Hansoh’s HS-20093 met its Phase 3 goals, strengthening its status as a top B7-H3 ADC contender.
In less than a month, Hansoh Pharmaceutical‘s B7-H3 targeted antibody-drug conjugate (ADC) HS-20093 (Risvutatug Rezetecan) achieved two globally significant clinical breakthroughs.
On July 28, Hansoh announced that the ARTEMIS-011 Phase III osteosarcoma study met the primary endpoint of progression-free survival (PFS) as assessed by the Independent Review Committee (IRC). This is the world’s first B7-H3 ADC to achieve the primary endpoint of PFS in a Phase III osteosarcoma study, marking a milestone in the clinical validation of this target, which was once considered a “graveyard of research and development.”
Just recently, Hansoh announced that its Phase III registrational small cell lung cancer study ARTEMIS-008 had met its primary endpoint of overall survival (OS).
With successful results in two hard endpoints – small cell lung cancer and osteosarcoma – HS-20093 has become the only B7-H3-targeted ADC to date to report positive phase III study results in multiple tumors.
ADC drugs are hailed as “magic bullets” in the field of precision oncology, continuously reshaping the clinical treatment landscape of solid tumors with their innovative combination of targeted antibodies, linkers, and cytotoxic payloads. B7-H3, as a highly promising broad-spectrum anti-tumor target, is widely expressed in various malignant tumor tissues, but its expression level in normal human tissues is extremely low, presenting an ideal window for drug development.
Globally, many pharmaceutical companies are investing in the B7-H3 targeted ADC field, but for a long time, the clinical value of the target has lacked the highest level of evidence-based medicine support from Phase III clinical trials.
From a “graveyard of research and development” to a renewed clinical value, Hansoh Pharmaceutical’s HS-20093 has established a leading position in the global B7-H3 ADC field with solid Phase III data, a multi-tumor portfolio, and 11 breakthrough therapy designations, priority review qualifications, and orphan drug designations accumulated in China, the US, Europe, and Japan.
Historic breakthrough: Two Phase III hard endpoints achieved, solidifying the global leading position of B7-H3 ADCs
Small cell lung cancer (SCLC) is one of the most malignant subtypes of lung cancer, characterized by rapid disease progression and a high risk of relapse and drug resistance. The vast majority of patients experience rapid progression after first-line platinum-based chemotherapy, leaving second-line treatment options extremely limited. Topotecan has long been the standard treatment, but its efficacy has reached a significant plateau, offering limited improvement in patient survival and highlighting a substantial unmet clinical need. The pivotal Phase III ARTEMIS-008 study of HS-20093 in relapsed/refractory SCLC successfully met the primary endpoint of overall survival (OS) during the pre-specified period. Data showed that compared to the standard treatment of topotecan, HS-20093 provided patients with a statistically and clinically significant overall survival benefit, with consistent benefits observed in secondary endpoints such as progression-free survival (PFS). The drug’s safety profile remained consistent with previous studies, with no new safety risk signals identified.
This result is historic: ARTEMIS-008 became the world’s first Phase III clinical trial to demonstrate that B7-H3 ADCs can deliver significant overall survival (OS) benefits. For a long time, many B7-H3-targeted drug candidates worldwide have stalled in early clinical trials or only achieved tumor shrinkage, failing to translate anti-tumor activity into prolonged patient survival. Meanwhile, the positive OS result in the HS-20093 small cell lung cancer Phase III trial provides the first time, with the highest level of evidence-based validation, of the clinical drugability of the B7-H3 target, completely dispelling industry doubts about the target’s value and rebuilding global confidence in B7-H3 drug development.
Osteosarcoma is also a malignant tumor posing a significant clinical challenge, primarily affecting adolescents and included in China’s list of rare diseases. Patients with advanced, recurrent, or metastatic osteosarcoma have virtually no effective treatment options after failing multiple lines of chemotherapy, resulting in extremely poor prognosis. The pivotal Phase III clinical trial (ARTEMIS-011) of HS-20093, targeting patients who have progressed or relapsed after at least two lines of prior systemic therapy, successfully met the primary endpoint of IRC-PFS, demonstrating that the drug can effectively delay tumor progression and provide a new treatment option for adolescent patients suffering from this disease. Compared to chemotherapy, HS-20093 showed a statistically significant and clinically meaningful improvement in IRC-assessed PFS. Consistent benefits were also observed in secondary clinical endpoints (including overall survival (OS) and investigator-assessed PFS).
With the milestone breakthrough in overall survival (OS) of small cell lung cancer, HS-20093 has become the only B7-H3 ADC in the world to achieve positive key endpoints in two highly challenging phase III studies of solid tumors. Its dual-line clinical success has built a first-mover advantage that is difficult to catch up with.
Following the release of two significant Phase III top-line results, Hansoh Pharmaceutical will rapidly advance the preparation for the domestic new drug application of HS-20093, and simultaneously plans to release complete research data at an international academic conference. With the commercialization process nearing completion, HS-20093 is expected to quickly fill the treatment gaps in second-line treatment for small cell lung cancer and relapsed/refractory osteosarcoma, driving a revolution in the treatment paradigms for these two refractory tumors.
Multi-tumor synergistic development constructs a solid tumor treatment matrix
A breakthrough in a single indication can bring a product to market, while a multi-tumor indication strategy can maximize the value of a target and build a long-term competitive barrier. Leveraging the broad-spectrum expression of the B7-H3 target, Hansoh Pharmaceutical has developed a clear, tiered multi-tumor development roadmap for HS-20093, covering high-incidence and refractory solid tumors such as small cell lung cancer, osteosarcoma, non-small cell lung cancer, head and neck cancer, prostate cancer, esophageal squamous cell carcinoma, and colorectal cancer, forming a research and development pattern of “full-scale Phase III registration studies and multiple proof-of-concept studies.”
Currently, in the domestic R&D pipeline for HS-20093, four indications – small cell lung cancer, osteosarcoma, non-small cell lung cancer, and esophageal squamous cell carcinoma – have all entered the pivotal Phase III clinical trial stage. These four tumor types belong to the mainstream tracks of lung cancer, sarcoma, and gastrointestinal tumors, respectively, with a large patient base and urgent clinical needs. Among them, small cell lung cancer and osteosarcoma have already delivered positive topline data from Phase III trials; Phase III studies of non-small cell lung cancer and esophageal squamous cell carcinoma are progressing steadily, continuously accumulating evidence-based data, and are expected to further expand the drug’s applicable population in the future.
Meanwhile, the key proof-of-concept (PoC) clinical trials of HS-20093 for head and neck cancer, prostate cancer, and colorectal cancer are progressing rapidly. PoC studies aim to quickly validate the drug’s antitumor activity in the corresponding tumor types, explore optimal dosing regimens, and screen for high-potential patient populations. Once early studies confirm promising efficacy signals, Phase III registration trials for the relevant indications will be initiated quickly.
The tiered development strategy effectively balances R&D investment and development efficiency, prioritizing the rapid launch of mature indications while continuously exploring the potential value of targets and expanding product boundaries.
Looking at the global B7-H3 ADC competitive landscape, the vast majority of candidates focus on a single tumor type in clinical trials, with very few simultaneously advancing multiple Phase III pipelines. HS-20093’s multi-tumor-type parallel development model creates a distinct competitive advantage. As clinical data from different tumor types continues to be released, HS-20093 is expected to grow into a cross-cancer, platform-based precision medicine, covering a broad market from lung cancer and sarcoma to gastrointestinal tumors, genitourinary tumors, and head and neck tumors, fully unleashing the therapeutic potential of the B7-H3 target.
International and domestic clinical collaboration is leading global precision oncology treatment into a new stage.
Competition in the competitive landscape is constantly evolving, and first-mover advantage determines the long-term outcome.
Looking at the entire ADC industry, HS-20093 achieved two successful Phase III hard endpoints, bridging a crucial link in the transition of the B7-H3 target from basic research to clinical application, and providing an important reference for global drug development targeting the same target.
In December 2023, Hansoh and GSK entered into a strategic collaboration, granting GSK exclusive rights to develop, manufacture, and commercialize the product globally outside of Greater China. Leveraging GSK’s global clinical operations network, multiple clinical studies are being conducted simultaneously overseas, achieving synergistic collaboration between domestic and international clinical development.
On one hand, Hansoh s deeply involved in clinical practice in China and is rapidly advancing its domestic registration and launch; on the other hand, multinational pharmaceutical companies are leading global clinical development overseas, accelerating the delivery of their products to patients worldwide.
The dual-track development model, both domestically and internationally, coupled with the certification support from regulatory agencies in multiple countries, allows HS-20093 to transcend the limitations of a single market and possess the potential to become a first-in-class ADC drug globally.
In the wave of Chinese innovative drugs going global, HS-20093 not only exports original molecules, but also provides leading overseas clinical development strategies and target validation evidence, proving to the global oncology community that Chinese pharmaceutical companies have comprehensive strength in original innovation, cutting-edge target validation, and multi-center clinical development.
In the future, with the steady progress of new drug approval applications and the continued release of positive data from clinical studies across various tumor types, HS-20093 is expected to bring hope of survival to tens of thousands of patients with advanced solid tumors. In the era of Chinese innovative drugs going global, it will continue to drive global precision oncology treatment into a new stage.
Source: Hansoh Pharma | Top Image: Getty Images
