SCLC and NSCLC therapeutic landscape Report Interpretation

Overview

This WCLC 2026 deep dive compares emerging therapies across small-cell and non-small-cell lung cancer, with emphasis on B7-H3 and TROP2 ADCs and PD-1-based bispecific antibodies. Bernstein concludes that SCLC survival benchmarks are improving, while in the larger first-line PD-L1 all-comer NSCLC setting, TROP2 ADCs offer the clearest adoption path because they combine competitive efficacy with a comparatively balanced safety profile.

Core views

In first-line extensive-stage SCLC, Bernstein argues that novel targeted therapies are moving survival expectations well beyond the roughly 13-month median overall survival delivered by PD-L1 plus chemotherapy. Tarlatamab has shown median OS above 25 months from maintenance initiation. MediLink/Roche's B7-H3 ADC YL201 plus serplulimab reported an 85% objective response rate and 12.9 months of median PFS, compared with approximately five months for the historical standard-of-care benchmark; however, its OS data remain immature. Bernstein views these results as evidence that targeted approaches are steadily improving first-line SCLC outcomes. For relapsed ES-SCLC, the report identifies B7-H3 ADCs as potential new standards of care because YL201 and Hansoh/GSK's HS-20093 both produced statistically significant OS improvements over topotecan in randomized Phase 3 trials. HS-20093 reported median OS of 18.5 months, median PFS of 7.2 months and an OS hazard ratio of 0.46, the longest numerically reported survival among comparable late-line SCLC studies in Bernstein's comparison. YL201 extended median PFS from roughly five months to 13 months and also showed an OS benefit. Safety was considered manageable, although grade 3 or higher treatment-related adverse events were about 46% for YL201 and 61% for HS-20093; interstitial lung disease occurred with ADCs, with YL201 showing the lowest rate across the compared trials. Bernstein considers HS-20093 better positioned for global category leadership because its Phase 3 development is broader and supported by GSK's global platform, while YL201's late-stage program is more concentrated. In first-line PD-L1 all-comer NSCLC, the report frames the contest as a race between bispecific antibodies and ADCs to displace Keytruda plus chemotherapy. PD-1-based bispecifics currently lead on response rate: RemeGen/AbbVie's RC148 posted ORRs of 90% in squamous and 75.9% in non-squamous NSCLC, while Innovent's IBI363 reported 85.7% and 87.5%, respectively. Bernstein cautions that much of this evidence is early stage, so response rates may compress in larger registrational studies. On PFS, AK112 remains the bispecific benchmark at 11.1 months in squamous NSCLC, while sac-TMT and Datroway have produced durability signals generally around 11-12 months; sac-TMT reported 15.4 months median PFS in a Phase 2 setting. Bernstein treats overall survival as the decisive endpoint for establishing a new first-line standard. AK112 has the strongest mature evidence: at 36 months' follow-up in HARMONi-2, its OS hazard ratio improved to 0.73 versus Keytruda, with median OS of 30.8 months versus 22.6 months. The benefit was stronger in the PD-L1 TPS at least 50% subgroup, with an OS hazard ratio of 0.58, and in squamous NSCLC, at 0.65. Datroway has shown the most advanced ADC OS signal, with median OS near 29 months in TROP2-positive patients, although data for many other programs, including sac-TMT, remain immature. Bernstein notes that sac-TMT plus pembrolizumab showed more favorable PFS hazard ratios than HARMONi-2 in certain subgroups, especially non-squamous disease and PD-L1 TPS 1-49%, but cross-trial comparisons have limits. On safety, Bernstein sees IBI363's optimized 3-to-1.5 mg/kg regimen as an improvement, reducing grade 3 or higher TEAEs from 81.3% to 65.2% while largely retaining efficacy. It considers PD-1xVEGF toxicity broadly manageable and comparable with chemo-immunotherapy standards. For ADCs, sac-TMT is highlighted for favorable pulmonary safety and one of the lowest ILD rates among leading TROP2 ADCs, though it retains expected class toxicities including stomatitis, nausea and hematologic adverse events. The institution ultimately favors TROP2 ADCs, especially sac-TMT, for their balance of survival potential and safety; it identifies the expected ESMO 2026 OptiTROP-Lung06 readout and Datroway's AVANZAR data as pivotal tests of whether TROP2 ADCs can become a first-line NSCLC backbone. The report also reviews later-line NSCLC. In I/O-treated squamous NSCLC, Hengrui's SHR-A1921 achieved median PFS of 7.3 months and was described as second only to IBI363 in the field. In I/O-treated actionable-genomic-alteration-negative non-squamous NSCLC, IBI363 showed median OS of 17.5 months in the lower-dose group and 15.2 months in the higher-dose group, with better grade 3 treatment-related safety than HS-20093 in the report's comparison. In EGFR-mutated NSCLC after EGFR-TKI failure, HARMONi's final OS analysis showed an OS hazard ratio of 0.76 in both Western and Asian populations, while sac-TMT delivered 8.3 months median PFS in Phase 2 actionable-genomic-alteration-positive NSCLC.

Analysis framework

Bernstein compares WCLC clinical datasets across treatment line, tumor histology, biomarker population, efficacy endpoints and safety. It prioritizes mature overall-survival evidence over early response-rate signals, while using PFS, objective response rate, grade 3 or higher adverse events, ILD incidence and development-stage breadth to assess differentiation. The report repeatedly notes that cross-trial comparisons should be interpreted cautiously.

Methodology notes

• Industry AnalysisVolume-price decomposition

  Cross-program comparison of response rates, PFS, OS and adverse-event rates

  The report separates clinical efficacy into response, progression-free survival and overall survival, and compares these measures with safety data to judge competitive positioning.

• Competition & strategyEconomic Moat and Competitive Advantage

  Clinical differentiation and global development strategy

  Bernstein assesses whether a program's efficacy, safety profile, maturity of evidence and breadth of global Phase 3 trials can create an advantage over competing therapies.

Asset mapping & comparison

Structured mapping from thesis to named assets (strengths, weaknesses, peers, risks).

• Kelun-Biotech (6990.HK) / sac-TMT

  Covered company and Bernstein's preferred exposure among the reviewed China oncology names

  Strengths

  Balanced survival and safety profile; 15.4 months mPFS reported in a Phase 2 first-line NSCLC setting; favorable pulmonary safety profile.

  Weaknesses

  Overall-survival data remain immature.

  Comparison

  Bernstein favors TROP2 ADCs versus bispecifics on overall efficacy-safety balance; Datroway currently has more advanced ADC OS evidence.

  Risks

  OptiTROP-Lung06 results must confirm competitiveness in the first-line setting.

• Innovent (1801.HK) / IBI363

  Covered company with an early-stage PD-1xIL-2 bispecific program

  Strengths

  High ORRs of 85.7% in squamous and 87.5% in non-squamous first-line NSCLC; later-line OS of 17.5 months in the lower-dose non-squamous cohort.

  Weaknesses

  Early-stage evidence and initially high grade 3 or higher TEAE rate.

  Comparison

  Ranks near the top of bispecific programs on ORR, but mature OS evidence is less developed than AK112.

  Risks

  Response rates may compress in larger registrational trials; safety remains an important consideration.

• Hansoh (3692.HK) / HS-20093

  Covered company with a B7-H3 ADC program

  Strengths

  18.5 months mOS and OS HR of 0.46 versus topotecan in relapsed ES-SCLC; broad global development support through GSK.

  Weaknesses

  Grade 3 or higher treatment-related adverse events were about 61%, above YL201's reported level.

  Comparison

  Has a global-development advantage versus YL201, while YL201 appeared somewhat cleaner on safety.

  Risks

  Hematologic toxicity and ILD remain relevant ADC class risks.

• Akeso (9926.HK) / AK112

  Covered company with a PD-1xVEGF bispecific program

  Strengths

  Most mature first-line NSCLC OS evidence in the report: 30.8 months mOS and statistically significant OS HR of 0.73 versus Keytruda.

  Weaknesses

  The report rates Akeso Market-Perform.

  Comparison

  Leads on mature bispecific OS data; sac-TMT showed lower PFS hazard ratios in selected subgroup comparisons.

  Risks

  Competitive differentiation will depend on future ADC and bispecific readouts.

Key data

• First-line ES-SCLC standard-of-care median OSRoughly 13 monthsPD-L1 plus chemotherapy benchmark cited by Bernstein
• Tarlatamab first-line ES-SCLC median OSOver 25 monthsMeasured from maintenance initiation
• YL201 first-line ES-SCLC efficacy85% ORR; 12.9 months mPFSOS remains immature
• HS-20093 relapsed ES-SCLC efficacy18.5 months mOS; 7.2 months mPFS; OS HR 0.46Versus topotecan in Phase 3
• AK112 HARMONi-2 OS update30.8 months versus 22.6 months; OS HR 0.73At 36 months' follow-up versus Keytruda
• Datroway first-line NSCLC OS signalNearly 29 months mOSIn TROP2-positive patients
• sac-TMT first-line NSCLC PFS15.4 months mPFSPhase 2 result cited in the report

Impact & implications

Bernstein believes the clinical landscape is shifting from chemo-immunotherapy toward targeted combinations. B7-H3 ADCs could alter treatment in relapsed SCLC, while the first-line NSCLC market remains unsettled because early bispecific response advantages must be confirmed by mature survival and safety evidence. The institution sees upcoming Phase 3 results as decisive for TROP2 ADC adoption.

Risks

• Overall-survival data remain immature for many emerging first-line NSCLC programs, including sac-TMT and several bispecific antibodies.
• Early response-rate results may decline as programs move into larger registrational trials.
• ADC development carries class risks including hematologic toxicity and interstitial lung disease.

What to watch

• Phase 3 OptiTROP-Lung06 results for sac-TMT, expected at ESMO 2026.
• Datroway's AVANZAR readout in first-line NSCLC.
• Whether mature OS data validate early response and PFS signals for competing bispecific and ADC programs.
• Global Phase 3 execution by HS-20093 and YL201 in SCLC and other solid tumors.