Oncology Pipeline Update: Prostate Cancer T-Cell Engager Partnership, BTK Inhibitor Filing, and Novel Targeted Therapy Results
Key oncology developments include a $315 million partnership between Astellas and Vir for the prostate cancer T-cell engager VIR-5500, with updated phase 1 data showing an 82% PSA50 rate. The FDA accepted a filing for Ono Pharmaceuticals' tirabrutinib seeking accelerated approval in primary central nervous system lymphoma. Research findings also identified a new kidney cancer biomarker and showed promising results for the TRK inhibitor repotrectinib and the breast cancer triple therapy gedatolisib plus palbociclib and fulvestrant.
Several significant developments in cancer therapeutics were announced this week, including a $315 million partnership between Astellas and Vir for a prostate cancer T-cell engager, FDA acceptance of a filing for a new BTK inhibitor in central nervous system lymphoma, and multiple research findings on kidney cancer biomarkers and novel targeted therapies.
In a major deal for the prostate cancer pipeline, the Japanese group Astellas will pay $315 million up front to co-develop VIR-5500, a dual-masked PSMA-targeting T-cell engager from Vir. The deal includes $240 million in cash and $75 million in equity up front, plus a $20 million tech transfer milestone expected by mid-2027; total milestones could reach $1.37 billion. The companies will share development costs, with Astellas contributing 60% and Vir 40% globally; Vir has an option to co-promote the asset in the US, while Astellas will be solely responsible for commercialization outside the US. Updated phase 1 results for VIR-5500 in late-line metastatic castrate-resistant prostate cancer showed an 82% PSA50 rate among 17 prostate-specific antigen evaluable patients receiving at least 3,000µg/kg every three weeks. This compares with an earlier reported PSA50 rate of 58% among 12 patients receiving a first dose of 120µg/kg or higher. The updated results also showed a 53% PSA90 rate (9/17) and a 36% objective response rate (4/11). The safety profile included zero grade 3 or higher cytokine release syndrome cases at the ≥3,000µg/kg dose.
Meanwhile, the FDA has accepted a filing from Ono Pharmaceuticals seeking accelerated approval for tirabrutinib, a second-generation BTK inhibitor, in relapsed or refractory primary central nervous system lymphoma (PCNSL). The agency has set a December 18 action date. The application is based on data from the phase 2 Prospect trial, in which 48 patients with relapsed or refractory PCNSL treated with tirabrutinib monotherapy achieved a 67% response rate and a median progression-free survival of 6 months. Tirabrutinib has already been approved in Japan under the brand name Velexbru. A confirmatory head-to-head study is ongoing, pitting tirabrutinib against Rituxan and Temodar in PCNSL patients.
Additional research findings include a study identifying soluble MAdCAM-1 as a promising prognostic biomarker in metastatic kidney cancer. Researchers measured blood levels of soluble MAdCAM-1 in more than 1,000 patients and found that lower levels correlated with poorer prognosis: progression-free survival fell from 13.9 months in patients with high levels to 8.4 months in those with low levels. The findings suggest the biomarker could guide microbiota-targeted interventions to overcome treatment resistance.
In another development, the phase 1/2 TRIDENT-1 trial of the second-generation TRK inhibitor repotrectinib demonstrated promising efficacy in patients with NTRK gene fusion-positive solid tumours. Among patients who had never received a TRK inhibitor, nearly 6 out of 10 responded to treatment, with no disease progression for an average of more than two years. Among patients previously treated with a drug from the same class, nearly one in two also responded to repotrectinib. The treatment also proved effective against brain metastases.
Results from the phase III VIKTORIA-1 trial showed that the triple therapy of gedatolisib combined with palbociclib and fulvestrant significantly improved progression-free survival in patients with HER2-negative metastatic breast cancer. Patients who received the triple therapy achieved a progression-free survival of 9.3 months, compared with 7.4 months for those treated with gedatolisib and fulvestrant alone, and 2 months for those who received fulvestrant only.
Finally, the phase 2 ARROW study evaluated pralsetinib, a RET inhibitor, in RET fusion-positive non-small cell lung cancer. A total of 281 patients received the drug, with a response rate reaching 78% in treatment-naïve patients and 63% in those previously treated with chemotherapy. Median overall survival reached 44.3 months across all patients.