First Patient Dosed in Trial of HLX-4310 for Relapsed/Refractory Osteosarcoma

The first patient was treated with HLX-4310, an investigational oral combination of a class I selective histone deacetylase (HDAC) inhibitor and an mTOR inhibitor, in adolescents and adults with relapsed, refractory sarcoma, with a particular focus on osteosarcoma, according to a news release from Healx.

The phase 1/2 dose-escalation and dose-confirmation trial is being advanced in collaboration with the National Pediatric Cancer Foundation's (NPCF) Sunshine Project, a research consortium involving physicians and scientists from more than 30 pediatric cancer centers nationally.

“I’m excited to see this study begin dosing patients and to evaluate a strategy that is explicitly focused on preventing metastatic recurrence,” said Amy Armstrong, MD, principal investigator for the phase 1/2 HLX-4310 trial. “This trial will evaluate the safety and tolerability of HLX-4310 and assess efficacy, including its potential to reduce cancer recurrence risk.”

Rationale and Unmet Need

Osteosarcoma is a rare, aggressive bone cancer that most often affects children, adolescents, and young adults, and is the most common type of bone cancer in this population. Patients who develop metastatic disease face a 5-year survival rate of less than 30%, and survival outcomes for osteosarcoma have improved little over the past 40 years despite intensification of therapy, according to the company.² Metastasis, rather than the primary tumor, remains the most common cause of mortality even after successful control of primary tumors with surgery and chemotherapy.

According to Healx, HLX-4310 represents the first clinical proof point for the company's broader rare oncology strategy, which is focused on preventing metastatic recurrence rather than treating only overt tumors.¹ The scientific rationale behind the approach targets biological programs that Healx says enable micrometastatic tumors to survive and persist at distant sites before reemerging as metastatic disease. The company noted that because metastatic recurrence involves biological mechanisms shared across cancer types, therapies showing promise in osteosarcoma could plausibly be developed in parallel for other malignancies, including breast cancer, kidney cancer, and melanoma.

HLX-4310 is an oral combination of domatinostat (4SC-202), a class I-selective HDAC inhibitor, and sirolimus (rapamycin), an mTOR inhibitor. After screening of 3000 clinical-stage drugs using a phenotypic drug discovery platform, the combination was found to offer strong efficacy in osteosarcoma-specific pulmonary metastatic preclinical models, with the paired mechanisms of action intended to overcome resistance to targeted therapy.²

HLX-4310 combines 2 agents with complementary activity profiles: domatinostat is an investigational agent being evaluated for its epigenetic modulation of gene expression programs involved in tumor cell survival and tumor-immune interactions, whereas sirolimus is an FDA-approved mTOR inhibitor that targets a central pathway involved in cell growth, metabolism, and stress responses.

Trial Design and Drug Combination

The phase 1/2 trial is an open-label, cohort sequential dose-escalation and dose-confirmation study designed to evaluate the safety and efficacy of HLX-4310 in adolescents and adults with relapsed/refractory sarcoma and osteosarcoma. In phase 1, safety, tolerability, and pharmacokinetics will be evaluated in an intended 12 patients with relapsed/refractory sarcoma will receive escalating doses of domatinostat with a standard 2-mg dose of sirolimus. Patients aged 12 to 40 years are eligible; they must have undergone at least 1 line of standard-of-care systemic therapy and not be candidates for other therapies known to have survival advantages; those with central nervous system metastases are excluded.

Phase 2 is intended to include 2 arms of patients with osteosarcoma, one with resectable lung metastases and the other with unresectable lung metastases, with potential to also enroll a cohort of patients with other sarcomas. The primary end point will be event-free survival at 12 months in those who had resected metastases and at 4 months in those with unresectable metastases. Circulating tumor DNA will be evaluated and reported as an exploratory end point.

Investigator and Company Perspective

“Metastatic osteosarcoma is so difficult to treat because patients can undergo intensive therapy, reach remission, and still relapse within months or within several years,” said David Warshawsky, PhD, Healx's global head of metastatic prevention, in the announcement. “We believe that HLX-4310 provides a novel and differentiated approach focused on the unique biology hypothesized to drive cancer recurrence, and we are delighted to see it advance into trials.”¹

David Frazer, president of the National Pediatric Cancer Foundation, said the Sunshine Project consortium “brings together leading pediatric cancer centers to accelerate promising science into clinical studies,” and described the trial as reflecting the shared commitment of the Sunshine Project and Healx to drive progress for children and young adults facing high-risk cancers such as osteosarcoma.

REFERENCES

1. Healx Announces First Patient Dosed in Phase 1/2 Trial to Evaluate the Effect of HLX-4310 on Metastatic Recurrence and Progression in Sarcomas with a Focus on Osteosarcoma. News release. Healx. July 22, 2026. Accessed July 22, 2026. https://tinyurl.com/mww5r86t

2. Odri GA, Tchicaya-Bouanga J, Yoon DJY, Modrowski D. Metastatic progression of osteosarcomas: a review of current knowledge of environmental versus oncogenic drivers. Cancers (Basel). 2022;14(2):360. Published January 12, 2022. doi:10.3390/cancers14020360

3. Armstrong A. OsteoBites: Domatinostat/Sirolimus Sarcoma Trial (Relapsed/Refractory Phase 1/2). YouTube. September 26, 2026. Accessed July 22, 2026. https://www.youtube.com/watch?v=GMkSfv4sfbQ