https://pubmed.ncbi.nlm.nih.gov/40220717/)
#### Utility weights for progression-free and progressive disease on EGFR TKI, chemotherapy or immunotherapy, and best supportive care, EGFR-mutant advanced NSCLC: Ezeife et al. (2018)
Relevance: Utilities for progression-free disease on an EGFR-TKI, progressive disease on an EGFR-TKI or on chemotherapy or immunotherapy, and best supportive care in EGFR-mutant advanced non-small-cell lung cancer.
Access: Not open access
Not quoted: The utility weights are reported in the full text, which this page does not quote.
> “A Markov model was developed to project the outcomes and direct medical costs of initial treatment with osimertinib or current standard-of-care (SoC) EGFR TKIs, gefinitib or afatinib, in patients with previously untreated EGFR-mutant advanced NSCLC.”
> “Model outcomes included costs (in 2018 Canadian dollars), life years (LYs), quality-adjusted life-years (QALYs), and the cost utility of osimertinib compared to SoC EGFR TKI, or incremental cost per QALY gained.”
Source: [Ezeife et al. (2018)](https://pubmed.ncbi.nlm.nih.gov/30429004/)
#### Utility weights for progression-free and progressed disease and adverse events, EGFR-mutated advanced NSCLC: Guan et al. (2019)
Relevance: Utilities for progression-free and progressed EGFR-mutated advanced non-small-cell lung cancer and disutilities for adverse events.
Access: Not open access
Not quoted: The utility weights are reported in the full text, which this page does not quote.
Source: [Guan et al. (2019)](https://pubmed.ncbi.nlm.nih.gov/31607559/)
### 2.4 Utility weights for related diseases and analogous treatments
#### Utility weights for progression-free disease and progression after first-line, second-line, and third-line therapy, RET fusion-positive advanced NSCLC: Liu et al. (2023)
Relevance: Utilities for progression-free non-small-cell lung cancer and for disease progression after first-line, second-line, and third-line therapy in a model of RET fusion-positive disease.
> “Health utility values were obtained for various states of NSCLC treatment (PFS, disease progression after first-line therapy, second-line therapy, third-line therapy, and death status) by referring to previously published studies on American NSCLC individuals.”
> “The utility values for these states were determined to be 0.71, 0.67, 0.59, 0.46, and 0, respectively”
Source: [Liu et al. (2023)](https://pmc.ncbi.nlm.nih.gov/articles/PMC10579832/)
## 3 Search strategy
| Dataset | Query | Results |
| --- | --- | --- |
| Ratios | zipalertinib OR "CLN-081" OR TAS6417 | 0 |
| Methods | ivonescimab OR zipalertinib OR zanzalintinib | 1 |
| Ratios | amivantamab | 7 |
| Ratios | "exon 20" OR "Exon 20" OR mobocertinib OR sunvozertinib | 3 |
| Ratios | EGFR AND "lung" | 348 |
| Ratios | "MARIPOSA-2" OR lazertinib | 7 |
| Ratios | T790M OR "AURA3" | 34 |
| Ratios | "EGFR" AND "second-line" | 67 |
| Weights | "EGFR" AND "lung" | 542 |
| Methods | "exon 20" OR "insertion" | 33 |
| Methods | amivantamab OR mobocertinib OR sunvozertinib | 4 |
| Weights | amivantamab OR "exon 20" | 13 |
| Ratios | sotorasib OR adagrasib | 6 |
| Ratios | selpercatinib OR pralsetinib | 2 |
| Ratios | capmatinib OR tepotinib | 3 |
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