Lung cancer is the malignant tumor with the highest incidence and mortality worldwide, with more than 2.2 million new cases each year. The 5‑year survival rate for advanced lung cancer is less than 15%, long limited by challenges including scarce targets, frequent drug resistance, and inconsistent efficacy of immunotherapy.

From 2025 to 2026, basic research and clinical translation in lung cancer have achieved explosive breakthroughs. New targets have been unlocked, immunotherapies innovated, and ADC drugs iterated. Multiple new drugs have been launched or entered clinical trials successively, completely reshaping the landscape of lung cancer treatment.

I.Breakthroughs in Basic Research: Unlocking the "Refractory Code" of Lung Cancer

1. Key Breakthroughs in Targeted Therapy: New Targets Unlocked, Resistance Overcome

Targeted therapy for lung cancer has entered an era of “full coverage across multiple targets.” Beyond classic targets such as EGFR and ALK, research on rare targets including MET, RET, and NTRK has advanced steadily from 2025 to 2026. Meanwhile, novel strategies targeting resistance mechanisms have been gradually implemented, offering patients long‑term survival hope.

（1）Chinese Teams Conquer EGFR‑TKI Resistance

A research team led by Prof. Lu Shun from Shanghai Chest Hospital, Shanghai Jiao Tong University, published the pivotal Phase III ORIENT-31 study in Lancet Oncology. It was the first to demonstrate that sintilimab (a PD‑1 inhibitor) combined with the bevacizumab biosimilar IBI305 plus chemotherapy significantly improves progression‑free survival (PFS) in patients with EGFR‑mutated non‑squamous non‑small cell lung cancer after progression on EGFR‑TKI therapy. This provides a new standard‑of‑care option for these resistant patients.

Source: Reference 1

（2） Studies on precision therapy for rare targets have been upgraded

Relevant research has shown that pralsetinib, a RET inhibitor, has demonstrated significant efficacy in patients with RET fusion‑positive advanced NSCLC in the ARROW trial. Currently, novel combination regimens using RET inhibitors represented by pralsetinib plus immune checkpoint inhibitors (such as atezolizumab) are under clinical investigation. Preliminary data suggest potential synergistic effects that may further prolong patient survival, providing a new strategy to overcome targeted therapy resistance and achieve long‑term benefit in rare target‑positive cancers.

2.Innovation in Immunotherapy: From Monotherapy to Combination Therapy, Covering More Patients

Lung cancer immunotherapy has fully moved from the "PD‑1/PD‑L1 monotherapy" era into a new era of "bispecific antibodies + combination therapy".In 2026, multiple studies broke through the bottlenecks of immunotherapy, enabling survival benefits for patients who originally did not respond to immunotherapy, while effectively reducing treatment toxicity.

（1）PD-L1/CTLA-4 Bispecific Antibody Breaks the Deadlock of Immunotherapy Non-Response

The team from Akeso Biotech announced the pivotal Phase Ib/II COMPASSION-03 study results in Lancet Oncology, evaluating the safety and anti-tumor activity of cadonilimab (PD-1/CTLA-4 bispecific antibody) in patients with advanced solid tumors. In the advanced non-small cell lung cancer cohort, this bispecific antibody demonstrated manageable safety and promising anti-tumor activity. Notably, clear clinical responses were observed even in traditionally immunotherapy-nonresponsive populations such as PD-L1-negative and low tumor mutational burden patients, providing a new direction to expand the beneficiary population of immunotherapy.

Source: Reference 2

（2）Cell Therapy Provides New Option for Immunotherapy-Resistant Advanced Lung Cancer

Dr. Kai He’s team published results from a multicenter Phase II clinical trial in the Journal for ImmunoTherapy of Cancer, evaluating the efficacy and safety of the autologous tumor-infiltrating lymphocyte (TIL) therapy lifileucel (LN-145) in patients with metastatic non-small cell lung cancer (mNSCLC) who progressed after chemotherapy and immune checkpoint inhibitor therapy.

Among 28 evaluable patients, the objective response rate (ORR) was 21.4% (6/28), including one complete metabolic response in a PD-L1‑negative patient. Median progression‑free survival (PFS) and overall survival (OS) were carefully monitored, and clinical responses were seen in typical immunotherapy‑resistant subgroups such as PD‑L1‑negative disease, low tumor mutational burden, and STK11 mutations. Although treatment‑related serious adverse events including cardiac failure were reported, the overall safety profile was manageable. This therapy offers a highly promising new treatment option for heavily pretreated mNSCLC patients.

Source: Reference 3（Efficacy outcomes by investigator assessment）

II Corporate Pipeline Expansion: Approved Drugs Scale Up, New Drugs Break Through Intensively

1.Approved Drugs: Solidifying the Cornerstone of Standard-of-Care Treatment

2.Clinical-stage new drugs: Targeted, Immunotherapy, and ADCs flourish across the board

(1) New Targeted Drugs: Covering Resistance Targets and Improving Long‑Term Benefit

(2) Immunotherapies and Bispecific Antibodies: Overcoming Non‑Response and Reducing Toxicity

PD-L1/TGF-β bispecific antibody (SHR-1701): Developed by Hengrui Medicine, used in combination with chemotherapy as first‑line treatment for advanced NSCLC.

CD47/PD-L1 bispecific antibody (AK127): Developed by Akeso Biotech for advanced NSCLC refractory to chemotherapy and immunotherapy, granted FDA Fast Track Designation.

(3) Other Innovative Therapies: Expanding Indications for ADCs and Tissue‑Agonistic Drugs

Larotrectinib: Developed by Bayer, an NTRK fusion inhibitor and tissue‑agnostic therapy. It achieves an ORR of 75% in NTRK fusion‑positive lung cancer patients, offering a precision option for those with rare mutations.

Disitamab Vedotin: Developed by Rongchang Biotech, a HER2 ADC for HER2‑low advanced NSCLC. In Phase II, it demonstrated an ORR of 40.2% and median PFS of 7.6 months, filling the treatment gap for HER2‑low lung cancer.

Reference

1. Lu S, Wu L, Jian H, et al. Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial. Lancet Oncol. 2022;23(9):1167-1179. doi:10.1016/S1470-2045(22)00382-5

2. Gao X, Xu N, Li Z, et al. Safety and antitumour activity of cadonilimab, an anti-PD-1/CTLA-4 bispecific antibody, for patients with advanced solid tumours (COMPASSION-03): a multicentre, open-label, phase 1b/2 trial. Lancet Oncol. 2023;24(10):1134-1146. doi:10.1016/S1470-2045(23)00411-4

3. Schoenfeld AJ, Lee SM, Doger de Spéville B, Gettinger SN, Häfliger S, Sukari A, Papa S, Rodríguez-Moreno JF, Graf Finckenstein F, Fiaz R, Catlett M, Chen G, Qi R, Masteller EL, Gontcharova V, He K. Lifileucel, an Autologous Tumor-Infiltrating Lymphocyte Monotherapy, in Patients with Advanced Non-Small Cell Lung Cancer Resistant to Immune Checkpoint Inhibitors. Cancer Discov. 2024 Aug 2;14(8):1389-1402. doi: 10.1158/2159-8290.CD-23-1334. PMID: 38563600; PMCID: PMC11294887.