The full FDA approval of trastuzumab deruxtecan for HER2-mutant NSCLC in January 2026 marks the arrival of antibody-drug conjugates as a mainstream lung cancer treatment class, triggering a competitive ADC development wave across HER2, HER3, TROP2, and MET targets that is fundamentally reshaping the thoracic oncology commercial landscape.

DESTINY-Lung02 trial data demonstrating a 49.0% confirmed objective response rate with T-DXd in HER2-mutant NSCLC has reshaped clinical thinking about what is achievable in a previously poorly-addressed patient population. AstraZeneca and Daiichi Sankyo's collaborative commercial model for T-DXd is being watched by global pharma strategists as a template for high-cost oncology biologic co-commercialization. For oncology pharmacists and tumor board chairs at U.S. comprehensive cancer centers, NCI-designated cancer centers, and major European cancer centers in London, Paris, Milan, and Amsterdam, the arrival of T-DXd for NSCLC requires immediate formulary review, patient selection algorithm development, and toxicity management protocol creation. The lung cancer ADC therapy development and market forecast positions HER2-mutant NSCLC as one of the fastest-growing biomarker-defined therapeutic segments in thoracic oncology through 2030.

TROP2-Directed ADCs Challenge Docetaxel in Second-Line NSCLC

Datopotamab deruxtecan (Dato-DXd), developed through the AstraZeneca-Daiichi Sankyo collaboration, is generating significant clinical interest for its activity in TROP2-expressing NSCLC — a broader population than HER2-mutant patients. Phase III data from the TROPION-Lung08 trial, presented at ESMO 2025 and published in early 2026, demonstrated datopotamab deruxtecan's superiority over docetaxel in the second-line setting, with a particularly favorable safety profile attracting attention from oncologists managing elderly NSCLC patients who cannot tolerate conventional chemotherapy toxicities. The regulatory submission for datopotamab deruxtecan in NSCLC is pending at both the FDA and EMA in 2026, with approval decisions expected in H2 2026. These approvals represent significant inflection points for the commercial planning of oncology systems in the United States, Germany, France, the United Kingdom, Japan, and Canada — markets that collectively account for over 70% of global branded NSCLC drug spending. Accessing the AI-powered U.S. lung cancer treatment market intelligence is essential for formulary and contracting teams modeling the budget impact of datopotamab deruxtecan's anticipated approval.

MET-Directed ADCs Enter Phase II with Promising Early Data

MET exon 14 skipping mutations and MET amplification represent approximately 3–5% of NSCLC cases collectively. Telisotuzumab vedotin (Teliso-V), developed by AbbVie, reported encouraging data in a Phase II basket trial published in early 2026, showing 34.6% overall response rates in MET-high NSCLC patients — including in patients who had already progressed on crizotinib or capmatinib. This finding suggests that the ADC mechanism may circumvent some resistance pathways intrinsic to small-molecule MET blockade. Clinical trial design discussions are now underway about sequencing strategies between MET small molecules and MET-directed ADCs, a clinical optimization question that major trial sites in Houston, Boston, New York, London, and Tokyo are beginning to address through institutional protocols and investigator-initiated trials. The intersection of MET-directed ADC development with broader precision oncology infrastructure investments creates a notable opportunity for health systems in cities with high concentrations of thoracic oncology expertise and NGS-profiled patient populations.

ADC Toxicity Management Becomes a Competitive Differentiator

As ADCs proliferate in lung cancer treatment, the clinical community is increasingly focused on managing class-specific toxicities — particularly interstitial lung disease associated with DXd-payload ADCs, and peripheral neuropathy associated with vedotin-payload agents. The FDA issued a class-wide safety communication on ADC-associated ILD risk in November 2025, and the ESMO Clinical Practice Guidelines for ADC Toxicity Management — expected in Q2 2026 — will provide the first comprehensive guidance framework for oncology teams managing multiple concurrent ADC regimens. Pharmaceutical companies competing in the ADC space are increasingly differentiating on the basis of toxicity profile and monitoring program support rather than purely on efficacy signals, as clinician comfort with manageable toxicity pathways becomes a key treatment adoption driver across community oncology networks in the United States, Germany, France, Italy, the United Kingdom, and Japan — markets where patient volume, reimbursement infrastructure, and clinical practice density are most favorable for early ADC commercialization success.

Trending News 2026

ADCs just rewrote the NSCLC treatment algorithm — and at least 3 more approvals are expected this year