Akeso has once again captured the world's attention.

 

On the evening of May 31, Akeso announced that its Phase III HARMONi-6 study of ivonescimab (PD-1/VEGF bispecific antibody) plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (sq-NSCLC) achieved positive overall survival (OS) results.

 

The study was selected for the Plenary Session of this year's American Society of Clinical Oncology (ASCO) Annual Meeting and presented as a Late-Breaking Abstract (LBA). The Plenary Session is the most prestigious and influential segment of the ASCO meeting, typically reserved for findings deemed to have a transformative impact on oncology research and clinical practice.

 

HARMONi-6 is the only Chinese project selected for this session this year.

 

Data showed that in the intent-to-treat (ITT) population, ivonescimab plus chemotherapy significantly reduced the risk of death by 34% compared to the control group, with a hazard ratio (HR) of 0.66 (95% CI: 0.50–0.87), P=0.0017 (below the prespecified threshold of 0.0049). Median overall survival (mOS) was 27.9 months in the treatment group versus 23.7 months in the control group. The treatment group's mOS was calculated following a steep drop in the Kaplan-Meier curve to the median point due to the last death event in that group.

 

In a previously scheduled interim analysis of progression-free survival (PFS), ivonescimab plus chemotherapy had already demonstrated clinically meaningful and statistically significant positive results compared to tislelizumab plus chemotherapy, with median PFS (mPFS) of 11.1 months versus 6.9 months (HR=0.60, 95% CI: 0.46–0.78, P<0.0001).

 

This data is not only a victory for Akeso but also a milestone symbolizing Chinese innovation driving the advancement of global oncology treatment. With robust Phase III "head-to-head" data, ivonescimab has redefined the first-line treatment standard for sq-NSCLC, establishing a new benchmark for clinical benefit and heralding the end of the PD-1 inhibitor "dynasty era."

 

But the story does not end here. At this year's ASCO Annual Meeting, a series of major advances in first-line non-small cell lung cancer (NSCLC) treatment were unveiled, revealing an even more intense competitive landscape. Will Keytruda become the former king? And who will be the new king?

 

TONACEA 01: Ivonescimab's Accession Awaits Only the Right Conditions

 

First-line NSCLC treatment is Keytruda's absolute core territory.

 

According to a Mordor Intelligence research report, the global NSCLC market reached US$21.98 billion in 2025 and is expected to grow to US$24.17 billion in 2026. PD-1/PD-L1 inhibitors are estimated to account for 40.85% of the NSCLC market in 2025, while ADCs represent the fastest-growing category, with a compound annual growth rate of 11.74%.

 

In 2017, Keytruda was approved as a first-line therapy for NSCLC, and its sales began to accelerate. In the second quarter of 2018, Keytruda overtook Opdivo for the first time; that same year, Opdivo announced its failure to challenge Keytruda for first-line NSCLC. Since then, Opdivo has never been able to compete with Keytruda. In 2025, Keytruda's annual sales exceeded US$31.6 billion, while Opdivo's global sales were approximately US$10 billion, less than one-third of Keytruda's.

 

As the cancer with the largest patient population, the NSCLC space has never lacked latecomers. The current cohort of challengers is particularly strong, forming two distinct strategic fronts: the PD-(L)1/VEGF bispecific antibody front and the IO+ADC front. Both fronts were clearly evident at this year's ASCO.

 

Akeso's ivonescimab is the pioneer of the PD-(L)1/VEGF front.

 

As early as 2024, in the HARMONi-2 study directly comparing ivonescimab to Keytruda as first-line treatment for PD-L1-positive NSCLC patients, the ivonescimab group achieved a median PFS of 11.1 months, significantly superior to the Keytruda group's 5.8 months, representing a 49% reduction in the risk of disease progression or death. This made ivonescimab an instant sensation.

 

The HARMONi-6 study data now further demonstrates ivonescimab's strength. However, the biggest remaining question and expectation is whether this PD-1/VEGF bispecific antibody can enter the US market and directly compete with Keytruda on the commercial battlefield.

 

HARMONi-6 is a China-based study. The ultimate outcome of the FDA review will depend on whether the results of the global multi-regional Phase III HARMONi study can convince the FDA.

 

In January of this year, based on the HARMONi study results, Summit Therapeutics, Akeso's overseas partner, announced that it had submitted a marketing application to the FDA for ivonescimab in combination with chemotherapy for EGFR-mutant NSCLC patients who have progressed following EGFR TKI therapy.

 

In September 2025, Summit disclosed updated results from the HARMONi study at the 2025 World Conference on Lung Cancer. After extending the median follow-up time to 13.7 months, the data maturity for the Western patient cohort increased, and the OS HR improved to 0.78 (p=0.0332). Compared to the data announced in May of that year, the OS benefit had improved, but still did not reach the study's prespecified statistical significance threshold (p≤0.0448). For PFS, the ivonescimab group significantly reduced the risk of disease progression or death by 48% (HR=0.52, p<0.00001), meeting the study's primary endpoint.

 

While opinions differ on the 2025 data results, the fact that the FDA accepted the BLA application itself suggests that ivonescimab's data still holds promise.

 

However, the path forward is not without obstacles. In early May, Summit disclosed interim analysis results from the global pivotal Phase III HARMONi-3 study: the squamous cell carcinoma cohort for first-line treatment of metastatic NSCLC did not meet the prespecified statistical significance threshold for PFS at the interim analysis. The Independent Data Monitoring Committee recommended that the study continue as planned, with final data expected in the second half of 2026.

 

These setbacks have not deterred competitors. On the ASCO floor, numerous other Chinese innovative drug achievements are vying for a seat at the first-line NSCLC treatment table.

 

TONACEA 02: Continued Betting on PD-(L)1/VEGF Bispecifics

 

The success of ivonescimab ignited a BD boom in the PD-(L)1/VEGF bispecific field.

 

In 2024, BioNTech wholly acquired Biotheus for an upfront payment of US$800 million plus up to US$150 million in milestones, gaining full rights to its PD-L1×VEGF-A bispecific antibody PM8002 (BNT327, pumitamig). The following year, BioNTech entered into an agreement with BMS to co-develop pumitamig, with total deal consideration reaching as high as US$11.1 billion.

In May 2025, Pfizer and 3SBio reached an agreement under which Pfizer acquired exclusive rights to develop, manufacture, and commercialize PF-08634404 (SSGJ-707) outside mainland China for an upfront payment of US$1.25 billion, milestone payments of up to US$4.8 billion, and tiered royalties. Pfizer also retains an option to acquire commercialization rights in mainland China with an additional payment. This transaction not only set a new record for upfront payments in Chinese innovative drug out-licensing but also set a new record for total single-asset deal value.

 

Both of these PD-(L)1/VEGF bispecific antibodies, originating from China, presented key data on NSCLC-related indications at this year's ASCO.

 

BioNTech, in a rapid oral presentation, disclosed interim Phase II data from the global Phase II/III ROSETTA Lung-02 clinical trial of pumitamig. As of April 13, 2026, among 40 evaluable patients with a median follow-up of 9 months, pumitamig plus chemotherapy showed a confirmed objective response rate (cORR) of 57.1% in non-squamous NSCLC patients and 68.4% in squamous NSCLC patients, with a disease control rate (DCR) of 100%.

 

Good anti-tumor activity was observed at both dose levels, with higher response rates in the lower dose group: cORR of 63.6% in non-squamous patients and 72.7% in squamous patients. More notably, efficacy was robust across PD-L1 expression levels: 47.6% in the tumor proportion score (TPS) <1% group, 77.8% in the TPS 1%-49% group, and 100% in the TPS ≥50% group.

 

Pfizer's PF-08634404, based on early Chinese study data, showed a cORR of 67.6% as monotherapy in first-line PD-L1-positive NSCLC, including 75% in squamous cell carcinoma patients and 63.6% in non-squamous cell carcinoma patients.

 

However, there is a divergence in clinical endpoint design between BioNTech/BMS and Pfizer.

 

The Phase III part of ROSETTA Lung-02 will evaluate the efficacy of pumitamig plus chemotherapy versus Keytruda plus chemotherapy, with the primary endpoint being PFS assessed by blinded independent central review (BICR). Key secondary endpoints include OS, ORR, and duration of response (DOR).

 

Pfizer, on the other hand, insists on OS as at least one of the primary endpoints for all its Phase III trials of PF-08634404, including the Symbiotic-Lung-01 trial for first-line NSCLC. This aligns with the strategy adopted by Summit in its Phase III trials of ivonescimab and by Merck in its Keytruda trials.

 

The logic behind pumitamig's design is that allocating the full alpha significance level to the PFS analysis allows for the earliest possible readout. PFS is an established, early, sensitive, and acceptable endpoint for Phase III studies of such compounds. With a PFS readout, there is an opportunity to sit down with regulators. At the same time, OS remains a key secondary endpoint in the FDA's review package.

 

But Pfizer takes a different view. Johanna Bendell, Pfizer's Chief Development Officer for Oncology, stated clearly at ASCO that Pfizer is fully aware of BioNTech and BMS's approach but remains committed to OS as a co-primary endpoint. "We still think OS is very important, not only for patient impact and understanding the drug's effect, but also from a regulatory standpoint. It's critical to show OS benefit."

 

Dr. David Spigel, President and Chief Medical Officer of the Sarah Cannon Research Institute and an ASCO lung cancer expert, also noted that in lung cancer, statistically significant OS is very important because it enhances physician confidence that a PFS benefit is truly meaningful.

 

"When OS is a secondary endpoint, is its scientific reliability comparable to when it is a primary endpoint? I don't think so. However, the difference may be very small and still clinically significant. For first-line NSCLC treatment, PFS alone may not be sufficient for US regulators unless it is combined with something else, like a secondary OS endpoint or a quality-of-life endpoint, to address an unmet medical need," he said.

 

TONACEA 03: Two Routes, Same Bullseye

 

As challengers warm up, Merck is not standing idly by.

 

Keytruda's core patent is set to expire in 2028. To extend the lifecycle of this mega-blockbuster, Merck is exploring every possible avenue. Among them, the combination with sacituzumab tirumotecan (Sac-TMT) is one of its core strategies.

 

In May 2022, Kelun-Biotech and Merck entered into a collaboration agreement, granting Merck exclusive rights to develop, manufacture, and commercialize Sac-TMT outside Greater China, with a total deal value of nearly US$1.4 billion.

 

To date, Merck has initiated 17 Phase III clinical trial programs for Sac-TMT across various tumor types, underscoring the high priority it places on the asset.

 

On May 31, results from the Phase III clinical study OptiTROP-Lung05 of Sac-TMT plus Keytruda as first-line treatment for PD-L1-positive NSCLC were announced and concurrently selected for an oral presentation at the 2026 ASCO Annual Meeting.

 

Interim analysis results showed that compared to Keytruda alone, the combination therapy significantly prolonged PFS and reduced the risk of disease progression or death, with an HR of 0.35. Consistent PFS benefits were observed across prespecified subgroups, including PD-L1 expression levels and histology subtypes. The PFS HR was 0.47 for the PD-L1 TPS ≥50% subgroup and 0.28 for the TPS 1%-49% subgroup; the PFS HR was 0.28 for non-squamous and 0.44 for squamous histology. A positive trend in OS was also observed, with an HR of 0.55.

 

Of course, Merck is not alone in betting on the IO+ADC route. AstraZeneca/Daiichi Sankyo's TROP2 ADC Datroway (Dato-DXd) is also being explored in combination with Keytruda in NSCLC.

 

The TROPION-Lung02 study evaluated the efficacy and safety of Dato-DXd plus Keytruda with or without platinum-based chemotherapy as first-line treatment for advanced NSCLC patients. Results showed a cORR of 54.8% and mPFS of 11.2 months in the dual combination group (Dato-DXd + Keytruda), and a cORR of 55.6% and mPFS of 6.8 months in the triple combination group (Dato-DXd + Keytruda + platinum).

 

This is a multi-hundred-billion-dollar global competition. The PD-(L)1/VEGF bispecific and IO+ADC routes are advancing in parallel. But no matter which route ultimately prevails, one fact cannot be overlooked.

 

That is, in this contest to shape the future of first-line lung cancer treatment, Chinese innovative drugs are no longer supporting players. From Akeso, to Kelun-Biotech, to 3SBio, Chinese pharmaceutical companies are participating in, and even leading, the reshaping of core treatment standards with robust data. This is not an isolated high moment for a local biotech; it is the beginning of a new era for a major power in pharmaceuticals.

 

This momentum will culminate in a concentrated release in Shanghai this July.

 

From July 22 to 24, 2026, the inaugural "Great Power New Drugs" Global Conference, hosted by TONACEA, will be held at the National Exhibition and Convention Center (Shanghai). Benchmarking the J.P. Morgan Healthcare Conference, the conference adopts the core model of "Chinese Innovation – Global Translation – Shanghai Transaction," bringing together multinational pharmaceutical companies, top investment institutions, regulatory experts, and research pioneers, covering the full chain of R&D, clinical development, BD, investment and financing, and globalization.

 

This is a collective debut of China's new drugs moving from "participation" to "leadership," and it is the strongest message China's new drugs can send to the world.

References:

 

• In next-gen IO race in NSCLC, BioNTech/BMS and Pfizer are divided on overall survival approach; FiercePharma

• At ASCO, Merck makes case for a 'cornerstone' cancer drug; BioPharma Dive

• An innovative drug leader rapidly transitioning from liver disease to oncology; Southwest Securities

• PD-1/VEGF: The track has gone "over the top" – where is the next BD opportunity?

• Data improves, but Akeso falters?

• Ivonescimab's mid-course "waves"