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 May 30, 2025.
2025 Scientific Highlights
Continued clinical benefits of nivolumab and ipilimumab for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer
3501. Nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) or NIVO monotherapy for microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC): Expanded analyses from CheckMate 8HW.
Heniz-Josef Lenz (University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA) presented expanded analyses and longer follow-up results from the phase 3 CheckMate 8HW study comparing nivolumab with ipilimumab (nivo + ipi) to chemotherapy (chemo) or nivolumab (nivo) for patients with microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Previous reports of CheckMate 8HW demonstrated that nivo + ipi is associated with superior progression free survival (PFS) compared to chemo in the first-line (1L) setting and superior PFS compared to nivo across all lines of therapy, leading to the approval of nivo +ipi for 1L treatment for patients with MSI-H/dMMR mCRC in the United States, European Union, and other countries. 839 patients were randomized 2:2:1 to receive nivo + ipi (n=353), nivo (n=354), or chemo (n=132). 57% of patients in the nivo + ipi arm, 57% of patients the nivo arm and 77% of patients in the chemo arm had not received prior therapy. At the 47-month follow-up, nivo + ipi continued to exhibit clinically meaningful benefits in PFS compared to chemo in the 1L setting in patients with MSI-H/dMMR mCRC. Median PFS in the nivo + ipi arm (n=171) was 54.1 months, compared to 5.9 months for the chemo arm (n=84; HR 0.21), and 3-year PFS rates were 69% and 11%, respectively. PFS2 was defined as the time from randomization to progression after subsequent systemic therapy, start of second subsequent systemic therapy, or death. PFS2 was also improved in the nivo + ipi arm in the 1L setting: median PFS2 was not reached in the nivo + ipi arm and 30.3 months in the chemo arm. Nivo + ipi was associated with a 72% reduction of death or progression after first subsequent therapy compared to chemo, despite 71% of patients in the chemo arm receiving subsequent immunotherapy. When compared to nivo for all lines of therapy, nivo + ipi was also consistently associated with PFS benefits, with median PFS of 54.1 months in the nivo + ipi arm and 18.4 months in the nivo arm (HR 0.64). 36-month PFS2 rates were 80% in the nivo + ipi arm, compared to 66% in the nivo arm. Overall response rate (ORR) in the nivo + ipi arm was significantly higher than the nivo arm (71% vs. 58%, respectively, p=0.0011). Treatment-related adverse events (TRAEs) for both groups were well managed and consistent with each treatment component. In an exploratory analysis of patients in the nivo+ ipi arm with grade 3/4 TRAEs, 3-year PFS rates (74%) and ORR 77% were consistent with the overall study population. Nivo + ipi exhibited superior PFS and improved PFS2 across all lines of treatment, providing further support for nivo + ipi as the standard of care for patients with MSI-H/dMMR mCRC.
Clinical efficacy and safety of triplet treatment with anti-PD-L1 adebrelimab, bevacizumab, and cisplatin/carboplatin for metastatic triple negative breast cancer in the brain
1018. A phase II clinical study of adebrelimab and bevacizumab combined with cisplatin/carboplatin in triple-negative breast cancer patients with brain metastases.
Tin Li (Fudan University Shanghai Cancer Center) presented data from the ABC study, a single-arm, phase 2 clinical trial of anti-PD-L1 monoclonal antibody adebralimab combined with anti-VEGF monoclonal antibody bevacizumab and cisplatin/carboplatin for patients with triple-negative breast cancer (TNBC) with active brain metastases. Brain metastases of TNBC are lethal and lack therapeutic options. Prior studies suggest that PD-(L)1 inhibitors, bevacizumab, and cisplatin/carboplatin may be an effective treatment. 35 patients with TNBC and brain metastases participated in the study. 43% of patients were experiencing neurological symptoms, and 80% of patients had not received prior treatment for brain metastases. The objective response rate in the central nervous system (CNS-ORR) was 77%, with 5 patients achieving a complete response. The clinical benefit rate in the CNS (CNS-CBR) was 80%. At a median follow-up of 17.5 months, the median progression free survival in the CNS (CNS-PFS) was 11.5 months, median PFS was 8.3 months, and overall survival data were immature at the time of data cutoff. Subgroup analyses suggested that ORR was higher among patients with fewer (1-3) CNS lesions and CNS-PFS and PFS were improved among patients with PD-L1-expressing tumors (CPS >= 1) and among patients with immunomodulatory type disease, as defined by Fudan TNBC classification. All patients experienced treatment-related adverse events, and 57% of patients experienced TRAEs of grade 3 or 4. TRAEs were manageable, and no treatment-related deaths were reported. The triplet treatment of adebrelimab, bevacizumab, and carboplatin/cisplatin is first regimen to demonstrate high intracranial anti-tumor activity and clinical benefits. More studies are needed to compare the benefits associated with this triple treatment to other therapies and to validate PD-L1 status and Fudan TNBC classification as predictors of therapeutic efficacy.
Clinical efficacy of a telomerase-targeting therapeutic vaccine for newly diagnosed glioblastoma
2006. A phase II study of an anti-telomerase CD4+ T-helper vaccine (UCPVax) with or without temozolomide in newly diagnosed glioblastoma.
Antoine Carpentier (Hopital Saint-Louis, Paris, France) presented a multicenter phase 2a study of UCPVax, a CD4+ helper T cell-targeting peptide vaccine composed of helper peptides UCP3 and UCP4 from the telomerase (TERT) protein. TERT is highly expressed in 80-90% of cases of primary glioblastoma (GBM), making it a rational target for immunotherapy. Radiotherapy combined with chemotherapy temozolomide (TMZ) followed by TMZ alone is the standard of care for GBM. Patients were vaccinated with UCPVax during the adjuvant phase of TMZ treatment. Because TMZ is a lymphodepleting agent, the study also addressed whether TMZ impaired or enhanced the immunogenic efficacy of UCPVax. Patients with non-mutated IDH1 GBM enrolled in the study one month after completing concurrent radiotherapy and TMZ. Patients in Cohort A (n=31) received UCPVax alone, and Cohort B (n=30) received UCPVax and six monthly cycles of TMZ. All patients in Cohort A and 50% of patients in Cohort B had unmethylated MGMT promoters, which is associated with poor prognosis. TERT-specific CD4+ T cells were detectable ex vivo in 83% of patients in Cohort A and 69% of patients in Cohort B, suggesting concurrent TMZ does not significantly compromise vaccine-induced immunity. Among patients with unmethylated MGMT (n=46), progression free survival (PFS) was 8.5 months, compared to 12.6 months in patients with methylated MGMT (n=15). Umethylated MGMT was also associated with lower overall survival (OS) compared to methylated MGMT (18 months vs. 27.9 months). Median OS for cohort A (unmethylated MGMT, no TMZ) was 17.9 months, and median OS for patients in cohort B (treated with TMZ) with unmethylated MGMT was 20.2 months. 28/46 patients with unmethylated MGMT achieved a radiological response, and 12/15 patients with methylated MGMT achieved a radiological response. Tumor infiltrating lymphocytes against TERT were detected in 3 vaccinated patients who underwent surgery at recurrence and not detected in unvaccinated patients. Epitope spreading against additional tumor associated antigens was observed in 15 of 26 evaluable patients in Cohort A and 14 of 29 evaluable patients in Cohort B, and in patients with unmethylated MGMT, overall survival was improved in patients who exhibited epitope spreading compared to those who did not (p=0.034). Multivariate analyses indicated that epitope spreading (p=0.0165) and MGMT methylation (p=0.0416) were associated with changes in overall survival. These data indicate that UCPVax is immunogenic in patients with newly diagnosed GBM, concurrent treatment with TMZ does not significantly affect vaccine-induced immunity, and UCPVax may promote survival in patients with GBM, including those with unmethylated MGMT. A phase 2 trial comparing the standard of care with UCPVax and anti-PD-1 therapy combined with the standard of care is scheduled to begin in September 2025.