The Society for Immunotherapy of Cancer (SITC) is pleased to present highlights of the latest advances in cancer immunotherapy emerging from the 2025 ASCO Annual Meeting on June 3, 2025.
2025 Scientific Highlights
Subgroup analyses of COMPASSION-16: Bispecific PD-1 x CTLA-4 antibody cadonilimab plus chemotherapy with or without bevacizumab for first-line persistent, recurrent, or metastatic cervical cancer
5509. Cadonilimab plus platinum-based chemotherapy ± bevacizumab for persistent, recurrent, or metastatic cervical cancer: Subgroup analyses of COMPASSION-16.
Xiaohua Wu (Fudan University Shanghai Cancer Center, Shanghai, China) presented planned subgroup analyses of the COMPASSION-16 study, a phase 3 multicenter trial investigating the efficacy of cadonilimab, a PD-1 x CTLA-4 bispecific monoclonal antibody, in combination with chemotherapy as first-line treatment for patients with persistent, metastatic, or recurrent cervical cancer. Previous interim reports of COMPASSION-16 indicate cadonilimab combined with chemotherapy with or without bevacizumab significantly improves progression-free survival (PFS) and overall survival (OS) compared to chemotherapy with or without bevacizumab. Patients in the cadonilimab group (n=222) received cadonilimab + paclitaxel and cisplatin or carboplatin +/- bevacizumab, followed by maintenance therapy with cadonilimab +/- bevacizumab. Patients in the placebo group (n=223) received placebo + paclitaxel and cisplatin or carboplatin +/- bevacizumab, followed by maintenance therapy with placebo +/- bevacizumab. In the overall patient population, median PFS was 13.3 months for the cadonilimab group and 8.2 months for the placebo group (HR 0.62, p<0.0001), and median OS was not reached and 22.8 months, respectively (HR 0.64, p=0.0011). All pre-specified patient subgroups analyzed showed PFS and OS benefits from cadonilimab, even in groups considered high risk. Of note, among patients who received prior concurrent chemoradiotherapy (CCRT), cadonilimab was associated with greater PFS and OS benefits (HR 0.55 and 0.54, respectively) compared to patients who had not received prior CCRT (PFS HR 0.67 and OS HR 0.76, respectively). Cadonilimab was also associated with greater survival benefits among ~40% of patients who were not eligible for bevacizumab. Median PFS was 11.7 months in the cadonilimab group (n=89), compared to 6.7 months in the placebo group (n=91; HR 0.44), and median OS was 28.2 months in the cadonilimab group, compared to 15.1 months in the placebo group (HR 0.50). Cadonilimab extended PFS and OS among patients 65 years of age or older (HR 0.39 and 0.49, respectively). These results further support cadolinimab as an option for first-line therapy for persistent, recurrent, or metastatic cervical cancer.
Efficacy and safety data of IBI363, a PD-1/IL-2 bispecific antibody, for advanced non-small cell lung cancer
8509. First-in-class PD-1/IL-2 bispecific antibody IBI363 in patients (Pts) with advanced immunotherapy-treated non-small cell lung cancer (NSCLC).
Jianya Zhou (The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China) reported results from a phase I, multicenter, first-in-human study of IBI363 in patients with advanced NSCLC. IBI363 is a novel, first-in-class PD-1/IL-2alpha-bias bispecific antibody fusion protein that blocks PD-1 checkpoint and activates exhausted T cells by cis-activating alpha-bias IL-2, potentially meeting an unmet need for patients with immunologically “cold” and/or immune checkpoint inhibitor-resistant tumors. 136 patients with advanced NSCLC that had been previously treated with immunotherapy were enrolled in the study. 67 patients had EGFR wild type squamous cell carcinoma (sqNSCLC), and 58 patients had EGFR wild type adenocarcinoma (adenoNSCLC). Within the sqNSCLC cohort, 28 patients were treated at low doses of IBI363 (1 mg/kg every two weeks or 1.5 mg/kg every three weeks), and 31 patients were treated with higher dose IBI363 (3 mg/kg every three weeks). For patients with sqNSCLC treated with low dose IBI363, the confirmed objective response rate (cORR) was 25.9%, compared to a cORR 36.7% for patients who received the higher dose. One patient with sqNSCLC who received the higher dose of BIB363 achieved a complete response. The median duration of response (mDoR) was 10.2 months with low dose IBI363 and not reached with higher dose IBI363, and the disease control rate (DCR) was 66.7% with low dose IBI363 and 90.0% with higher dose IBI363. Median progression-free survival (mPFS) was 5.5 months for patients receiving low dose IBI363 and 9.3 months for patients receiving higher dose IBI363, and median overall survival (mOS) was 15.3 months and not reached, respectively. Within the adenoNSCLC cohort, 30 patients were treated at low doses of IBI363 (0.6 mg/kg or 1 mg/kg every two weeks or 1.5 mg/kg every three weeks), and 25 patients were treated with a higher dose of IBI363 (3 mg/kg every three weeks). For patients with adenoNSCLC treated with low dose IBI363, the cORR was 13.8%, compared to 24.0% for patients treated with the higher dose. mDoR was not reached for both dosing groups, and the DCR was 62.1% for patients treated with low dose IBI363 and 76.0% for patients treated with the higher dose. mPFS was 2.7 months for patients receiving low dose IBI363 and 5.6 months for patients receiving higher dose IBI363, and mOS was 17.5 months and not reached, respectively. Responses were observed in all patient subgroups regardless of PD-L1 status. Treatment related adverse events (TRAEs) of grade 3 or 4 were observed in 17.7% of patients receiving low dose IBI363, compared to 43.9% of patients receiving higher dose IBI363, and most of these TRAEs were arthralgia and rash. TRAEs lead to treatment discontinuation in 4 patients receiving low dose IBI363 and 4 patients receiving higher dose IBI363. With its encouraging clinical responses and manageable safety profile, IBI363 represents a promising new option for patients with advanced NSCLC that did not respond to prior immunotherapy.
Efficacy and safety of BNT327, a PD-L1 x VEGF-A bispecific antibody for first-line treatment of unresectable malignant mesothelioma
8511. First report of efficacy and safety results from a phase 2 trial evaluating BNT327/PM8002 plus chemotherapy (chemo) as first-line treatment (1L) in unresectable malignant mesothelioma.
On behalf of Ying Cheng (Jilin Cancer Hospital, Changchun, China), Liang Zhang (Jilin Cancer Hospital, Changchun, China) reported the first results of a single arm phase 2 trial of BNT327, a PD-L1 x VEGF-A bispecific antibody, for first-line treatment of patients with unresectable malignant mesothelioma. In addition to binding to PD-L1 on tumors to promote T cell-mediated anti-tumor activity, BNT327 also binds to VEGF, blocking immunosuppressive VEGF signaling in the tumor microenvironment and normalizing tumor vasculature. BNT327 has exhibited encouraging preliminary activity and a manageable safety profile for small cell lung cancer and non-small cell lung cancer. 31 patients with unresectable malignant mesothelioma with no prior systemic therapy were treated with BNT327 and chemotherapy, followed by maintenance therapy with BNT327 until progression or disease toxicity. 23 patients in the study had malignant plural mesothelioma (MPM), and 8 patients had malignant peritoneal mesothelioma (MPeM). The confirmed objective response rate (cORR) was 51.6% in the total patient population, and cORR was 43.5% among patients with MPM and 75.0% among patients MPeM. Disease control rates were 90.3% for all patients, 87.0% for patients with MPM and 100% for patients with MPeM. At a median follow-up of 22.3 months, median progression-free survival was 16.6 months for all patients, 15.8 months for patients with MPM, and not yet mature for patients with MPeM. Survival data are not mature, but the 15-month overall survival rates for all patients, patients with MPM, and patients with MPeM were 77.4%, 82.6%, and 62.5%, respectively. All patients in the study experienced treatment-related adverse events (TRAEs), and 93% of patients experienced a TRAE of grade 3 or 4. No treatment-related deaths occurred, 19.4% of patients experienced TRAEs leading to dose reduction, and 19.4% of patients experienced TRAEs leading to dose discontinuation. Although a larger, broader group of patients with malignant mesothelioma is needed to validate these results BNT327 showed promising efficacy as first-line treatment for malignant mesothelioma. Furthermore, this study is one of the first to report results of immunotherapy-based treatment for peritoneal mesothelioma, thus addressing a highly unmet medical need.
Neoadjuvant vidutolimod, a TLR9 agonist, in combination with perioperative pembrolizumab for stage III, high-risk resectable melanoma
LBA9505. A phase II randomized study of neoadjuvant pembrolizumab alone or in combination with vidutolimod in high-risk resectable melanoma: ECOG-ACRIN EA6194.
Ahmad A. Tarhini (H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA) reported results from a phase 2 study investigating the addition of neoadjuvant vidutolimod to perioperative pembrolizumab for high-risk resectable melanoma. Vidutolimod is a TLR9 agonist packaged within a virus-like particle and is administered intratumorally. Vidutolimod induces a Type I interferon response, stimulating innate and adaptive anti-tumor immune responses, and it has exhibited promising clinical activity against advanced melanoma. 57 patients with stage IIIB-D resectable melanoma enrolled in the study. Patients in Arm A (n=29) received neoadjuvant pembrolizumab then adjuvant pembrolizumab after surgery, and patients in Arm B (n=28) received neoadjuvant pembrolizumab with intratumoral vidutolimod then adjuvant pembrolizumab after surgery. Due to disease progression, 4 patients in Arm A and 1 patient in Arm B did not receive surgery. Analyses included the entire patient population (n=57), including those who did not receive surgery. The pathologic complete response rate was 48% in Arm A and 71% in Arm B, and 59% of patients in Arm A and 79% of patients in Arm B achieved a major pathologic response. At a median follow-up of 19 months, median event-free survival was 75% in Arm A and 89% in Arm B. Of the 56 patients with evaluable radiological response data, 50% of patients in Arm A and 43% of patients in Arm B achieved a preoperative radiologic response. Grade 3 or 4 adverse events were observed in 25% of patients in Arm A and 29% of patients in Arm B, and no grade 5 events were observed. With its manageable safety profile and encouraging pathologic response rate, neoadjuvant vidutolimod in combination with perioperative pembrolizumab represents a promising new option for treating patients with high-risk resectable melanoma. Comprehensive biomarker analyses are ongoing, and the reported efficacy and safety results support larger phase 3 trial of this treatment regimen.
Analyzing a reduction in the duration of anti-PD-1 therapy for patients with metastatic melanoma
LBA9508. Comparison of 1 year versus minimum 2 years of anti-PD1-based immunotherapy as first-line treatment for metastatic melanoma: Results of the DANTE phase III trial.
Sarah Danson (University of Sheffield, Sheffield, UK) presented results from the phase 3 DANTE trial which evaluated whether patients with advanced melanoma receiving one year of first-line anti-PD-1 therapy would achieve and maintain similar clinical outcomes as patients receiving the same standard of care for two years or more. First line therapy for metastatic melanoma is an anti-PD-1 based regimen regardless tumor BRAF mutation. Anti-PD-1 therapy is licensed for first-line treatment metastatic melanoma until tumor progression, but the optimal duration of immune checkpoint blockade is unclear for melanoma and other tumor types. There is an unmet need to optimize duration of anti-PD-1 therapy to reduce the risk of long-term side effects and to reduce cost. Patients with advanced melanoma who were progression-free after 1 year of treatment with anti-PD-1 therapy +/- anti-CTLA-4 therapy were randomized 1:1 to continue treatment for at least 2 years in the absence of disease progression or unacceptable toxicity (Arm A,) or to stop treatment with the option of restarting in the event of progression (Arm B). Recruitment for the trial was a challenge, partly due to the COVID-19 pandemic and the changing treatment landscape for melanoma. Due to low enrollment, DANTE closed early, with 83 patients randomized to Arm A and 83 to Arm B. At a median follow-up of 29 months, one-year progression-free survival (PFS) rates were 87.6% in Arm A, and 80.2% in Arm B, with an adjusted HR of 3.0, indicating that stopping treatment at one year is not inferior to continuing treatment. 12% of patients in Arm A and 17% of patients in Arm B died, and as expected, 25% of patients in Arm A experienced an adverse event of Grade 3 or higher, compared to 8% of patients in Arm B. There were no significant differences between the two arms regarding patient-reported quality of life. The low enrollment of the DANTE trial underscores the challenge of recruiting patients to randomized trials that investigate de-escalation of treatment. Although results indicate that stopping anti-PD-1 therapy after one year is not inferior to at least two years of treatment, the study was underpowered and closed early. Thus, continuing anti-PD-1 therapy for at least two years continues to be the standard of care for first-line treatment of advanced melanoma. Health economic analyses of DANTE will be reported separately.