Positive New Drug Data for Lung Cancer at ASCO, Key Global Trial Results Still Pending Validation

Overview

This report is based on the 2026 ASCO conference and focuses on two cutting-edge areas in first-line non-small cell lung cancer (NSCLC) therapy: MRK/Kelun’s TROP2-targeted antibody–drug conjugate (Sac-TMT) and PD(L)1xVEGF bispecific antibodies (represented by SMMT/Akeso’s Ivonescimab, BMY/BNTX’s Pumitamig, and PFE’s PF'4404). The report systematically reviews key clinical data, assesses the strengths and limitations of these therapies, and analyzes their potential impact on the relevant pharmaceutical companies. Core conclusion: While the new drug data are encouraging, the generalizability across global populations and overall survival benefits will require validation from pivotal trials in the second half of 2026.

Core views

Regarding Sac-TMT (MRK/Kelun): In China’s Phase III OptiTROP-Lung05 trial, among PD-L1-positive patients, Sac-TMT plus Keytruda vs. Keytruda alone resulted in an unmet median PFS versus 5.7 months (p<0.0001); hazard ratios were 0.28 in the TPS 1–49% subgroup and 0.47 in the ≥50% subgroup. BICR-assessed ORR was 70.2% vs. 42.0%. Safety-wise, Grade 3+ TEAEs occurred in 55.3% of patients, primarily hematologic toxicities and mucositis, but permanent discontinuation rates were low (3.8%/5.3%). The report finds these results broadly consistent with expectations, but the more critical global Phase III OptiTROP-Lung06 trial (vs. Keytruda plus chemotherapy in PD-L1-negative non-squamous NSCLC) is scheduled for release in the second half of 2026. Sac-TMT’s global development plan spans NSCLC, breast cancer, gynecologic malignancies, and other indications; success could significantly expand its market opportunity. Morgan Stanley projects a risk-adjusted 2035 sales figure of $4.1 billion (55% probability of success), below the market consensus of $5.4 billion. Turning to PD(L)1xVEGF bispecific antibodies: SMMT/Akeso’s Ivonescimab reported a median OS of 27.9 vs. 23.7 months in the Chinese Phase III HARMONi-6 trial (squamous NSCLC; HR=0.66), marking the first OS benefit observed in this class. However, limitations include a follow-up duration of only 21.4 months, lack of benefit in patients aged 65 and older (HR=0.93), and a predominantly male cohort (96%) that excluded those over 75. The report stresses that the 2026 second-half data from the global Phase III HARMONi-3 trial (vs. Keytruda plus chemotherapy) will be even more decisive. Meanwhile, BMY/BNTX’s Pumitamig (global Phase II Rosetta-Lung02) achieved ORRs of 48%–100% across all PD-L1 expression levels; PFE’s PF'4404 (Chinese Phase II) recorded an ORR of 68% and a median PFS of 12.4 months at the 10 mg dose. The report forecasts Pumitamig’s risk-adjusted 2035 sales at $5.6 billion (50%–70% success probability), and PF'4404 at $2.7 billion (50%). Background and Landscape: First-line NSCLC therapy is currently dominated by Merck’s Keytruda (patent expiring in 2028). These emerging therapies aim to either improve upon or replace Keytruda; Merck, with both Sac-TMT and LM-299 (a PD-1xVEGF bispecific), holds a unique strategic advantage by being positioned in both前沿 directions.

Analysis framework

The report employs a three-tiered analytical framework—clinical data–commercial potential–company mapping: First, it dissects core endpoints such as PFS, OS, ORR, and safety, drawing on ASCO’s published results and conducting subgroup analyses (by PD-L1 level, histology, age) to delineate the boundaries of each drug’s applicability. Second, it compares these findings against historical Keytruda trial data (e.g., the KEYNOTE series) and cross-trial outcomes within the same class, explicitly noting the typical limitations of such comparisons (population and design differences). Third, it highlights critical design flaws in the trials (e.g., the representativeness of the Chinese cohort in HARMONi-6, the short follow-up period), underscoring the importance of subsequent global trials (HARMONi-3, OptiTROP-Lung06) for definitive validation. Finally, it maps clinical progress onto corporate pipeline value, incorporating risk-adjusted sales forecasts and relative ratings to inform investment perspectives.

Methodology notes

• Industry/Industrial Analysis Framework

  Hierarchical Interpretation of Clinical Trial Endpoints (PFS/OS/ORR/Subgroups)

  In pharmaceutical research reports, attention is not limited to primary endpoints (e.g., whether PFS is significantly prolonged); rather, subgroup analyses (e.g., stratified by PD-L1 level or age) help determine the boundaries of the applicable patient population. At the same time, follow-up duration and statistical maturity (e.g., whether OS data are driven by a single event) are considered to assess the robustness of the conclusions.

• Valuation Methodology

  Risk-Adjusted Sales Forecasting (Including POS)

  For drugs in the clinical stage, peak sales are estimated based on current trial data, then multiplied by the probability of success for each indication (POS) to derive a risk-adjusted valuation. This approach facilitates cross-pipeline asset comparisons and sets realistic expectations.

• Industry/Industrial Analysis Framework

  Principles of Prudent Cross-Trial Comparisons

  In the absence of head-to-head trials, reports compare different trial datasets to assess relative advantages, but must clearly label “typical limitations of cross-trial comparisons,” reminding readers of potential biases arising from differences in baseline populations, control group selection, and follow-up durations.

Asset mapping & comparison

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

• BioNTech SE (BNTX.O)

  Rights holder for Pumitamig (in collaboration with BMY); the report deems it the optimal route to gaining exposure to the PD(L)1xVEGF bispecific antibody class

  Strengths

  Positive data from the global Phase II trial of Pumitamig, covering the entire population with high response rates

  Comparison

  The report explicitly states, ‘Within the scope of coverage, BNTX is the best way to gain exposure to this class of drugs’

  Risks

  Failure of Pumitamig’s global Phase III trial; setbacks in mRNA-based cancer vaccine pipelines

• Merck & Co., Inc. (MRK.N)

  Partner in the Sac-TMT program (with Kelun), also developing LM-299 (a PD-1xVEGF bispecific antibody)

  Strengths

  Positioned in both cutting-edge therapeutic areas; positive results from the Chinese Phase III Sac-TMT trial; receipt of an FDA Priority Review Voucher

  Weaknesses

  Sales forecast for Sac-TMT ($4.1 billion) falls short of market consensus ($5.4 billion)

  Risks

  Failure of Sac-TMT’s global trials; inadequate lifecycle management of Keytruda; delayed contributions from non-oncology pipelines

• Bristol Myers Squibb Co (BMY.N)

  Co-developer of Pumitamig

  Weaknesses

  The report assigns a UW (underweight) rating

  Risks

  Underperformance in new drug sales; clinical setbacks in pipeline assets; competitive products achieving success

• Pfizer Inc (PFE.N)

  Developer of PF'4404

  Strengths

  Positive Phase II data from PF'4404 in China, demonstrating strong responses and acceptable safety

  Weaknesses

  The report assigns an EW (neutral) rating

  Risks

  Weakening demand for COVID-related products; failure of combination vaccine development; existing products facing commercial challenges

Key data

• Sac-TMT plus Keytruda vs. Keytruda alone (OptiTROP-Lung05)Median PFS not reached vs. 5.7 monthsHR=0.28 (TPS 1–49%), 0.47 (TPS≥50%), p<0.0001
• Sac-TMT plus Keytruda ORR70.2%Vs. Keytruda monotherapy’s 42.0%
• Ivonescimab plus chemotherapy vs. Tevimbra plus chemotherapy (HARMONi-6)Median OS 27.9 vs. 23.7 monthsHR=0.66, but follow-up lasted only 21.4 months, and patients aged 65 and older saw no benefit (HR=0.93)
• Pumitamig (1400 mg) ORR (Rosetta-Lung02)73% in squamous cases, 64% in non-squamousGlobal Phase II, covering patients across all PD-L1 expression levels
• PF'4404 (10 mg) ORR and PFSORR 68%, median PFS 12.4 monthsChinese Phase II, effective across squamous/non-squamous and various PD-L1 subgroups

Impact & implications

If the global trial data for Sac-TMT and PD(L)1xVEGF bispecific antibodies are validated, they will reshape the first-line NSCLC treatment landscape and provide critical alternatives as Keytruda’s patent nears expiration in 2028. For companies: Merck benefits from its dual-pipeline strategy (Sac-TMT and LM-299), offering strategic flexibility; BioNTech, as a partner in the Pumitamig program, is identified by the report as the best way to gain exposure to this innovative class of drugs (OW rating); Shiyao Group/Kangfang Biotech’s Ivonescimab will need to rely on the credibility of the HARMONi-3 global data. Meanwhile, Sac-TMT has received an FDA Priority Review Voucher, potentially accelerating its U.S. regulatory timeline.

Risks

• Negative outcomes from the global Phase III trials of Sac-TMT and PD(L)1xVEGF bispecific antibodies (HARMONi-3, OptiTROP-Lung06)
• Competitive products (e.g., other TROP2 ADCs or bispecific antibodies) achieve breakthroughs in clinical or commercial terms
• Following Keytruda’s patent expiration in 2028, Merck fails to maintain market share through new drugs or effective lifecycle management
• Insufficient population representativeness in clinical data (e.g., by age or region) hinders global rollout

What to watch

• The OS and PFS data from the HARMONi-3 trial in the second half of 2026 (Ivonescimab vs. Keytruda plus chemotherapy)
• The global population results from the OptiTROP-Lung06 trial (Sac-TMT vs. Keytruda plus chemotherapy)
• The initiation and progress of the global Phase III trials for Pumitamig and PF'4404
• Updates on Sac-TMT’s clinical data in gynecologic malignancies and other cancer types