Dr Federico Monaca discusses eight major abstracts in lung cancer from ASCO 2026
The 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago showed that thoracic oncology is moving beyond promising signals and increasingly closer to practice-changing evidence across multiple fields — from bispecific antibodies and ADC-based combinations to targeted therapy in both metastatic and peri-operative settings. In this piece, Dr Federico Monaca (The Christie NHS Foundation Trust, UK) breaks down eight major abstracts from ASCO 2026, highlighting their take-aways and considering their potential relevance for clinical practice.
touchONCOLOGY coverage of ASCO 2026
HARMONi-6
→ Abstract LBA4: Zhiwei C, Yang F, Luo Y, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in previously untreated advanced squamous non–small cell lung cancer: Overall survival results of the phase 3 HARMONi-6 trial. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
One of the most practice-relevant updates came from HARMONi-6, evaluating ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in the first-line treatment of advanced squamous non-small cell lung cancer. The reported overall survival benefit supports the biological rationale of dual PD-1/VEGF targeting and positions ivonescimab as the most mature agent in the PD-1/VEGF bispecific class. However, interpretation still requires caution. The study was conducted in China, and tislelizumab is not the standard immunotherapy backbone in many Western countries. Therefore, while the OS signal is impressive, global validation remains essential before this regimen can be considered broadly practice-changing outside China.
The broader PD-1/VEGF bispecific field was also represented by early data with pumitamig and PF-08634404. These agents showed high response rates, particularly in squamous NSCLC, but the datasets remain less mature and largely non-comparative. The key message is that PD-1/VEGF bispecifics are clearly active, but the field is becoming crowded. Ivonescimab currently leads because it has phase III survival data, whereas other agents will need to demonstrate not only activity, but also a favourable safety profile, global reproducibility and superiority against relevant contemporary standards. It is plausible that several agents in this class may ultimately show broadly similar efficacy, making differentiation dependent on tolerability, convenience, regulatory speed and the quality of comparative evidence.
WU-KONG28
→ Abstract LBA8500: Heymach JV, Liu G, Xing L, et al. Sunvozertinib monotherapy versus platinum-based chemotherapy as first-line treatment for advanced NSCLC with EGFR exon20ins: Primary analysis of a multinational phase 3 randomized study (WU-KONG28). Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
In EGFR exon 20 insertion-positive NSCLC, WU-KONG28 added important frontline data for sunvozertinib. The appeal is clear: an oral targeted agent that improves outcomes compared with chemotherapy and may be easier to deliver than antibody-based regimens. However, the exon 20 space is now complex. Amivantamab plus chemotherapy has already changed the standard while sunvozertinib offers a different balance of convenience, toxicity and efficacy. Key unanswered questions remain: CNS activity, optimal dose, benefit in non-Asian populations, efficacy across near-loop versus far-loop insertions, and how best to sequence sunvozertinib with amivantamab-based strategies.
OptiTROP-Lung05
→ Abstract 8506: Zhou C, Xiong A, Yao W, et al. Sacituzumab tirumotecan (sac-TMT) plus pembrolizumab (P) versus pembrolizumab (P) as first-line treatment for PD-L1–positive advanced non-small cell lung cancer (NSCLC): Results from the randomized phase 3 OptiTROP-Lung05 study. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
Another important signal came from OptiTROP-Lung05, which evaluated sacituzumab tirumotecan plus pembrolizumab in PD-L1-positive advanced NSCLC. This is relevant because it represents one of the first phase III attempts to move an ADC plus immunotherapy combination into the first-line setting. The magnitude of the PFS and ORR benefit appears substantial, and sacituzumab-TMT is emerging as one of the most promising ADCs in lung cancer. However, the comparator arm is a major limitation: pembrolizumab monotherapy is not a global standard of care for many patients with PD-L1 1–49%, where chemo-immunotherapy would usually be preferred. This likely contributes to the apparently stronger benefit in PD-L1-low patients. In addition, toxicity was meaningfully increased, and CNS efficacy remains unclear. Mature OS data and global validation will determine whether this is truly a new standard or a strong signal requiring a more appropriate confirmatory strategy.
CHRYSALIS-2
→ Abstract 8501: Neal JW, Cho BC, Wang Y, et al. MATRiX: Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): Updated results from the CHRYSALIS-2 study. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026
Atypical EGFR mutations also remain an area of rapid evolution. Updated CHRYSALIS-2 data with amivantamab plus lazertinib suggest clinically meaningful long-term benefit in atypical EGFR-mutant NSCLC, with particularly impressive survival data for a population historically treated with heterogeneous and often suboptimal approaches. Silevertinib is also interesting, especially because of its CNS activity signal in non-classical EGFR mutations. However, high dose-reduction rates (77%) and gastrointestinal and skin toxicity raise important questions about the optimal therapeutic window.
CROWN
→ Abstract 8502: Mok TS, Solomon BJ, Felip E, et al. Lorlatinib vs crizotinib as first-line treatment for advanced ALK+ non-small cell lung cancer: 7-year update from the phase 3 CROWN study. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
ALK-positive NSCLC was another major theme. The 7-year CROWN update with lorlatinib continues to redefine expectations for first-line ALK inhibition. Median PFS remains not reached, with durable systemic and intracranial disease control that is unprecedented in advanced ALK-positive disease. This reinforces lorlatinib as arguably the most effective first-line ALK inhibitor. However, the discussion cannot focus only on efficacy. Hyperlipidaemia, weight gain, oedema, neuropathy and cognitive effects are clinically meaningful, especially for patients expected to remain on treatment for many years. In clinical practice, the goal should be proactive toxicity management, with early recognition of adverse events and timely consideration of dose reduction if needed.
LORIN
→ Abstract 8002: Zhang C, Hu Y, Jiang BY, et al. Neoadjuvant lorlatinib in stage III NSCLC harboring ALK fusion: A phase 2 multicenter study (LORIN). Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
The LORIN study extended the lorlatinib discussion into early-stage disease. Peri-operative lorlatinib in stage III ALK-positive NSCLC produced striking pathological activity, including high pCR and MPR rates, marked nodal downstaging and high R0 resection rates among patients who underwent surgery. This is particularly notable because pathological responses with neoadjuvant targeted therapy have historically been less dramatic than those seen with chemo-immunotherapy in oncogene-negative disease. LORIN therefore raises the possibility that potent ALK inhibition may become a future peri-operative paradigm. Nevertheless, the data remain early. The study was single-arm, China-only and relatively small; a substantial proportion of patients did not proceed to surgery; and EFS and OS are not yet mature. In addition, the role and duration of adjuvant therapy after pCR remain unclear. Given the established benefit of adjuvant alectinib from ALINA, future studies will need to clarify whether peri-operative lorlatinib adds meaningful long-term benefit beyond current adjuvant strategies.
ALKOVE-1
→ Abstract 8503: Lin JJ, Felip E, Cho BC, et al. ALKOVE-1: Efficacy and safety of neladalkib in patients with advanced ALK+ NSCLC. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
In the post-lorlatinib setting, ALKOVE-1 with neladalkib addressed a major emerging unmet need. As first-line ALK therapy becomes more effective, the population progressing after lorlatinib will become increasingly difficult to treat. Neladalkib showed activity in heavily pretreated ALK-positive NSCLC, including patients with prior lorlatinib exposure and ALK resistance mutations such as G1202R. The overall activity is encouraging, but the post-lorlatinib PFS signal appears modest, underscoring the challenge of this setting. The future role of neladalkib may depend on molecular selection, intracranial activity and whether it can demonstrate sufficient benefit after modern sequential ALK inhibitors. Importantly, with CROWN setting such a high benchmark for first-line therapy, the greatest need may be for effective second-line and later options rather than another first-line competitor.
DeLLphi-304
→ Abstract 8006: Mountzios GS, Cho BC, Phil Lammers, et al. Intracranial efficacy of tarlatamab versus chemotherapy (CTx) as second-line (2L) treatment for small cell lung cancer (SCLC): DeLLphi-304 phase 3 post hoc analysis. Presented at: ASCO, Chicago, IL, USA. May 29 to June 2, 2026.
In small cell lung cancer, Mountzios et al. in DeLLphi-304 addressed one of the most clinically relevant questions for tarlatamab: intracranial efficacy. Brain metastases are common in SCLC, and systemic agents with meaningful CNS activity are urgently needed. The post-hoc CNS analysis supports the activity of tarlatamab in patients with baseline brain metastases and strengthens its role as a key second-line option after platinum-based therapy.
This content has been developed independently by Touch Medical Media for touchDERMATOLOGY in collaboration with Dr Federico Monaca. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Disclosure: Federico Monaca has nothing to disclose in relation to this interview.
Cite: Lung cancer at ASCO 2026: Key takeaways. touchONCOLOGY. 9th June 2026.
Editor: Sophie Nickelson, Editorial Director
