The International Association for the Study of Lung Cancer (IASLC) 2026 World Conference on Lung Cancer (WCLC) brought the global thoracic oncology community to Seoul, Republic of Korea, from September 12–15. This year's theme, "Science Without Boundaries: Uniting the World Against Thoracic Cancer," was truly fitting for a meeting where research from Asia, Europe, and the Americas shaped the conversation around approaches to treating metastatic/advanced non-small cell lung cancer (NSCLC).
Longer survival follow-up, new first-line options for rare mutations, and a growing focus on healthcare delivery all took center stage at this year’s conference. Here are the highlights.
Bispecific Antibodies Are Stepping Forward and Likely to Become Part of Immunotherapy
Ivonescimab: Ivonescimab is a bispecific antibody that targets both PD-1 and VEGF pathways. The HARMONi-2 study looked at ivonescimab as first-line treatment for PD-L1-positive NSCLC. It improved median overall survival to 30.8 months, compared with 22.6 months for pembrolizumab, a current standard of care immunotherapy drug. Progression-free survival (PFS) nearly doubled (11.1 versus 5.8 months) and at three years, 45% of patients on ivonescimab were alive versus 33% on pembrolizumab. It’s important to note this trial was conducted in China. A global trial (HARMONi-7) is underway to test ivonescimab against pembrolizumab in people whose tumors make high levels of the PD-L1 protein. For people with EGFR-mutant NSCLC whose cancer grew during targeted therapy treatment, adding ivonescimab (HARMONi study) to chemotherapy extended overall survival to 16.8 months, compared with 14.0 months for chemotherapy alone. The benefit was the same in Western and Asian patients and this new treatment approach is currently being reviewed by the U.S. Food and Drug Administration.
Gotistobart: In the PRESERVE-003 study, squamous NSCLC that progressed after immunotherapy and chemotherapy, was treated with gotistobart, a next-generation anti-CTLA-4 antibody that nearly doubled median overall survival compared with the standard of care chemotherapy, docetaxel (18.5 versus 10.0 months). This data could offer an important new option for a group with few treatment choices.
Opamtistomig: The bispecific antibody, opamtistomig, targets the PD-L1 protein to reverse immune escape by cancer cells and the 4-1BB protein on cancer-fighting T cells. Exciting results in an early study showed that when opamtisomig is given in combination with chemotherapy, tumors shrank in 71% of people receiving it as first-line treatment. The drug showed strong activity when treating both squamous and non-squamous NSCLC. Additional studies are ongoing.
Targeted Therapy by Driver Mutation
EGFR: Final results from the phase 3 PAPILLON study showed that amivantamab plus chemotherapy produced a median overall survival rate of 34.3 months in patients with EGFR exon 20 insertion NSCLC. This is the longest reported median survival data to date for this group. In the phase 3 REZILIENT 3 study, adding zipalertinib, a tyrosine kinase inhibitor (TKI) that targets EGFR exon 20 insertions, to chemotherapy improved progression-free survival from 8.5 to 14.5 months and raised the response rate from 40% to 65%.
For people whose cancer develops the C797S resistance mutation, new drugs such as BH-30643 and VRN110755, are showing promise. These newer generation EGFR TKIs are more potent and are able to cross the blood-brain barrier to treat brain metastasis.
Finally, the phase 2b COPERNICUS study found that providing proactive skin and blood-clot prophylaxis to prevent side effects associated with subcutaneous amivantamab plus lazertinib. These adjustments reduced treatment discontinuations to under 1%, compared with 9% in the earlier MARIPOSA trial.
HER2: Zongertinib, a HER2 targeting TKI, is currently approved for the treatment of HER2-mutant NSCLC. It shrank tumors in 77% of patients with HER2-mutant NSCLC who hadn’t received any prior treatment, with disease controlled in 96%. This is particularly noteworthy because this population of patients often receives chemotherapy + immunotherapy (pembrolizumab) as the initial treatment. Separate studies are beginning to map how tumors become resistant to HER2-specific TKIs. For zongertinib, resistance varied widely between patients. For sevabertinib, another HER2 TKI, a secondary HER2 mutation called T862A was the most common resistance pathway. These findings will help guide what comes next for patients after progression.
ALK: Seven-year follow-up of the CROWN trial shows median survival with lorlatinib still has not been reached, confirming that lorlatinib is a strong first-line treatment option for ALK+ NSCLC. Most side effects, including those leading to dose reductions, appeared in the first two years and then leveled off. High cholesterol was manageable without an increase in heart problems. For people whose cancer progressed on second-generation ALK drugs, ficonalkib, another TKI, achieved a 43% response rate, with a 65% response rate in the brain, and a median progression-free survival of 9.7 months. Studies are underway to test this drug as a first-line option.
ROS1: Zidesamtinib is currently approved for the treatment of ROS1+ NSCLC that has been treated with other ROS1 TKIs. In the ARROS-1 trial, zidesamtinib shrank tumors in 94% of people who had not received a prior ROS1 TKI, and 86% of responses lasted at least a year. Every patient with measurable brain metastases responded, with 70% seeing their brain tumors disappear completely. Ninety percent remained progression-free at one year, making zidesamtinib a new option for newly diagnosed patients with ROS1+ NSCLC.
KRAS: KRAS G12D, a mutation with no approved targeted therapy, is seen in approximately 4% of patients with NSCLC. An oral KRAS G12D-blocking drug, called GFH375, achieved a 52% response rate and median progression-free survival of 8.3 months in patients who had received previous treatment. A phase 3 trial in this patient population with docetaxel as the control arm is currently enrolling. Similarly, another KRAS G12D inhibitor, QLC1101, also showed promising activity, with a 36% response rate. Studies are ongoing.
Antibody-Drug Conjugates May Become a First-Line Treatment Option
Antibody-drug conjugates (ADCs) deliver chemotherapy directly to cancer cells. In DESTINY-Lung04, the ADC trastuzumab deruxtecan (T-DXd) was compared with standard chemotherapy + pembrolizumab as initial treatment for HER2-positive NSCLC. T-DXd improved median progression-free survival rates from 8.3 to 14.3 months, and 70% of patients responded to ADC treatment versus 45% responding to chemotherapy. Responses also lasted longer (13.4 versus 9.7 months). It’s important to note that it’s too early to report the overall survival results. Lung inflammation (interstitial lung disease, or ILD) remains an important side effect in patients receiving T-Dxd. Early recognition of ILD is important to ensure symptoms can be managed appropriately.
We Are Learning How to Turn Scientific Progress Into Successful Healthcare Delivery
Matching treatment intensity to risk in EGFR-mutant NSCLC: Combination treatment may help most in people with higher-risk EGFR cancers, such as those with TP53 mutations. In the TOP trial for this group, adding chemotherapy to osimertinib more than doubled median progression-free survival (34.0 versus 15.6 months). Blood-based ctDNA testing may also help doctors decide when to add or remove treatment, an approach being tested in the FLAME and FLAURA2 Adaptive trials.
Biomarker testing is critical for the detection of rare oncogenic drivers: Rare drivers make up about 15% of NSCLC, with 21 FDA approvals over 10 years. Testing both DNA and RNA helps us find about 15% more patients with actionable gene fusions. Expert discussions at the meeting underscored the importance of getting comprehensive biomarker testing before the first treatment begins.
WCLC 2026 showed a field advancing on every front, from bispecific antibodies in immunotherapy to next-generation targeted drugs and ADCs moving into first-line care. Comprehensive biomarker testing, equitable access to new therapies, and research shaped by patient priorities will determine how many people benefit from these advances.
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