2025 FDA Lung Cancer Approvals: Precision Medicine and Immunotherapy Advances

The year 2025 has been a pivotal period for thoracic oncology, characterized by a series of landmark approvals from the FDA that further segment the treatment landscape of non–small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The regulatory decisions this year have largely emphasized the role of precision medicine, with the introduction of novel antibody-drug conjugates (ADCs) and next-generation tyrosine kinase inhibitors (TKIs) targeting specific molecular alterations. Additionally, new strategies in the maintenance setting for SCLC have provided much-needed options for this aggressive disease.

Expanding the Role of Antibody-Drug Conjugates

A significant development in 2025 was the expansion of ADCs into new biomarker-defined subgroups of NSCLC. On June 23, 2025, the FDA granted accelerated approval to datopotamab deruxtecan-dlnk(Dato-DXd; Datroway) for the treatment of adult patients with locally advanced or metastatic EGFR-mutated NSCLC who have received prior EGFR-directed therapy and platinum-based chemotherapy.¹ This approval, based on efficacy data from the TROPION-Lung01 (NCT04656652) and TROPION-Lung05 (NCT04484142) trials, established TROP2 as a validated therapeutic target in lung cancer. The approval addresses a critical unmet need for patients who exhaust standard TKIs and chemotherapy, offering a targeted alternative to traditional salvage regimens.

Earlier in the year, on May 14, 2025, the FDA granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis), a c-Met–directed ADC.² It is indicated for adult patients with advanced or metastatic non-quamous NSCLC with high c-Met protein overexpression (defined as ≥50% of tumor cells with strong staining) whose disease has progressed on or after prior systemic therapy. This approval underscores the importance of immunohistochemistry (IHC) testing for c-Met in the refractory setting.

Next-Generation Tyrosine Kinase Inhibitors

The year 2025 also saw the arrival of highly selective TKIs designed to overcome resistance or target rare mutations with greater precision.

On August 8, 2025, the FDA granted accelerated approval to zongertinib (Hernexeos) for adult patients with unresectable or metastatic non-squamous NSCLC harboring HER2 (ERBB2) tyrosine kinase domain (TKD) mutations.³ Approval was supported by the Beamion LUNG-1 trial (NCT04886804), which demonstrated an objective response rate (ORR) of 75% in patients previously treated with platinum-based chemotherapy. Zongertinib’s design allows it to spare wild-type EGFR, potentially reducing off-target toxicities such as rash and diarrhea that have limited the utility of earlier pan-HER inhibitors.

Additionally, on June 11, 2025, the FDA approved taletrectinib (Ibtrozi) for adult patients with locally advanced or metastatic ROS1-positive NSCLC.⁴ Taletrectinib is a next-generation TKI capable of crossing the blood-brain barrier, addressing the high incidence of central nervous system metastases in this population.

Advances in Small Cell Lung Cancer

Progress in SCLC in 2025 focused on extending survival and cementing the role of immunotherapy. On October 2, 2025, the FDA approved the combination of lurbinectedin (Zepzelca) and atezolizumab (Tecentriq) for the maintenance treatment of adult patients with extensive-stage SCLC (ES-SCLC) whose disease has not progressed following first-line induction therapy with atezolizumab and chemotherapy.⁵ This approval was based on the phase 3 IMforte trial (NCT05091567), which showed a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) compared with atezolizumab maintenance alone.

Furthermore, on November 19, 2025, the FDA granted full approval to tarlatamab-dlle (Imdelltra), a bispecific T-cell engager (BiTE) targeting DLL3.⁶ Initially granted accelerated approval, this agent is now fully indicated for patients with ES-SCLC with disease progression on or after platinum-based chemotherapy. The conversion to full approval followed results from the phase 3 DeLLphi-304 study (NCT05060016), confirming its survival benefit in a heavily pretreated population.

Conclusion

The approvals of 2025 highlight a clear trajectory toward highly individualized care in lung cancer. The successful integration of TROP2- and c-Met–directed ADCs, alongside HER2- and ROS1-specific TKIs, mandates more comprehensive molecular and protein expression profiling at diagnosis and progression. As these novel agents enter clinical practice, multidisciplinary teams must navigate new toxicity profiles and sequencing strategies to optimize patient outcomes.

REFERENCES

1. FDA grants accelerated approval to datopotamab deruxtecan-dlnk for EGFR-mutated non-small cell lung cancer. News release. US FDA. June 23, 2025. Accessed December 22, 2025. https://tinyurl.com/mu5spftb

2. U.S. FDA approves Emrelis (telisotuzumab vedotin-tllv) for adults with previously treated advanced non-small cell lung cancer (NSCLC) with high c-Met protein overexpression. News release. AbbVie/ May 14, 2025. Accessed December 22, 2025. https://tinyurl.com/yeytkv73

3. FDA grants accelerated approval to zongertinib for non-squamous NSCLC with HER2 TKD activating mutations. News release. US FDA. August 8, 2025. Accessed December 22, 2025. https://tinyurl.com/fbakh64s

4. FDA approves taletrectinib for ROS1-positive non-small cell lung cancer. News release. US FDA. June 11, 2025. Accessed December 22, 2025. https://tinyurl.com/4v5bkvfh

5. FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer. FDA. October 2, 2025. Accessed December 22, 2025. https://tinyurl.com/2pc8wf2b

6. FDA grants traditional approval to tarlatamab-dlle for extensive-stage small-cell lung cancer. FDA. November 19, 2025. Accessed December 22, 2025. https://tinyurl.com/ycy7hety