A phase 3 trial has linked GSK’s risvutatug rezetecan (ris-rez) to a 67% reduction in the risk of disease progression or death, providing evidence that B7-H3-directed antibody-drug conjugates (ADCs) work in relapsed osteosarcoma.
Hansoh Pharma, GSK’s Shanghai-based partner on the therapy, ran the phase 3 clinical trial in China. The study, Artemis-011, enrolled 122 patients aged 12 years and older who were failed by second-line treatments. Hansoh randomized participants to receive ris-rez or the chemotherapy combination of gemcitabine and docetaxel.
Median progression-free survival (PFS) was 5.5 months on ris-rez, compared to 1.5 months on chemotherapy. The difference amounted to a 67% risk reduction after a median follow-up of 7.1 months. Hansoh revealed the trial met its primary PFS endpoint in July without disclosing data.
GSK reported grade 3 or higher treatment-related adverse events (TRAEs) in 93% of patients receiving ris-rez at the 12 mg/kg dose and in 83% of those receiving chemotherapy. Hematologic events were the most common grade 3 or higher TRAEs in both arms. TRAEs led to discontinuation in 4% of patients on ris-rez and 2% of patients receiving chemotherapy. The results were consistent with earlier trials.
The data suggest B7-H3 ADCs improve outcomes in a setting that lacks approved drugs or a standard of care. Artemis-011 will extend randomized evidence on B7-H3 ADCs into osteosarcoma, H.C. Wainwright analysts said in a note to investors last month. The readout offers encouragement that B7-H3 ADCs work in the setting, while also setting the bar for other companies aiming to treat relapsed osteosarcoma.
Daiichi Sankyo and Merck & Co.’s ifinatamab deruxtecan (I-DXd) has led the way for B7-H3 ADCs in small cell lung cancer (SCLC), although regulatory setbacks, including the recent withdrawal of a filing for FDA approval, have closed the gap.
Osteosarcoma is on Daiichi and Merck’s roadmap, but I-DXd is trailing ris-rez in the setting. The partners started a global phase 1/2 clinical trial of I-DXd in July that, in its second part, will enroll patients with osteosarcoma and several other tumor types. GSK began a global phase 1/2 study of ris-rez in osteosarcoma and soft tissue sarcoma in June.
The rivals are running osteosarcoma trials alongside studies in other indications. As well as SCLC, B7-H3 ADC developers are targeting tumor types including esophageal cancer, non-small cell lung cancer and prostate cancer.
At the European Society for Medical Oncology Conference last week, GSK unveiled fresh data from its other Hansoh-partnered ADC. The presentation showed that among 45 patients with platinum-resistant ovarian cancer who received the B7-H4-directed mo-rez, there was a confirmed objective response rate of 62%, with a median duration of response of 12.2 months.
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