SCLC highlights from WCLC 2026

MAVERICK revisits the prophylactic cranial irradiation debate in SCLC

MRI surveillance preserved cognition without compromising survival in SCLC

Brain magnetic resonance imaging (MRI) alone improved cognitive outcomes without compromising survival compared with MRI plus prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), according to findings from the phase 3 SWOG S1827/MAVERICK trial presented at the 2026 World Conference on Lung Cancer (WCLC 2026).

Chad G. Rusthoven (University of Colorado, Aurora, USA) reported that MRI surveillance significantly improved cognitive failure-free survival (CFFS) compared with MRI plus PCI (HR, 0.60; 90% CI, 0.46–0.78; p=0.0005).

The benefit of MRI surveillance was observed across disease subgroups and was not influenced by disease stage or receipt of immunotherapy. Among patients with limited-stage (LS) disease, the HR for CFFS was 0.59, while in extensive-stage (ES) disease it was 0.65.

MAVERICK included 303 patients with LS-SCLC or ES-SCLC who had completed initial therapy and had no evidence of brain metastases on MRI. Patients were randomized 1:1 to MRI alone (n=151) or MRI plus PCI (25 Gy in 10 fractions; n=152). Brain MRIs were performed every 3 months during the first year and every 6 months during the second year. Most participants (68%) had LS-SCLC, and 41% had received immunotherapy as part of upfront treatment.

Despite a higher incidence of brain metastases with MRI alone, overall outcomes remained comparable between treatment strategies. At 12 months, brain metastases occurred in 30% of patients receiving MRI alone compared with 15% of those receiving MRI plus PCI. However, preliminary overall survival analyses conducted after 128 deaths showed no significant difference between the groups (HR, 0.90; 90% CI, 0.67–1.20), and progression-free survival was also similar (93 vs 91 events; HR 0.96; 90% CI, 0.75–1.23).

MRI alone was associated with substantially lower toxicity. Grade 3–5 treatment-related adverse events occurred in 0.8% of patients in the MRI-alone arm compared with 7.9% in the MRI plus PCI arm, which included one treatment-related grade 5 encephalopathy event.

Discussant Hideyuki Harada said the results strengthen the case for MRI surveillance in the modern era but cautioned that access to MRI remains a practical consideration. He also noted that the role of PCI in limited-stage SCLC may depend on mature overall survival data from MAVERICK and the ongoing PRIMALUNG trial.

B7-H3s in relapsed SCLC: Key findings from TAISHAN-302 and ARTEMIS-008

B7-H3 ADCs significantly improved survival versus topotecan in relapsed SCLC

Two phase 3 studies presented at WCLC 2026 demonstrated substantial survival benefits for B7-H3–targeted antibody–drug conjugates (ADCs) compared with topotecan in patients with relapsed small-cell lung cancer (SCLC), highlighting the growing potential of ADCs in the second-line setting.

Li Zhang (Sun Yat-sen University Cancer Center, Guangzhou, China) presented results from the phase 3 TAISHAN-302 trial evaluating tambotatug pelitecan (Tam-Peli). Among 451 patients randomized 1:1 to Tam-Peli (n=225) or topotecan (n=226), median overall survival (OS) was 13.3 months with Tam-Peli versus 9.4 months with topotecan (HR, 0.46; 95% CI, 0.35–0.62; p<0.0001). Median progression-free survival (PFS) was 7.4 versus 2.8 months, respectively, while objective response rates (ORR) were 59.1% and 9.7%. Notably, intracranial activity was also observed, with median intracranial PFS of 6.1 versus 4.2 months and intracranial ORR of 32.4% versus 2.9%.

Results from the ARTEMIS-008 trial, presented by Jie Wang (National Cancer Center, Beijing, China), showed similarly impressive efficacy for risvutatug rezetecan (Ris-Rez). In 461 patients with relapsed SCLC, median OS was 18.5 months with Ris-Rez (n=230) compared with 10.3 months with topotecan (n=231; HR, 0.46; 95% CI, 0.35–0.62; p<0.0001). Improvements were also seen in blinded-independent central review-assessed PFS (7.2 vs 3.0 months, respectively), ORR (58.3% vs 12.6%), and disease control rates (90.4% vs 60.2%). Benefits were consistent across predefined subgroups, including patients with brain metastases and those with a chemotherapy-free interval of <90 days.

Both ADCs demonstrated lower rates of grade ≥3 treatment-related adverse events than topotecan (46.4% vs 74.7% in TAISHAN-302, 60.9% vs 78.2% in ARTEMIS-008). Interstitial lung disease (ILD)/pneumonitis rates were relatively low with Tam-Peli (4.9%) versus topotecan (1.4%) but higher with Ris-Rez (11.7%) versus topotecan (1.9%), although no grade 4 or 5 ILD events were reported in either study.

Discussant Anne Chiang noted that both studies support B7-H3–targeted ADCs as emerging treatment options in relapsed SCLC. However, she cautioned that differences in study populations and both trials being conducted exclusively in China may limit cross-trial comparisons and global generalizability, while highlighting the need to better understand treatment sequencing as additional ADCs enter the field.

Tarlatamab studies explore alternative dosing strategies, subcutaneous administration, and toxicity prediction in SCLC

New data suggest that alternative tarlatamab dosing strategies and toxicity-prediction tools could further optimize treatment for relapsed SCLC

Several presentations at WCLC 2026 explored approaches to optimize the use of tarlatamab in small-cell lung cancer (SCLC), including alternative dosing schedules, subcutaneous administration, and imaging-based prediction of treatment-related toxicities.

In the phase 2 DeLLphi-309 study, Jonathan Goldman (University of California Los Angeles, USA) evaluated extended-interval dosing regimens of tarlatamab in patients whose disease had progressed after first-line platinum-based chemotherapy. Patients were randomized to receive the approved 10 mg every-2-weeks regimen (n=83), 20 mg every 3 weeks (n=84), or 30 mg every 4 weeks (n=85). Pharmacokinetic exposures were comparable across schedules, while blinded independent central review overall response rates (ORRs) were 39.8%, 31.0%, and 27.1%, respectively. Median progression-free survival (PFS) was 4.2, 4.1, and 2.7 months, respectively. Overall survival (OS) remained favorable across dosing regimens, with 6-month OS rates of 72%, 85%, and 69%, respectively. Safety profiles were broadly comparable, although serious treatment-related adverse events, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and treatment discontinuations were numerically higher with the extended-interval regimens. One fatal outcome, due to cardiac arrhythmia, was reported in the 30 mg every 4 weeks arm. The investigators concluded that alternative dosing schedules may offer greater treatment flexibility while maintaining activity.

Results from the phase 1b DeLLphi-308 study, presented by Pedro Rocha (Vall d’Hebron University Hospital and Institute of Oncology, Barcelona, Spain), provided the first evaluation of subcutaneous tarlatamab in previously treated extensive-stage SCLC (ES-SCLC). A 15 mg subcutaneous dose administered every 2 weeks achieved serum exposure comparable to that observed with 10 mg intravenous tarlatamab administered every 2 weeks and was associated with lower rates of CRS than reported historically with intravenous administration (DeLLphi-304), and all events were grade 1 or 2. Among 40 patients treated with the selected dose, ORR was 30%, median PFS was 3.7 months (95% CI, 1.9–7.0; median follow-up, 7.7 months), and median OS was 11.7 months (95% CI, 5.4–not estimable; median follow-up, 9.5 months). The phase 3 DeLLphi-315 trial is evaluating the safety and efficacy of subcutaneous versus intravenous tarlatamab in ES-SCLC.

A separate retrospective analysis presented by Lukas Delasos (Cleveland Clinic, Ohio, USA) explored whether baseline computed tomography (CT)-derived radiomic and vascular imaging features could identify patients at increased risk of CRS and ICANS during tarlatamab treatment. Pretreatment CT scans from 50 patients with ES-SCLC were analyzed using a linear discriminant analysis (LDA) framework. CRS and ICANS occurred in 56% and 20% of patients, respectively. Modeling of CT-derived radiomic and vascular imaging features achieved an area under the curve (AUC) of 0.81 (95% CI, 0.80–0.82) and 0.88 (95% CI, 0.87–0.90) for predicting CRS and ICANS, respectively. Clinicopathologic factors alone were not predictive of toxicity risk. The investigators noted that imaging-based risk stratification could help tailor monitoring strategies and improve management of immune-related adverse events associated with DLL3-targeted T-cell engagers.

MRI surveillance, ADCs, and T-cell engagers: Key SCLC advances from WCLC 2026 by Giannis Mountzios

Giannis Mountzios, MD, PhD, discusses key advances in small-cell lung cancer (SCLC) from WCLC 2026, including the implications of MAVERICK for MRI surveillance and prophylactic cranial irradiation (PCI), phase 3 findings for B7-H3–targeted antibody–drug conjugates (ADCs) in relapsed disease, and emerging T-cell engager strategies. He also considers how treatment combinations, sequencing, and patient selection may shape future SCLC care. View transcript.

Chapters
00:00 What do you consider to be the most important advances in SCC presented at WCLC 2026?
00:39 What are your key takeaways from the MAVERICK study? How might these findings influence the role of PCI and MRI surveillance in SCLC?
04:40 TAISHAN-302 and ARTEMIS-008 evaluated B7-H3–targeted ADCs in relapsed SCLC. What stands out from these findings? 
06:26 Several presentations explored T-cell engagers in SCLC. What developments stood out to you? 
09:05 Following WCLC 2026, where do you see the greatest opportunities and remaining unmet needs in SCLC?
 

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