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

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

Evan S. Wu, MD, PhD

Evan S. Wu, MD, PhD

This article concludes a three-part series examining the translatability of Chinese clinical data into US regulatory pathways. The first article 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. The second article 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.1 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.2 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.3 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) 1A1.4 UGT1A1 polymorphisms may influence drug-induced toxicities of numerous medications used in oncology including irinotecan, belinostat, pazopanib (Votrient), or nilotinib (Tasigna). UGT1A1 genetic variants can affect enzymatic function, causing reduced metabolic capacity. In a meta-analysis by Nelson et al., the authors summarize the observed UGT1A1 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.5 HLX43 was evaluated in a FIH clinical study conducted entirely in China (NCT06115642).6 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.

References

  1. Shen J, Swift B, Mamelok R, Pine S, Sinclair J, Attar M. Design and conduct considerations for first-in-human trials. Clin Transl Sci. 2019;12(1):6-19. doi:10.1111/cts.12582
  2. Chen C, Lou N, Zheng X, Wang S, Chen H, Han X. Trends of phase I clinical trials of new drugs in mainland China over the past 10 years (2011-2020). Front Med (Lausanne). 2021;8:777698. doi:10.3389/fmed.2021.777698
  3. Dean L. Tamoxifen therapy and CYP2D6 genotype. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, eds. Medical Genetics Summaries. National Center for Biotechnology Information; 2014.
  4. Nelson RS, Seligson ND, Bottiglieri S, et al. UGT1A1 guided cancer therapy: review of the evidence and considerations for clinical implementation. Cancers (Basel). 2021;13(7):1566. doi:10.3390/cancers13071566
  5. Shan Y, Liu R, Song G, et al. Preclinical activity of HLX43, a PD-L1-targeting ADC, in multiple PD-1/PD-L1 refractory/resistant models. Ann Oncol. 2023;34(suppl 2):S483. doi:10.1016/j.annonc.2023.09.1879
  6. Wang J, Wan R, Zeng S, et al. A phase I clinical study to evaluate the safety, tolerability, and pharmacokinetic characteristics of HLX43 (anti-PD-L1 ADC) in patients with advanced/metastatic solid tumors. J Clin Oncol. 2025;43(suppl 16):3025. doi:10.1200/JCO.2025.43.16_suppl.3025

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