Several new agents designed to reactivate the immune system were tested in combination with FDA-approved immunotherapies, as reported in data presented at the annual meeting of the American Society of Clinical Oncology. All new agents are potential neoadjuvant therapies (given before other treatments or surgery), and results have come from Phase 2 clinical trials.

Cobolimab, a new immunotherapy agent, was tested in patients with high-risk, resectable Stage IIB-IVA melanoma in combination with the drug dostarlimab, an FDA-approved anti-PD-1 immunotherapy. The new agent is designed to enhance the immune response against tumors, like melanoma.

Among the 57 participants receiving dostarlimab, 27 of these also received cobolimab. A major pathologic response was experienced by 55.6% of patients with both dostarlimab and cobolimab and only 33.3% in those who received dostarlimab alone. Within the combination treatment, 37.0% experienced a complete response and 18.5% a nearly complete response.

For patients receiving dostarlimab alone, 66.7% showed no response. In the combination of cobolimab and dostarlimab, 40.8% showed no response. Overall survival has not yet been reached in the trial.

Although the results are promising, future confirmatory clinical trials with a larger population and comparison to the standard of care are needed.

---

Tiragolumab, a new immunotherapy agent, was tested in patients with high-risk Stage III melanoma in combination with the drug atezolizumab, an FDA-approved anti-PD-L1 immunotherapy. The new agent is designed to promote the development of active T cells (cancer killing cells).

Among the 34 participants receiving atezolizumab plus tiragolumab, 13 or 47.7% showed a complete pathologic response and 3 showed a partial response. After 12 months, 28 patients were still participating in the trial, and 73.3% of these patients remained recurrence-free from melanoma. In addition, 86.0% of patients were surviving without distant metastasis.

Although the results are promising, there are several limitations. With only 34 patients, the small sample size requires repeating in a larger population. The study also lacked a direct comparison with the standard of care, which is needed for broader interpretation of results.

---

Vidutolimod, a new immunotherapy agent, was tested in patients with high-risk resectable Stage IIIB, C, or D melanoma in combination with the drug pembrolizumab (Keytruda). The new agent is designed to stimulate the production of interferon alpha, which will signal a problem to the rest of the immune systems cells. The agent is encapsulated in a virus-like particle.

The study had 57 participants receiving either vidutolimod and pembrolizumab (n=28) or pembrolizumab alone (n=29). The major pathological response rate was 79.0% in patients on the combination and 58.0% with pembrolizumab alone. The 1-year event free survival was 89.0% among patients treated with the combination and 75.0% with pembrolizumab alone.

Although the results are promising, similar to the other phase 2 studies, this data will need to be repeated in a larger population before they can be broadly interpreted. However, the clinical activity is encouraging.

---

These results were presented in a series of three separate oral talks at the American Society of Clinical Oncology in Chicago on June 3, 2025. Tina Hieken presented, “NeoACTIVATE arm C: Phase II trial of neoadjuvant atezolizumab and tiragolumab for high-risk operable stage III melanoma.” Meghan Mooradian presented, “Randomized phase II study of neoadjuvant (neoadj) anti-PD-1 dostarlimab (D) vs. D + anti-TIM-3 cobolimab (C) in high-risk resectable melanoma (mel) (NEO-MEL-T): Primary analysis.” Ahmad Tarhini presented, “A phase II randomized study of neoadjuvant pembrolizumab (P) alone or in combination with vidutolimod (V) in high-risk resectable melanoma: ECOG-ACRIN EA6194.”