The 2026 ASCO Annual Meeting featured numerous high-impact studies in lung cancer. To help readers identify the presentations with the greatest potential to influence clinical practice, The ASCO Post asked lung cancer specialist Apar Kishor Ganti, MD, MS, FASCO, to share his top picks. Dr. Ganti is Professor in the Division of Medical Oncology and holds the Dr. and Mrs. D. Leon University of Nebraska Medical Center (UNMC) Research Fund Chair in Internal Medicine at UNMC in Omaha.
Here are his selections and perspectives on their findings.
TRIPLEX in SCLC: Adding Thoracic Radiotherapy to Chemoimmunotherapy
Building on prior studies of thoracic radiotherapy in extensive-stage small cell lung cancer (SCLC), the phase III TRIPLEX trial evaluated whether its concurrent use with chemoimmunotherapy could improve overall survival. Bjørn Henning Grønberg, MD, PhD, of St. Olav’s University Hospital, Trondheim, Norway, presented the findings.1
A total of 228 treatment-naive patients were randomly assigned in a 1:1 ratio to receive carboplatin, etoposide, and durvalumab with or without thoracic radiotherapy (initiated 3 to 4 weeks after treatment began), but the trial was stopped early following a recommendation from the Data and Safety Monitoring Committee. Dr. Ganti pointed out that concurrent thoracic radiotherapy increased the risk of adverse events without improving overall survival, overall response rate, or progression-free survival.
“This study is another in a list of studies that have shown no benefit to adding immunotherapy during either radiation or chemoradiation in lung cancer,” he told The ASCO Post.
LIBRETTO-432: Adjuvant Selpercatinib in RET Fusion–Positive NSCLC
Although RET fusions occur in only 1% to 2% of lung cancers, Jonathan W. Goldman, MD, of the University of California, Los Angeles, emphasized during a press briefing that “rarity should not be mistaken for marginal importance,” given the high risk of recurrence in these patients. The phase III LIBRETTO-432 trial evaluated whether adjuvant therapy with the brain-penetrant RET inhibitor selpercatinib could delay or prevent recurrence.2
LIBRETTO-432 was a randomized (1:1), double-blind, placebo-controlled phase III trial evaluating up to 3 years of adjuvant selpercatinib vs placebo in 151 patients with stage IB to IIIA RET fusion–positive non–small cell lung cancer (NSCLC) following curative-intent surgery or radiotherapy, with or without adjuvant chemotherapy. The primary endpoint was investigator-assessed event-free survival in those with stage II to IIIA disease (n = 109).
Selpercatinib was found to significantly improve investigator-assessed event-free survival compared with placebo (hazard ratio [HR] = 0.172; P = .0003). A total of 91.5% vs 61.1% of patients, respectively, remained event-free at 24 months.
“These results are consistent with those seen in the ADAURA and ALINA trials, which studied other patients with early-stage lung cancer with an actionable genomic alteration, namely,” Dr. Ganti explained. Echoing the investigators’ conclusion, he added: “It is critical to obtain comprehensive genomic profiling in all patients with NSCLC.”
HARMONi-6: Ivonescimab Plus Chemotherapy vs Tislelizumab in Squamous NSCLC
With PD-(L)1 inhibitor–based chemoimmunotherapy established as first-line treatment for advanced squamous NSCLC, the phase III HARMONi-6 trial compared the anti–PD-1/VEGF bispecific antibody ivonescimab plus chemotherapy (paclitaxel and carboplatin) with the anti–PD-1 monoclonal antibody tislelizumab-jsgr plus chemotherapy.3 A total of 532 patients were randomly assigned in a 1:1 ratio to receive up to four cycles of one of the two chemoimmunotherapy regimens, followed by maintenance immunotherapy.
The prespecified overall survival interim analysis, presented at the meeting by Shun Lu, MD, PhD, of Shanghai Chest Hospital in Shanghai, China, demonstrated a significant improvement in this endpoint with ivonescimab (27.9 vs 23.7 months; HR = 0.66; one-sided P = .0017).
However, Dr. Ganti cautioned that “while this was a significantly positive trial, it was conducted entirely in China. The control arm included tislelizumab, an agent that is not routinely used in the United States. The results of the ongoing HARMONi-3 trial will determine the role of ivonescimab in advanced NSCLC.”
WU-KONG28: Sunvozertinib vs Chemotherapy for NSCLC With EGFR Exon 20 Insertion
Following its accelerated approval for advanced NSCLC harboring EGFR exon 20 insertion mutations that had progressed on or after platinum-based chemotherapy, sunvozertinib was evaluated as first-line therapy in the multinational phase III WU-KONG28 trial.4 Presented by John V. Heymach, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston, the study compared the EGFR tyrosine kinase inhibitor monotherapy with platinum-based chemotherapy.
A total of 324 patients were randomly assigned in a 1:1 ratio to receive either sunvozertinib or chemotherapy (carboplatin/pemetrexed). Those in the chemotherapy group were permitted to cross over to sunvozertinib after disease progression.
Sunvozertinib was found to significantly improve progression-free survival compared with chemotherapy (median, 10.3 vs 7.5 months; HR = 0.65; P = .0008). It also achieved a higher confirmed objective response rate (58.9% vs 31.1%) and longer duration of response (median, 11.2 vs 7.1 months).
“The WU-KONG28 trial did not use amivantamab plus chemotherapy, which is the current standard of care for these patients based on the PAPILLON study,” Dr. Ganti remarked. “Despite this, sunvozertinib represents a chemotherapy-free option for these patients.”
He added, “It remains to be seen whether the addition of chemotherapy to sunvozertinib, à la FLAURA2, will improve outcomes even further.”
CROWN: First-Line Lorlatinib vs Crizotinib in Advanced ALK-Positive NSCLC
Following what the study authors described as an “unprecedented” progression-free survival benefit with the ALK tyrosine kinase inhibitor lorlatinib after 5 years in the phase III CROWN trial, lead author Tony S. K. Mok, MD, FRCPC, FASCO, presented a post hoc analysis of longer-term outcomes.5
Dr. Mok is Chairman and Li Shu Fan Medical Foundation Endowed Professor in the Department of Clinical Oncology with the State Key Laboratory of Translational Oncology at The Chinese University of Hong Kong in China.
In the trial, treatment-naive patients with advanced ALK-positive NSCLC were randomly assigned to receive lorlatinib (n = 149) or crizotinib (n = 147). After 7 years of follow-up, median progression-free survival remained unreached with lorlatinib (vs 9.1 months with crizotinib; HR = 0.19, 95% confidence interval [CI] = 0.13–0.26). In the lorlatinib arm, patients who remained progression-free at 2 years had a 79% probability of survival without progressive disease at 7 years.
“These studies show that the benefit seen with lorlatinib is highly durable,” Dr. Ganti remarked.
EA5142: Nivolumab After Surgery and Adjuvant Chemotherapy in NSCLC
The phase III ECOG-ACRIN EA5142 trial, part of the National Cancer Institute’s ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials) program, was conducted to fill a therapeutic need in completely resected EGFR/ALK-negative nonsquamous NSCLC and open an opportunity for squamous, according to presenting author Jamie E. Chaft, MD, FASCO, of Memorial Sloan Kettering Cancer Center, New York.6
A total of 935 patients with resected stage IB to IIIA squamous or EGFR/ALK-negative nonsquamous disease were randomly assigned in a 1:1 ratio to receive nivolumab for up to 1 year or standard-of-care observation following all planned adjuvant therapy. After a median follow-up of 72.6 months, nivolumab did not appear to significantly improve disease-free survival in the intention-to-treat population, nor did it among patients with tumor PD-L1 expression of at least 50%.
Reflecting on the negative findings, Dr. Ganti stated, “These results contrast with those seen with adjuvant atezolizumab (IMpower010) and pembrolizumab (KEYNOTE-091). One possible explanation could be the liberal time to postoperative enrollment in this study, as this allowed enrollment between 28 and 300 days after surgery.”
ROSETTA Lung-02: First-Line Pumitamig Plus Chemotherapy in NSCLC
Among the novel immunotherapy-based approaches presented at the meeting was the investigational PD-L1 × VEGF-A bispecific antibody pumitamig, plus chemotherapy. Solange Peters, MD, PhD, of Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, presented the phase II portion of the ongoing global phase II/III ROSETTA Lung-02 trial, which evaluated the recommended phase III dose of the investigational agent in treatment-naive patients with advanced NSCLC without actionable genomic alterations.7
A total of 44 patients were randomly assigned in a 1:1 ratio to receive pumitamig at either 1,400 mg or 2,000 mg in combination with histology-specific chemotherapy. “Encouraging” overall response rates were observed with both doses across both histologies in the 40 response-evaluable patients, Dr. Peters pointed out, although the 1,400-mg dose was associated with numerically higher confirmed rates in both nonsquamous (63.6% vs 50.0%) and squamous (72.7% vs 62.5%) NSCLC. Treatment-emergent immune-related adverse events occurred in 37.2% (grade ≥ 3: 4.7%) of patients, and bleeding events in 20.9% (grade ≥ 3: 2.3%).
“Based on the overall trial data, pumitamig 1,500 mg [as a] flat dose every 3 weeks was chosen for the phase III part of the trial based on [pharmacokinetic and pharmacodynamic] modeling,” Dr. Peters said.
Putting the findings into a broader context, Dr. Ganti remarked, “With similar promising results being seen in the ivonescimab trials, inhibition of PD-L1 and VEGF together may be better than blocking the PD-(L)1 pathway alone in NSCLC.”
OptiTROP-Lung05: First-Line Sacituzumab Tirumotecan Plus Pembrolizumab for PD-L1–Positive Advanced NSCLC
Presented by Caicun Zhou, MD, PhD, ABFT, of Shanghai East Hospital, Tongji University, the phase III OptiTROP-Lung05 trial evaluated whether adding the TROP2-directed antibody-drug conjugate sacituzumab tirumotecan to first-line anti–PD-(L)1 therapy could improve outcomes in patients with PD-L1–positive advanced NSCLC without EGFR or ALK alterations.8
Patients were randomly assigned to receive sacituzumab tirumotecan plus pembrolizumab (n = 208) or pembrolizumab alone (n = 205). Dr. Ganti highlighted the significant blinded independent central review (BICR)-assessed progression-free survival benefit observed in the planned interim analysis with sacituzumab tirumotecan plus pembrolizumab (median, not reached vs 5.7 months; HR = 0.35; P < .0001). In a prespecified subgroup analysis, this improvement was observed regardless of PD-L1 tumor proportion score (TPS), with HRs of 0.28 (95% CI = 0.19–0.41) among patients with a TPS of 1% to 49% and 0.47 (95% CI = 0.29–0.77) among those with a TPS of at least 50%—a finding he described as “interesting.” The BICR-assessed objective response rate was also higher with the combination (70.2% vs 42.0%).
Sacituzumab tirumotecan was associated with stomatitis and myelosuppression, Dr. Ganti noted.
“While it can be argued that the standard of care in this population is chemoimmunotherapy rather than pembrolizumab alone,” he commented, “the impressive results in the high PD-L1–expressing group suggest that this combination may be superior to pembrolizumab alone.”
Central vs Local Lab PD-L1 Classification in NSCLC
Not all of Dr. Ganti’s selections focused on new therapies. One study examined the consistency of PD-L1 testing in NSCLC, with David E. Kozono, MD, PhD, of Mass General Brigham Cancer Institute, Boston, presenting a poster on an analysis of the ALCHEMIST adjuvant immunotherapy study screening population. Dr. Ganti described the findings as “sobering” and said they “could impact clinical care significantly.”9
The investigators identified 497 patients with resected stage II to IIIB(N2) NSCLC who had both central and local PD-L1 results. Of these, 177 (36%) had discrepant results that placed patients in different clinical TPS categories (< 1%, 1% to < 50%, or 50% to 100%). Three expert pathologists rereviewed digitally scanned slides in a blinded fashion.
On rereview of the same scanned PD-L1 slides, pairwise disagreement between the pathologists regarding clinical TPS category was similar for the 177 cases with initially discrepant central and local results and 46 randomly selected nondiscrepant controls (mean disagreement, 27% vs 28%).
Among 43 cases with large initial discrepancies (≥ 50 percentage points), 14 had local testing slides available for rereview. When the three pathologists rereviewed the paired central and local slides, the slides were assigned to the same clinical TPS category in 54%, 38%, and 43% of cases, respectively, across the three reviewers, despite complete discordance between the initial central and local assessments. Agreement rates were higher when the slides originated from the same vs different tumor blocks (100% vs 35%), when the same vs different PD-L1 antibodies were used (48% vs 40%), and in nonsquamous vs squamous NSCLC (52% vs 14%).
“[These results] could explain the relatively imperfect performance of PD-L1 expression as a predictive biomarker,” Dr. Ganti commented. “Artificial intelligence–based models could potentially decrease the heterogeneity in these results.”
DISCLOSURE: Dr. Ganti has served as a consultant for AstraZeneca, Cardinal Health, Jazz Pharmaceuticals, Catalyst Pharmaceuticals, Boehringer Ingelheim, and Fosun Pharma; and has received institutional research support from Apexigen, Nektar Therapeutics, Merck, Pfizer, Boehringer Ingelheim, Poseida, Mirati Therapeutics, Imugene, and Iovance. For full disclosures of the study authors, visit meetings.asco.org.
REFERENCES
1. Gronberg BH, Dumoulin DW, Oselin K, et al: Concurrent thoracic radiotherapy, platinum/etoposide chemotherapy, and durvalumab immunotherapy in extensive-stage small cell lung cancer: A phase III trial. 2026 ASCO Annual Meeting. Abstract LBA8005. Presented June 1, 2026.
2. Goldman JW, Yang X, Hochmair M, et al: Event-free survival with adjuvant selpercatinib in stage IB-IIIA RET fusion-positive NSCLC: Primary results of the phase 3 LIBRETTO-432 trial. 2026 ASCO Annual Meeting. Abstract LBA3. Presented May 31, 2026.
3. 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. 2026 ASCO Annual Meeting. Abstract LBA4. Presented May 31, 2026.
4. 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). 2026 ASCO Annual Meeting. Abstract LBA8500. Presented May 29, 2026.
5. 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. 2026 ASCO Annual Meeting. Abstract 8502. Presented May 29, 2026.
6. Chaft JE, Sun Z, Rudin CM, et al: Randomized phase III study of nivolumab after surgery and adjuvant chemotherapy in NSCLC (ECOG-ACRIN EA5142, ALCHEMIST). 2026 ASCO Annual Meeting. Abstract 8000. Presented June 1, 2026.
7. Peters S, Lee Y, Erman M, et al: Phase 2 data from ROSETTA Lung-02, a global randomized phase 2/3 trial of pumitamig (PD-L1 × VEGF-A bsAb) + chemotherapy in 1L NSCLC. 2026 ASCO Annual Meeting. Abstract 8513. Presented May 30, 2026.
8. Zhou C, Xiong A, Yao W, et al: Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab as first-line treatment for PD-L1–positive advanced non-small cell lung cancer: Results from the randomized phase 3 OptiTROP-Lung05 study. 2026 ASCO Annual Meeting. Abstract 8506. Presented May 29, 2026.
9. Kozono DE, Giri S, Hillman SL, et al: Differences in central versus local lab PD-L1 classification in the ALCHEMIST Alliance A151216 non–small cell lung cancer (NSCLC) study. 2026 ASCO Annual Meeting. Abstract 8057. Presented May 31, 2026.
