Adding the Immune Peptide Thymosin-α1 to Radiation and Immunotherapy Shrank Distant Tumors in Nearly 1 in 4 Patients

In this Phase II trial, combining hypofractionated radiotherapy with PD-1 inhibitor immunotherapy, GM-CSF, and the peptide thymosin-α1 achieved a 23.08% objective response rate and 65.38% disease control rate in heavily pretreated metastatic cancer patients. Median progression-free survival was 3.5 months. Notably, abscopal effects (tumor shrinkage at sites not directly irradiated) were observed in 23.08% of patients, with four achieving partial responses. Lower baseline neutrophil-to-lymphocyte ratio predicted better outcomes. The regimen was manageable with six grade 3-4 adverse events and no treatment-related deaths.

Multicenter Phase II trial enrolling patients with heavily treated metastatic solid tumors from September 2022 to May 2024. Treatment: HFRT to targeted tumors + GM-CSF for 14 days from day 1 + thymosin-α1 twice weekly until progression + camrelizumab (PD-1 inhibitor) every 3 weeks after HFRT. Endpoints included PFS, ORR, DCR, abscopal effects, and safety. Analysis by intention-to-treat.

Patients with heavily treated metastatic solid tumors have few remaining options. This trial demonstrates that adding the immunomodulatory peptide thymosin-α1 to a radiation-immunotherapy combination can produce meaningful responses including abscopal effects — where distant tumors shrink from local radiation combined with systemic immune activation. This suggests thymosin-α1 enhances the immune priming effect.

The combination of radiation with immunotherapy to generate systemic anti-cancer immune responses (the abscopal effect) has been a long-sought goal in oncology. Adding thymosin-α1 to this mix may enhance immune priming — the peptide has a long history as an immune modulator and is approved in several countries. This trial adds to growing evidence that peptide-based immune modulators can meaningfully augment cancer immunotherapy strategies.

Small sample size (37 patients) in a single-arm Phase II trial without a control group. Overall survival data not yet mature. Median follow-up of only 5.97 months is short. Cannot determine the individual contribution of thymosin-α1 versus the other components. Heterogeneous tumor types may complicate interpretation.