FDA Approvals That Changed Lung Cancer Treatment in 2025
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Clinical Transformation in Lung Cancer Treatment Algorithms in 2025: FDA Approvals
2025 was a year of biomarker-driven treatments and more convenient administration in lung cancer oncology. Antibody-drug conjugates (ADCs) and bispecific technologies established new standards after chemotherapy. In this review, we examine the clinical trial outcomes and safety data for 10 key treatments approved in 2025.
1. Non-Small Cell Lung Cancer (NSCLC)
Telisotuzumab Vedotin (c-Met ADC)
Population: Metastatic nonsquamous NSCLC that progressed after platinum-based treatment, with wild-type EGFR and high c-Met expression (H-score ≥150).
LUMINOSITY Data: ORR 35%; median PFS 6.0 months.
Safety: The most common adverse effects are peripheral neuropathy (25%) and ocular toxicity (keratopathy). The rate of Grade 3+ adverse events is 15%.
Taletrectinib (ROS1 TKI)
Population: ROS1 fusion-positive metastatic NSCLC, including both TKI-naive and crizotinib-resistant patients.
TRUST-I/II Analysis: ORR 92% in the TKI-naive arm; intracranial ORR 80% in patients with brain metastases.
Safety: GI toxicity (nausea/diarrhea) 40%, AST/ALT elevation 20% (mostly Grade 1-2).
Datopotamab Deruxtecan (TROP2 ADC)
Population: Metastatic NSCLC with an accompanying genomic mutation (EGFR/ALK) and progression after targeted therapy.
TROPION-Lung01/05: A 25% reduction in the risk of progression compared with standard docetaxel (HR: 0.75).
Safety: Stomatitis (45%) is the most common adverse effect. The reported rate of ILD (interstitial lung disease) was 8%.
Sunvozertinib (EGFR Exon 20 TKI)
Population: Patients with EGFR Exon 20 insertion mutations whose disease progressed during or after platinum-based chemotherapy.
WU-KONG Analysis: ORR 61%; median DoR (duration of response) has not yet been reached.
Safety: Diarrhea (60%) and rash (50%) are the most common; elevated CPK requires clinical monitoring.
Zongertinib (HER2-Selective TKI)
Population: Nonsquamous NSCLC harboring a HER2 tyrosine kinase domain (TKD) mutation.
Beamion LUNG-1: ORR 67%. High brain penetration.
Safety: Its selectivity results in very low EGFR-related toxicity (severe diarrhea).
2. Small Cell Lung Cancer (SCLC)
Lurbinectedin + Atezolizumab (Maintenance)
Population: Extensive-stage disease (ES-SCLC) that is stable or responding after first-line platinum+etoposide+atezolizumab.
IMforte Study: Median PFS: 4.4 months (control: 2.3 months); HR: 0.54.
Safety: Neutropenia (30%) and anemia (20%) may occur at Grade 3+ severity.
Tarlatamab-dlle (Bispecific BiTE)
Population: Relapsed/refractory ES-SCLC that has progressed after at least two lines of systemic therapy.
DeLLphi-301: ORR 40%; median OS 14.3 months. The strongest second-line data in SCLC in the past 10 years.
Safety: Cytokine release syndrome (CRS) 50% (usually Grade 1-2); neurological events (ICANS) 10%.
3. The Subcutaneous (SC) Administration Revolution
Pembrolizumab SC (Keytruda Qlex)
Clinical Benefit: A 3-minute subcutaneous injection instead of a 30-60-minute IV infusion.
MK-3475A-D77: Pharmacokinetic (C-trough) and efficacy equivalence to the IV formulation was demonstrated. Injection-site reactions occur in less than 10%.
Amivantamab SC (Rybrevant Faspro)
Population: NSCLC with an EGFR Exon 19 deletion or L858R mutation.
PALOMA-3: The infusion reaction rate fell from 65% with the IV formulation to 13% with SC administration. A numerical overall survival (OS) advantage over the IV group was observed (HR: 0.62).
DROZDOGAN Academy Commentary
The 2025 approvals are accelerating the shift toward "chemotherapy-free options" in metastatic lung cancer. Tarlatamab is helping reprogram the immune system in SCLC; Amivantamab SC is making adverse-effect management easier; and c-Met-directed ADCs are achieving success, helping standardize oncology practice. For clinicians, the greatest challenge now is to move comprehensive genomic profiling (NGS) to the start of treatment so that they can choose "the right drug at the right time" from this expanding armamentarium.
Sources
Taletrectinib: FDA Oncology Bulletin (June 11, 2025). Combined Analysis of TRUST-I and TRUST-II Trials. Lancet Oncology. NCT04395612.
Datopotamab Deruxtecan: FDA Approval Bulletin (June 23, 2025). TROPION-Lung01 and TROPION-Lung05 Trials. NEJM, 2024. NCT04656652.
Sunvozertinib: FDA Center for Drug Evaluation (July 2, 2025). WU-KONG6 Study for EGFR Exon 20. The Lancet, 2024. NCT05712213.
HER2 TKI (Zongertinib): FDA Approvals (Aug-Nov 2025). Beamion LUNG-1 Primary Results. ESMO Congress Proceedings. NCT05244473.
Lurbinectedin + Atezolizumab: FDA News (Oct 2, 2025). Phase 3 IMforte Trial Maintenance Therapy. Annals of Oncology. NCT05091567.
Tarlatamab-dlle: FDA Full Approval (Nov 19, 2025). DeLLphi-301 and DeLLphi-304 Results. NEJM, 2024. NCT05060016.
Pembrolizumab SC: FDA (Sep 19, 2025). MK-3475A-D77 Subcutaneous Formulation Efficacy Study. ClinicalTrials.gov NCT04586270.
Amivantamab SC: FDA (Dec 17, 2025). PALOMA-3 Phase 3 Study: IV vs SC Comparison. Journal of Thoracic Oncology (JTO). NCT05388669.
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