Evan S. Wu, MD, PhD, is an assistant professor at the University of Hawai’i Cancer Center

This article concludes a three-part series examining the translatability of Chinese clinical data into US regulatory pathways. 

 explored bridging studies, which are abbreviated studies designed to assess whether clinical trial data generated outside the United States can be considered applicable to the US population. 

 focused on how clinical end points selected in bridging studies can affect their regulatory acceptability, particularly in the context of oncology drug development. In this final installment, we address an increasingly relevant question: Can first-in-human (FIH) data generated solely in China support and accelerate oncology drug development programs in the United States?

FIH data from China offers the potential to expedite US clinical development programs by enabling early-phase dose expansion or phase 2 trials without redundant phase 1 trials performed in the US. In traditional drug development models, FIH studies aim to translate safety and pharmacology insights from preclinical animal models into humans.

 However, the growing sophistication of global clinical research infrastructure in China and rapidity at which they complete FIH studies opens a new pathway for US oncology drug development: using robust China-only FIH data to directly initiate a phase 1b or phase 2 clinical trial.

This accelerated pathway to US drug development brings us back to a central theme explored in the first article of this series – the redefinition of “translatability.” Historically, translatability referred to the leap from animal models to humans. Today, it also encompasses the ability to transfer human clinical data across regulatory jurisdictions and diverse patient populations. The potential benefits of leveraging China-only FIH data are considerable. Clinical trials in China often offer faster and more cost-effective patient recruitment than comparable studies conducted in the US, allowing early-stage programs to gain critical human data quickly and efficiently.

 From a business standpoint, investors are much more likely to financially support an emerging oncology drug if it has positive FIH data as compared to one with only preclinical data.

A fundamental concern, however, is whether racial and ethnic differences in drug metabolism could limit the relevance of China-only data to a more diverse U.S. population. Genetic polymorphisms that affect drug-metabolizing enzymes, transporters, and molecular targets can influence pharmacokinetics and pharmacodynamics, raising questions about the generalizability of early-phase data. For instance, tamoxifen is metabolized into its active form by cytochrome P450 enzymes.

 Variants of the CYP2D6 enzyme are distributed differently across populations. Approximately 6% to 10% of European Caucasians are poor metabolizers. Compared with Europeans, individuals of Asian descent are more likely to be intermediate metabolizers and ultra-rapid metabolizers are particularly prevalent among North Africans and Ethiopians.

Another example of differences in racial/ethnic metabolism is with the enzyme uridine diphosphate glucuronosyltransferase (UGT) 1A1.

 polymorphisms may influence drug-induced toxicities of numerous medications used in oncology including irinotecan, belinostat, pazopanib (Votrient), or nilotinib (Tasigna). 

 genetic variants can affect enzymatic function, causing reduced metabolic capacity. In a meta-analysis by Nelson et al., the authors summarize the observed 

 polymorphisms by racial/ethnic ancestry and how these polymorphisms may affect metabolism of different oncology drugs.

These well-documented examples illustrate the biological rationale for adjusting doses and monitoring safety closely when applying China-only data to US trials. Nonetheless, it is important to maintain perspective. The polymorphisms involved, while clinically meaningful, are relatively rare in the broader population. Additionally, the US itself is an ethnically heterogeneous country, making the application of subgroup-specific adjustments part of routine clinical trial design. While the complexity of pharmacokinetics and pharmacodynamics for new oncology agents cannot be overstated, having human data, regardless of country of origin, offers a significant head start. Importantly, human safety and efficacy signals translate more reliably across racial/ethnic borders than preclinical animal data do. This raises the critical regulatory question: Is China-only FIH data sufficient for the FDA to permit a global phase 1b or phase 2 trial including US patients? There are growing signs that the answer is yes, provided the data package is robust and scientifically sound.

One compelling example of this approach comes from the Chinese pharmaceutical company Henlius, which is developing HLX43, an anti–PD-L1 antibody-drug conjugate (ADC). This compound is engineered with a highly potent topoisomerase I inhibitor payload known for its prolonged bystander killing effects.

 HLX43 was evaluated in a FIH clinical study conducted entirely in China (NCT06115642).

 The study was divided into two parts. Part 1 evaluated escalating doses (0.5, 1, 2, 3, and 4 mg/kg administered every three weeks) in patients with advanced solid tumors. Part 2 focused on non–small cell lung cancer (NSCLC), assessing HLX43 at doses of 2, 2.5, and 3 mg/kg.

The results from part 1 were promising. Among 18 patients, including 12 with NSCLC and others with head and neck, cervical, thymic, nasopharyngeal, uterine, and small cell lung cancers, treatment-emergent adverse effects (TEAEs) occurred in all participants, but the majority were limited to grade 1 or 2 severity. Only one patient in the highest dose group (4 mg/kg) experienced a dose-limiting toxicity (DLT), consisting of febrile neutropenia and decreased white blood cell count. The investigator-assessed objective response rate (ORR) was 31.3% (95% CI, 11.0%-58.7%).

In part 2, 21 patients with NSCLC were treated with a 2-mg/kg dose of HLX43. The ORR was 38.1% (95% CI, 18.1%-61.6%), and the disease control rate reached 81.0% (95% CI, 58.1%-94.6%). Eight patients achieved partial responses. While all patients experienced TEAEs, most were of low grade, and only seven (33.3%) patients had grade 3 or higher events. The overall tolerability and observed efficacy in this population, which had previously failed standard therapies, were viewed as highly encouraging. Based on the strength of these China-only FIH results, Henlius initiated a global phase 2 study (HLX43-NSCLC201; NCT06907615) to further evaluate HLX43 in patients with advanced NSCLC. Notably, this trial includes clinical sites in the United States. The fact that a global phase 2 program was approved without prior US phase 1 data underscores the regulatory viability of using China-only FIH data to accelerate oncology drug development in the US.

This case marks an important shift in global drug development strategy. It demonstrates that with rigorous data and well-designed studies, early-phase human data from China can support expedited entry into US clinical trials. It also reflects an evolving regulatory mindset, one that increasingly emphasizes the quality of the data rather than its geographic origin. Pharmacokinetic and pharmacodynamic variability due to racial and ethnic differences, though important, are generally manageable in the context of modern oncology drug development. In the HLX43 case, robust China-only phase 1 data demonstrating tolerability and preliminary efficacy supported initiation of a global phase 2 study.

For global biopharmaceutical companies, the strategic implications are profound. A China-first development strategy can serve as a path for accelerated entry into the US market. This model is especially relevant in oncology, where time is a critical factor for both patients and drug developers. Utilizing robust China-only FIH data can reduce the need for duplicative trials, lower development costs, and shorten the timeline for getting promising new therapies to US patients.

In conclusion, globalization is no longer a future goal but a current necessity in oncology drug development. As the field becomes increasingly competitive, the ability to integrate ex-US data into US regulatory submissions is a major advantage. The Henlius HLX43 case illustrates how China-only FIH data, when supported by high-quality trial design and clear clinical benefit, can provide a direct route to later-phase trials in the US. This approach represents a fundamental change in how we think about early-phase oncology drug development. By embracing high-quality international data, we not only accelerate innovation but also expand access to potentially life-saving therapies for patients worldwide.

Evan S. Wu, MD PhD, is an assistant professor at the University of Hawai’i Cancer Center in Honolulu.

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Articles

Evan S. Wu, Md, PhD, concludes a three-part series highlighting the translatability of Chinese clinical data into US regulatory pathways.

Accelerating US Oncology Drug Development Using Chinese First-in-Human Data

 on the translatability of Chinese drug development data to US regulatory standards, we discussed bridging studies, which are clinical trials designed to assess whether data generated outside the US can be considered applicable to a US population. These studies typically feature a condensed trial design incorporating patients in the US to confirm the efficacy and safety of an investigational therapy within the US health care and demographic context.

This second article delves into one of the most pivotal aspects of designing a successful bridging study: the selection of clinical end points. Specifically, we explore end point selection as it relates to regulatory acceptability in oncology drug development. As drug developers strive to bring promising therapies to market, the choice of end point can accelerate or, in some cases, delay approval.

survival (OS) remains the gold standard for demonstrating clinical benefit in oncology clinical trials.

 However, OS is also the clinical end point that takes the longest time to mature and can extend drug development timelines significantly.

 In scenarios where a robust phase 3 trial has already demonstrated an OS advantage, such as in a China-only study, the question becomes whether those data can be leveraged to develop an expedited US bridging study. If so, what additional data are needed from a US cohort to satisfy the FDA’s evidentiary standards?

From a regulatory perspective, bridging studies are not meant to repeat the large registrational study, but instead, investigators use them to confirm consistency of efficacy and safety in a representative US population. This opens the door to consideration of alternative end points apart from OS, such as progression-free survival (PFS)and objective response rate (ORR). Although PFS is widely accepted as a surrogate end point in oncology trials, its use in bridging studies presents unique challenges, particularly due to the constancy assumption.

This assumption assumes that the treatment effect remains stable over time. In other words, PFS HRs assume that the treatment effect between the intervention and control groups are the same at 3 months, 6 months, 12 months, and the end of the study.

 This assumption can be problematic in many oncology trials involving immunotherapy or targeted therapies, where PFS curves often exhibit delayed separation or varying slopes over time. Additionally, PFS can be confounded by differences in imaging schedules, assessment frequency, and clinical practice patterns.

 These limitations make interim PFS analyses potentially unreliable and challenge the interpretability of short-term data from small US bridging cohorts.

In contrast, ORR provides a more immediate, binary assessment of tumor response, typically based on RECIST criteria.

 ORR is not dependent on time-to-event analyses and can be evaluated early, making it well-suited for use in abbreviated bridging studies, especially when prior larger registrational trials have already demonstrated durable PFS and OS benefits.

 Although ORR alone is generally insufficient for regulatory approval, in the context of bridging studies where comprehensive efficacy data already exist, it may provide additional safety and efficacy data in a US population to show global consistency leading to FDA approval.

A recent example of this approach involves SAF-189s, a next-generation ALK/ROS1 inhibitor developed by Fosun Pharma/Henlius Biotech.

 SAF-189s had already demonstrated robust efficacy in the randomized phase 3 REMARK trial (NCT06569420) conducted in China, significantly prolonging PFS (HR, 0.23, 

 < .0001) and reducing the risk of central nervous system progression by 96% compared with crizotinib (Xalkori) in treatment-naive patients with ALK-positive NSCLC. The trial also showed a compelling OS signal.

I was approached by Fosun/Henlius to assist in developing a US bridging study. The sponsor initially proposed PFS as the primary end point. However, in discussions with the FDA, concerns were raised about the validity of early interim PFS data, given the statistical challenges related to the constancy assumption. The FDA allowed ORR to serve as the primary end point for the bridging study based on the robust data from the REMARK trial (ORR, PFS, OS, safety) and recognition that interim PFS analyses could be misleading due to time-dependent variability. The ORR data from a proposed US cohort in a future study, in combination with OS and PFS results from the REMARK trial,

 were deemed sufficient to demonstrate consistency of efficacy and safety. By allowing ORR to serve as the pivotal end point, the FDA demonstrated flexibility and scientific pragmatism in its regulatory decision-making, underscoring different strategies for global oncology drug development.

The SAF-189s case highlights the ever-changing landscape in global drug development. In bridging studies, especially those involving highly active anticancer therapeutics with clear OS signals outside the US, using a short-term end point such as ORR can: (1) reduce the time needed to generate confirmatory data in the US by leveraging clinical data from outside the US, and (2) avoid statistical pitfalls associated with early PFS readouts.

In conclusion, bridging studies are an increasingly common strategy for global oncology drug development, especially for Chinese sponsors seeking US market entry. End point selection in these studies is not merely a technical decision: It is a clinical and regulatory strategy that can influence timelines, approval pathways, and patient access. As demonstrated in the SAF-189s experience, a thoughtful approach that pairs robust foreign data with a clinically meaningful, efficient US end point can satisfy regulatory requirements while expediting development. The FDA is open to end point innovation, particularly when paired with data from large clinical trials outside the US.

In the third and final installment of this series, we’ll explore operational execution in China-to-US bridging studies, including site selection, cultural barriers, and timelines to ensure successful trial delivery.

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Bridging studies are crucial for translating Chinese drug development data to meet US regulatory standards, particularly in oncology. The selection of clinical endpoints, such as overall survival (OS), progression-free survival (PFS), and objective response rate (ORR), plays a pivotal role in these studies. While OS is the gold standard, it can delay timelines. ORR offers a quicker assessment and can be pivotal in bridging studies when robust foreign data exists. The SAF-189s case exemplifies how strategic endpoint selection can expedite US market entry, highlighting the FDA's openness to endpoint innovation.

Evan S. Wu, MD, PhD, delves into the one of the most pivotal aspects of designing a successful bridging study: the selection of clinical end points.

Choosing Clinical End Points in China for US Bridging Studies

Translational researchers in drug development focus on advancing new therapeutics based on preclinical laboratory findings using animal models. This lengthy and costly process often spans several years before a drug candidate progresses from preclinical to first-in-human studies. Enter China. The recent tsunami of drug candidates successfully trialed in humans in China at a blistering pace is creating a new definition of translational research in the United States, one where clinician-scientists are translating early-phase data from China to a US population.

In this 3-part monthly series, I will explore key (and controversial) issues surrounding the translatability of Chinese drug development data to a US population, including the novel concept of bridging studies, the selection of end points in China-to-US translational studies, and racial/ethnic differences in drug metabolism.

In 2024, China accounted for an astonishing 23% of global drug candidates, second only to the United States.

 The number of oncology drugs developed in China has steadily risen since the launch of the “Made in China 2025” strategic plan in May 2015, with record levels being reported in 2024 and even higher numbers forecasted for 2025.

 This initiative aimed to position China as a global manufacturing leader, targeting the industrialization of 20 to 30 innovative drugs by 2025. As of March 2025, the Chinese initiative has well superseded its goal. The success of Chinese drug developers can be attributed to their ability to move rapidly and at a lower cost compared with US counterparts due to competitive advantages in staffing and supply chains.

 Biotech start-ups in China can go from launch to first-in-human data reporting in 18 months or less, compared with a few years in the US.

However, nothing in life is without controversy, and the question of transcontinental applicability looms large. The FDA has historically rejected China-developed cancer drugs when they have been trialed exclusively in China. Geopolitical considerations aside, previous research has shown that racial and ethnic differences can affect the maximum tolerated dose (MTD) in phase 1 clinical trials. For example, studies conducted in Japan have shown differences in MTD for cytotoxic and targeted anticancer drugs between Japanese and Western populations, attributed to both intrinsic and extrinsic ethnic factors.

How do we bridge the gap? The innovative concept of bridging studies plays a crucial role in demonstrating the translatability of China-only early-phase clinical trials to a Western population.

 With an increasing share of new drugs originating in China, bridging studies are becoming an integral part of US drug development. Although the goal of oncology drug development is to improve the quantity and quality of life for patients with cancer, the reality is that biotech firms face immense pressure to bring drugs to market as swiftly and efficiently as possible. Bridging studies accelerate global drug approval by supplementing existing data with region-specific findings. Successful bridging studies that prove translatability from China to the US must enroll a diverse US population including Black and Hispanic patients, show pharmacokinetic (PK) and pharmacodynamic similarities across racial/ethnic groups, and confirm that efficacy and safety align with those observed in the original study. These elements are crucial for a bridging study to achieve the ultimate goal of a successful biologics license application with the FDA.

As coprincipal investigator of the Henlius-sponsored, phase 3 ASTRIDE clinical trial (NCT05468489) for small cell lung cancer (SCLC), I have had firsthand experience with the complexities of bridging studies. The ASTRIDE trial seeks to demonstrate the applicability of data from the global but China-majority phase 3 registrational ASTRUM studies to a US-only population. ASTRUM-004 (NCT04033354) and ASTRUM-005 (NCT04063163) successfully established that the PD-1 inhibitor serplulimab, in combination with chemotherapy, improved overall survival (OS) and progression-free survival in patients with advanced squamous non–small cell lung cancer and extensive-stage SCLC, respectively, compared with chemotherapy alone.

 Despite the inclusion of 31% White patients from Europe in ASTRUM-005,

 the FDA raised concerns due to the absence of US participants and the lack of representation from Black and Hispanic populations in the registrational study. In response, the FDA recommended that Henlius collect additional data to demonstrate the relevance of ASTRUM’s findings to US patients. After careful deliberation and design consideration, the ASTRIDE bridging study was conceived. This 2-arm descriptive study would enroll 100 patients per arm, with one group receiving serplulimab plus chemotherapy and the other receiving atezolizumab (Tecentriq) plus chemotherapy.

The success of bridging studies such as ASTRIDE depends on leveraging previously reported clinical trial data. The FDA approved the descriptive study design for ASTRIDE, rather than a superiority study, because the global ASTRUM trials had already validated the efficacy and safety of serplulimab plus chemotherapy in a large, non-US cohort. The primary objective of ASTRIDE is to confirm the applicability of ASTRUM’s findings to the US patient population by demonstrating similar safety, efficacy, and PK data, without the aim of proving statistical superiority or noninferiority. Although the concept of a descriptive bridging study may seem unconventional to clinical trial purists, the rapid pace of Chinese drug development and the FDA’s commitment to providing the US population with the most effective therapies available globally serve as motivating drivers for this flexible study design.

In the next article, I will examine the challenges associated with clinical end point selection and trial design in bridging studies, particularly in cases where preexisting data are limited to Chinese patients or when OS is not a logistically feasible end point for cancers with a favorable prognosis. I will explore the most efficient strategies for translating data from China to the US in these more complex scenarios.

Evan S. Wu, MD, PhD, is an assistant professor at the University of Hawai’i Cancer Center.

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China's rapid drug development, particularly in oncology, is reshaping translational research by providing early-phase data for US populations. Bridging studies are crucial for translating Chinese clinical trial data to the US, addressing racial and ethnic differences in drug metabolism. The ASTRIDE trial exemplifies this approach, aiming to validate the applicability of Chinese data to US patients. Despite challenges, such as FDA concerns over diverse representation, bridging studies offer a pathway to accelerate global drug approval, ensuring effective therapies reach diverse populations efficiently.

In a 3-part series, Evan S. Wu, MD, PhD, will explore key issues surrounding the translatability of Chinese drug development data to a US population.

Evan S. Wu, MD, PhD

Articles

Accelerating US Oncology Drug Development Using Chinese First-in-Human Data

Choosing Clinical End Points in China for US Bridging Studies

Redefining Translational Research and China’s Impact on US Drug Development