Clinical Data Observations of ADCs at the 2026 ASCO Annual Meeting

Even before the formal opening of the 2026 ASCO Annual Meeting, Antibody-Drug Conjugates (ADCs) have emerged as one of the most highly anticipated areas of focus. Based on the abstracts and oral presentation information disclosed thus far, several distinct trends have materialized at this year's conference:

ADCs are expanding into more first-line treatment settings.
ADC-immunotherapy combinations have become a mainstream strategy.
Topoisomerase-I (Topo-I) payloads continue to dominate the industry.
Dual-target and bispecific ADCs have begun entering clinical validation stages.
Chinese enterprises have truly entered the global competitive landscape in core tracks such as lung cancer, HER2, HER3, and Nectin-4.

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Paradigm Shift in First-Line Therapy: OptiTROP-Lung05 Establishes a New Benchmark

In the field of first-line non-small cell lung cancer (NSCLC) treatment, the Phase III study (OptiTROP-Lung05) of Kelun-Biotech's sac-TMT (a Trop-2 ADC) combined with pembrolizumab is undoubtedly one of the most compelling data highlights at this ASCO.

Data Analysis: The study enrolled 413 patients with PD-L1 positive (TPS ≥1%) advanced first-line NSCLC, comparing an "ADC + immunotherapy" regimen against "immunotherapy monotherapy." Per Blinded Independent Central Review (BICR), the median Progression-Free Survival (PFS) in the combination arm has not yet been reached (NR), whereas the monotherapy arm reached 5.7 months. The Hazard Ratio (HR) was an impressive 0.35 (p<0.0001), demonstrating overwhelming statistical and clinical superiority.

More critically, the subgroup analysis showcased robust consistency: whether in populations with PD-L1 TPS 1-49% versus ≥50%, or across squamous versus non-squamous histological types, HR values were consistently maintained between 0.28–0.47 and 0.28–0.44, respectively. This signifies that the synergistic effect of sac-TMT manifests highly consistent clinical benefits across a heterogeneous lung cancer population. Although the combination arm saw a ≥3 grade Treatment-Emergent Adverse Event (TEAE) rate of 55.3% versus 31.4% in the monotherapy arm, the permanent discontinuation rate due to AEs was only 3.8%, demonstrating a manageable therapeutic window. The success of OptiTROP-Lung05 marks the formal challenge by ADC-IO combination therapies to the "throne" of first-line standard-of-care.

A New Definition for PD-L1 ADCs: The Mechanism and Potential of HLX43

Henlius’s HLX43, a PD-L1 targeted ADC, has also drawn significant attention at ASCO. HLX43 employs a high-payload strategy with a Drug-to-Antibody Ratio (DAR) of approximately 8. By utilizing target-mediated internalization and the "bystander effect," it aims to address immune evasion in PD-L1 high-expressing populations and the payload limitations of conventional ADCs.

Clinical Data Analysis: Summary data shows an overall Objective Response Rate (ORR) of 31.1% in 205 patients who had undergone multiple prior lines of therapy (median 2 lines). Of particular interest to researchers is its "biomarker-agnostic" potential—the ORR was 30.1% for the PD-L1 positive population and 32.1% for the PD-L1 negative population. This suggests that HLX43’s core advantage may lie in utilizing PD-L1 as a high-affinity "molecular anchor" to efficiently deliver topoisomerase inhibitors, thereby circumventing the traditional dependence on target expression levels.

In a randomized Phase II study for recurrent/metastatic Nasopharyngeal Carcinoma (r/m NPC), HLX43 demonstrated an ORR as high as 70.0% in the 3 mg/kg cohort, showcasing the drug's high response rate in specific tumor microenvironments. While the drug exhibited some toxicity regarding myelosuppression (e.g., decreased lymphocyte/white blood cell counts), its controllable discontinuation rate (8.3%) validates its potential for use in heavily pre-treated, drug-resistant populations.

Precision Engineering: Preliminary Success of Dual-Target ADCs

Chia Tai Tianqing’s TQB6411 introduces a new design philosophy for ADCs: dual-target precision regulation. By targeting both EGFR and c-Met, with a set affinity ratio of 2:1 (c-Met > EGFR), TQB6411 seeks a balance between killing efficiency and toxicity avoidance.

Safety and Efficacy Logic: In the first-in-human Phase I study (NCT07043751), dose escalation reached 6.6 mg/kg with no Dose-Limiting Toxicities (DLT). At doses ≥4 mg/kg, the ORR reached 50.0%, with a 100% Disease Control Rate (DCR). Regarding Interstitial Lung Disease (ILD)—the "Sword of Damocles" for ADC development—there were no reported cases of ILD in the 22 patients followed for at least 21 days. This early data supports the design rationale of the dual-target strategy in mitigating common cutaneous/pulmonary toxicities associated with EGFR inhibition.

Hengrui Medicine: Comprehensive Leadership in the ADC Matrix

Hengrui Medicine’s ADC pipeline matrix at ASCO reflects a comprehensive layout in target selection and clinical development speed:

SHR-A1811 (HER2 ADC): Achieved an 81.3% ORR in first-line colorectal cancer. As a competitor to DS-8201, SHR-A1811’s optimization in linker stability and bystander effects has allowed for strong performance in HER2-high expression populations.
SHR-A2009 (HER3 ADC): This project achieved Phase III success in second-line/late-line EGFR-mutated NSCLC, representing the world's first HER3 ADC to do so. In an increasingly crowded target space, Hengrui successfully captured a critical "blank space" following EGFR TKI resistance.
SHR-A2102 (Nectin-4 ADC): II/III phase data in muscle-invasive bladder cancer demonstrates an ORR exceeding current mainstream ADC benchmarks (e.g., Enfortumab vedotin), positioning the drug to potentially disrupt existing standards in frontline bladder cancer treatment.