Lung cancer remains one of the leading causes of cancer-related deaths worldwide, underscoring the critical need for continuous therapeutic innovation. While significant strides have been made in treatment, many patients—particularly those with resistance to first-line therapies or harboring difficult-to-treat mutations—still face limited options.

In the first half of 2025, the U.S. Food and Drug Administration (FDA) approved four novel therapies for lung cancer: Emrelis (telisotuzumab vedotin), Taletrectinib (Ibtrozi), Datopotamab deruxtecan-dlnk (Datroway), and Zegfrovy (sunvozertinib). These approvals reflect a clear trend toward precision-targeted treatments and mechanistic diversity, particularly in the areas of antibody-drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs).

Table 1: Overview of FDA-Approved Lung Cancer Therapies in H1 2025

1. Emrelis (Telisotuzumab Vedotin)

Emrelis is an innovative ADC engineered to selectively target the c-Met receptor tyrosine kinase. It comprises an anti–c-Met monoclonal antibody, a cleavable linker, and the potent cytotoxic agent MMAE.

On May 14, 2025, the FDA granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis) for adults with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by an FDA-approved test, who have received a prior systemic therapy.

The approval was based on the positive results of the LUMINOSITY Phase II trial (NCT03539536), where Emrelis demonstrated an objective response rate (ORR) of 35% (95% CI: 24–46) and a median duration of response (DoR) of 7.2 months. The safety profile was consistent with prior studies, with common adverse events including peripheral neuropathy, fatigue, and decreased appetite. [1]

Developed by AbbVie, Emrelis is the company’s first internally developed solid tumor drug and a significant milestone in its oncology pipeline. AbbVie is also conducting a global Phase III confirmatory trial (TeliMET NSCLC-01) to evaluate Emrelis monotherapy in previously treated c-Met–overexpressing NSCLC patients. [1]

As the first and only approved therapy for this patient population, Emrelis addresses a significant unmet clinical need. Its approval underscores the clinical value of ADCs in oncology and the importance of companion diagnostics in selecting patients most likely to benefit from targeted treatment.

2. Taletrectinib (Ibtrozi) 

Taletrectinib is an oral, potent, CNS-active, selective, next-generation ROS1 tyrosine kinase inhibitor (TKI). On June 11, 2025, the FDA approved taletrectinib (Ibtrozi) for adults with locally advanced or metastatic ROS1-positive NSCLC.

This FDA approval was supported by two Phase II single-arm studies—TRUST-I (NCT04395677) and TRUST-II (NCT04919811): [2]

For ROS1-positive NSCLC patients previously treated with ROS1 TKIs (n=113):

• • In the TRUST-I study (n=66), the cORR was 52%, with a median DoR of 13.2 months and a median follow-up of 33 months.
• • In the TRUST-II study (n=47), the cORR was 62%, with a median DoR of 19.4 months and a median follow-up of 19 months.

For ROS1-positive NSCLC patients who were ROS1 TKI–naïve (n=157):

• • In the TRUST-I study (n=103), the cORR was 90% and the median DoR was not yet reached. At a median follow-up of 40 months, the longest ongoing DoR observed was 46.9 months.
• • In the TRUST-II study (n=54), the cORR was 85%, with the median DoR also not reached. At a median follow-up of 19 months, the longest ongoing DoR observed was 30.4 months.

In addition, across both studies, intracranial objective response rates (iORR) in ROS1-positive NSCLC patients with brain metastases were 63% (15/24) in previously treated patients and 73% (11/15) in treatment-naïve patients.

Taletrectinib demonstrated a favorable safety profile with low incidence of neurologic adverse events—most being Grade 1, such as dizziness (21%) and dysgeusia (15%)—an improvement over existing ROS1 inhibitors like entrectinib and repotrectinib.

Taletrectinib’s approval represents a significant step forward for ROS1-positive NSCLC. Its unique characteristics, particularly the lower rate of neurological toxicity and robust CNS activity, make it an attractive option.

3. Datopotamab Deruxtecan-dlnk (Datroway) 

Datroway is a TROP2-directed ADC comprised of a humanized monoclonal antibody linked to a topoisomerase I inhibitor (DXd) via a cleavable tetrapeptide-based linker. Co-developed by Daiichi Sankyo and AstraZeneca, Datroway received two key FDA approvals:

• • January 17, 2025: For adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative  unresectable or metastatic breast cancer who have received prior endocrine-based therapy and chemotherapy. (based on TROPION-Breast01). [3]
• • June 23, 2025: Accelerated approval for locally advanced or metastatic EGFR-mutated NSCLC post–EGFR TKI and platinum chemotherapy—marking the first FDA-approved TROP2 ADC for lung cancer.  (Based on TROPION-Lung05 and TROPION-Lung01) [4]

In the TROPION-Lung05 and TROPION-Lung01 trials, Datroway achieved a cORR of 45% (95% confidence interval [CI]: 35–54) in 114 patients with previously treated, locally advanced or metastatic EGFR-mutant NSCLC, as assessed by a blinded independent central review (BICR). Among these patients, 4.4% achieved complete responses (CR) and 40% achieved partial responses (PR). The median DoR was 6.5 months (95% CI: 4.2–8.4).

Compared with traditional chemotherapy, Datopotamab deruxtecan offers a clear efficacy advantage. In patients with EGFR-mutant NSCLC who have developed resistance to prior treatments, standard chemotherapy typically results in an ORR of less than 20%. Datroway nearly doubles this rate to 45%, offering a notable improvement in tumor response. Furthermore, its longer duration of response underscores its superior therapeutic benefit, providing a more effective treatment option for this challenging patient population.

Despite competition in breast cancer—possibly even from Enhertu (another Daiichi/AstraZeneca ADC)—Datroway holds significant potential in NSCLC. While the initial broad BLA was withdrawn and resubmitted for a narrower EGFR-mutated population, EvaluatePharma still forecasts $4.29 billion in 2030 sales, confirming its blockbuster potential.

4. Zegfrovy (Sunvozertinib) 

ZEGFROVY is an oral, irreversible EGFR inhibitor with a uniquely designed molecular structure targeting a wide spectrum of EGFR mutations with wild-type EGFR selectivity. On July 2, 2025, the FDA granted accelerated approval to sunvozertinib (Zegfrovy) for locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, following progression on or intolerance to platinum chemotherapy.

Developed by Dizal (Jiangsu) Pharmaceutical, Zegfrovy was first approved in China in August 2023, becoming the first globally approved oral therapy for EGFR exon20ins NSCLC. It had previously received breakthrough therapy designation from both the FDA and China’s CDE.

The FDA approval was based on the Phase II WU-KONG1B trial (NCT03974022), where 85 platinum-pretreated patients showed:

• • ORR: 46% (95% CI: 35–57)
• • Median DoR: 11.1 months

An expanded cohort (n=107) showed a best ORR of 53.3%, with 2.8% achieving complete response. Anti-tumor activity was observed regardless of baseline brain metastases or prior amivantamab treatment. Zegfrovy’s safety profile was favorable, with most treatment-emergent adverse events (e.g., diarrhea, rash, CPK elevation) being Grade 1–2 and manageable. [6]

Zegfrovy’s approval represents a major advance in treating EGFR exon20ins NSCLC, a mutation class historically resistant to first-generation EGFR TKIs. Its oral administration further improves patient convenience and potential adherence.

Conclusion

The first half of 2025 marked a pivotal period in lung cancer therapeutics, with four groundbreaking FDA approvals. Emrelis, Taletrectinib, Datroway, and Zegfrovy each provide molecularly targeted solutions for specific NSCLC subtypes, including c-Met overexpression, ROS1 fusion, and EGFR exon20ins mutations.

These therapies address key unmet medical needs, particularly in heavily pretreated or brain-metastatic populations. They reflect a growing emphasis on precision medicine, biomarker-driven drug development, and global collaboration, laying a strong foundation for continued innovation in lung cancer care.

References:
[1] https://news.abbvie.com/2025-05-14-U-S-FDA-Approves-EMRELIS-TM-telisotuzumab-vedotin-tllv-for-Adults-With-Previously-Treated-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-With-High-c-Met-Protein-Overexpression
[2] https://investors.nuvationbio.com/news/news-details/2025/U-S--Food-and-Drug-Administration-Approves-Nuvation-Bios-IBTROZI-taletrectinib-a-Next-Generation-Oral-Treatment-for-Advanced-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx
[3] https://www.astrazeneca.com/media-centre/press-releases/2025/dato-dxd-approved-in-us-for-hr-p-breast-cancer.html
[4] https://www.astrazeneca.com/media-centre/press-releases/2025/datroway-approved-in-us-for-egfrm-lung-cancer.html
[5] https://www.onclive.com/view/fda-grants-accelerated-approval-to-sunvozertinib-for-nsclc-with-egfr-exon-20-insertion-mutations
[6] https://www.oncnursingnews.com/view/sunvozertinib-granted-fda-accelerated-approval-in-egfr-exon-20-nsclc