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 31, 2025.
2025 Scientific Highlights
Adjuvant cemiplmab prevents recurrence of cutaneous squamous cell carcinoma in patients at high risk of disease recurrence
6001. Phase 3 trial of adjuvant cemiplimab (cemi) versus placebo (pbo) for high-risk cutaneous squamous cell carcinoma (CSCC).
Danny Rischin (Peter MacCallum Cancer Centre, Melbourne, VIC, Australia) presented the primary analysis of the phase 3 C-POST study comparing the efficacy and safety of adjuvant anti-PD-1 immune checkpoint inhibitor cemiplimab to placebo in patients with cutaneous squamous cell carcinoma (CSCC) at high risk of recurrence after surgery and adjuvant radiotherapy. A subset of patients with CSCC are at high risk of recurrence after surgery and adjuvant radiotherapy, and there are currently no effective systemic therapies to prevent recurrence. All patients enrolled in the study had completed post-operative radiotherapy and met the criteria of one or more high-risk categories. 209 patients were treated with adjuvant cemiplimab, and 206 patients received the placebo. With regards to the primary endpoint of disease-free survival (DFS), cemiplimab was superior to placebo. Median DFS not reached in the cemiplimab arm and 49.4 months in the placebo arm (HR 0.32, p<0.0001), and 24-month DFS rates were 87% for the cemiplimab arm and 64% for the placebo arm. DFS benefit with cemplimab was observed in all prespecified patient subgroups, and efficacy and safety were similar between the two dosing regimens of 350 mg cemplimab every three weeks for 12 weeks vs. 700 mg cemiplimab every 6 weeks for 36 weeks. Cemiplimab was associated with increased freedom from local-regional recurrence (HR 0.2) and with increased freedom from distant recurrence (HR 0.35). Survival data are immature, but recent updates also indicate that cemiplimab also increases survival compared to placebo (HR 0.78). Treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred in 24% of patients in the cemiplimab arm compared to14% in the placebo arm, and two patients in each arm died due to TEAEs. Cemiplimab is the first and only systemic therapy to produce a statistically significant and clinically relevant reduction in disease recurrence in the adjuvant setting in patients at high risk of CSCC recurrence. Results from this study support adjuvant cemiplimab as a new standard of care for patients at high risk of CSCC recurrence.
Exploratory subgroup analyses of the CREST study: Subcutaneous sasanlimab with bacillus Calmette-Guérin (BCG) in BCG-naive, high-risk non–muscle-invasive bladder cancer
4517. Sasanlimab in combination with bacillus Calmette-Guérin (BCG) in BCG-naive, high-risk non–muscle-invasive bladder cancer (NMIBC): Event-free survival (EFS) subgroup analyses based on disease stage from the CREST study.
Thomas Powles (Barts Cancer Centre, Cancer Research UK Experimental Cancer Medicine Centre, Queen Mary University of London, UK) presented exploratory analyses of key subgroups from the CREST study, which investigated anti-PD-1 immune checkpoint inhibitor sasanlimab administered subcutaneously in combination with bacillus Calmette-Guérin (BCG) as induction (IND) and maintenance (MNT) therapy in patients with BCG-naïve, high risk non-muscle invasive bladder cancer. Results from CREST study previously indicated that sasanlimab and BCG significantly improved event-free survival (EFS) compared to BCG alone in patients with BCG-naïve, high-risk NIMBC. Patient subgroups were determined by disease stage at the time of randomization and by PD-L1 status. Patients in Arm A received sasanlimab in combination with BCG as IND and MNT therapy (sasanlimab + BCG-I+M); patients in Arm B received sasanlimab + BCG as IND therapy only (sasanlimab + BCG-I); and patients in Arm C received BCG as IND and MNT therapy (BCG-I+M). Sasanlimab + BCG-I+M prolonged EFS compared to BCG-I+M across the entire patient population (HR 0.68), and potential enrichment was observed in patients with carcinoma in situ (CIS) with or without papillary tumors at baseline (HR 0.53), and recurrence of CIS disease was less frequent in the sasanlimab + BCG-I+M arm compared to the BCG I+M arm. In patients with T1 tumors, 36-month EFS rates were 81.3% in the sasanlimab + BCG-I+M arm and 72.2% in the BCG-I+M arm (HR 0.63). In patients with high-grade Ta or T1 tumors, disease recurrence or progression was less frequent in the sasanlimab + BCG-I+M arm than the BCG-I+M arm. Although patients with CIS had lower baseline PD-L1 expression than patients with T1 tumors (17.8% vs 26.9%), baseline PD-L1 expression was not associated with EFS benefit. Sasanlimab + BCG as induction therapy without maintenance therapy did not favor EFS. 36-month EFS rates of the Sasanlimab + BCG-I group and the BCG-I+M group were 71.5% and 74.8% respectively (HR 1.16), indicating BCG as MNT therapy has an important role in the combination therapy regimen. No new safety signals were identified, and the observed safety profile was consistent with the known profiles of each individual agent. These data further support that subcutaneous sasanlimab + BCG as induction and maintenance therapy has practice-changing potential for the treatment of patients with NMIBC with high risk of recurrence, especially those with CIS and T1 tumors at baseline. More studies are needed to validate predictive biomarkers and to identify the biological mechanisms driving response to sasanlimab + BCG.
Neoadjuvant sacituzumab govitecan combined with pembrolizumab as a bladder-preserving approach for patients with muscle-invasive bladder cancer
4518. First results of SURE-02: A phase 2 study of neoadjuvant sacituzumab govitecan (SG) plus pembrolizumab (Pembro), followed by response-adapted bladder sparing and adjuvant pembro, in patients with muscle-invasive bladder cancer (MIBC).
Andrea Necchi (IRCCS San Raffaele Hospital, Vita-Salute San Raffaele University, Milan, Italy) reported results from SURE-02, phase 2 study of neoadjuvant sacituzumab govitecan (SG) plus pembrolizumab (pembro) followed by response-adapted bladder-sparing adjuvant pembro in patients with muscle-invasive bladder cancer (MIBC). SG is a TROP2-directed antibody drug conjugate, which has previously been shown to exhibit clinical effects against MIBC in the neoadjuvant setting. The standard of care for MIBC is neoadjuvant chemotherapy (CT) followed by radical cystectomy (RC), but approximately 50% of patients are ineligible for or refuse CT, lowering chances of survival. Furthermore, the SURE-01 trial and others investigating neoadjuvant therapies for MIBC raised questions surrounding the necessity for RC in patients who exhibited a complete response to neoadjuvant treatment. The SURE-02 trial was designed to save the bladder based on patient response to neoadjuvant SG + pembro. Patients with MIBC who were ineligible for or refused RC and/or CT received neoadjuvant SG + pembro prior to surgery. For patients who achieved a complete clinical response (cCR) after neoadjuvant SG + pembro, bladder-sparing restage transurethral resection of bladder tumor (reTURBT) was performed in place of RC. Patients received adjuvant/maintenance pembro after reTURBT or RC. 49 patients were treated and evaluated for safety, and 36 patients were evaluated for efficacy: 32 patients received surgery, and 4 patients experienced disease progression. Treatment was well-tolerated; 98% of patients experienced a treatment-related adverse event (TRAE), but most (86%) were grade 1. 3 patients (6%) were unable to complete 4 cycles of neoadjuvant SG + pembro due to TRAEs. In the efficacy-evaluable population, 16 patients (44.4%) achieved a clinical complete response (cCR), 23 patients received bladder-sparing reTURBT, and 2 patients experienced an intravesical relapse after cCR. At a median follow-up of 10 months, the 12-month event-free survival (EFS) rate was 71.3%, and the 12-month metastasis-free survival rate was 84.2%. 100% of the 16 patients who achieved a cCR remained event free with their bladders intact after 12 months, and the 12-month bladder-intact EFS rate for the 23 patients who received reTURBT was 74%. Patients who achieved a cCR had an enriched mutation landscape compared to those with a non-cCR, with median tumor mutation burdens (TMB) of 12 mutations/Mb and 6.6 mutations/Mb, respectively. cCR rates were higher among patients with luminal subtypes subgroups, and increased EFS was associated with higher TROP2 expression and higher mismatch repair signatures. Although more studies are needed to verify the putative tumor biomarkers associated with clinical response, the compelling cCR rate and manageable safety profile suggest SG + pembro may be a safe and effective bladder-preserving approach for patients who refuse or are ineligible for standard of care treatment for MIBC.
Efficacy and safety of BNT142, an mRNA-encoded bispecific T cell engager targeting Claudin 6 in patients with heavily pre-treated solid tumors
2501. First-in-human phase I/II trial evaluating BNT142, a first-in-class mRNA encoded, bispecific antibody targeting Claudin 6 (CLDN6) and CD3, in patients (pts) with CLDN6-positive advanced solid tumors.
Timothy Yap (The University of Texas MD Anderson Cancer Center, Houston, TX, USA) presented the first dose escalation report of BNT142-01, a phase 1/2, open-label, multi-center trial to evaluate BNT142 in patients with CLDN6-positive advanced solid tumors. CLDN6 is an oncofetal protein that is aberrantly activated in testicular, ovarian, non-small cell lung (NSCLC) and other cancers. BNT142 is a novel lipid nanoparticle (LNP)-encapsulated mRNA encoding the anti-CLDN6/CD3 bispecific antibody RiboMab02.1. Particles are taken up in the liver and translated to RiboMab02.1. RiboMab engages both CLDN6-positive tumor cells and T cells to induce killing of tumor cells. 65 patients with CLDN6-positive metastatic or unresectable solid tumors participated in the phase 1 dose escalation study, with 7 weekly doses ranging from 50 ng BNT142/kg to 100 micrograms BNT142/kg. All patients had received all available standard therapies, 66% of patients had received 4 or more prior lines of treatment, and 88% had received 3 or more. Ovarian cancer (n=44), germ cell tumors (n=12), NSCLC (n=5), endometrial cancer (n=1), cholangiocarcinoma (n=2), and epithelioid sarcoma (n=1) were represented in the patient population. Most patients had widespread CLDN6 expression. 63% of patients experienced mild to moderate treatment-related adverse events (TRAEs), 23% of patients experienced TRAEs or treatment related serious adverse events of grade 3 or higher. The majority of TRAEs were grade 1/2 events. Cytokine release was induced in a dose-dependent manner, and increased cytokine levels were most prominent during the first dosing cycles. Levels of translated RiboMab02.1 increased in a dose-dependent manner, especially during the first cycle of treatment. The overall response rate was 11.5%. 7 patients achieved a partial response (PR), and all 7 PRs occurred in patients with ovarian cancer. No correlation was observed between CLDN6 expression levels and best response. Among the 44 patients with ovarian cancer the ORR was 16.7%, and the disease control rate was 76.2%. These results provide the first clinical proof-of-concept for an mRNA-encoded bispecific T cell engager produced in vivo. BNT142 was associated with a manageable safety profile and produced encouraging anti-tumor activity, especially in patients with heavily pretreated ovarian cancer. Enrollment for the BNT142-01 study has concluded, and clinical data from additional patients will be presented at a future date.
Window of opportunity study of lucicebtide, a C/EBP beta antagonist, for recurrent and newly diagnosed glioblastoma
2016. Use of lucicebtide (ST101) in glioblastoma patients by antagonism of C/EBP beta-dependent mesenchymal cell transition and immunosuppressive M2 macrophage polarization.
Fabio Massaiti Iwamoto (Columbia University Irving Medical Center, New York, NY, USA) presented data from a window of opportunity study of lucicebtide in patients with glioblastoma (GBM). Lucicebtide is an antagonist of C/EBP beta, a driver of the mesenchymal transcriptional signature of glioblastoma (GBM), which contributes to its heterogeneous and immunologically “cold.” Phenotype. C/EBP beta is also a transcription factor for immunosuppressive myeloid cells such as immunosuppressive M2 macrophages. The study consisted of two cohorts. 9 patients with recurrent glioblastoma (rGBM) received 2-4 doses of lucicebtide prior to surgery and resumed lucicebtide after surgery to progression, and 9 patients with newly diagnosed GBM (ndGBM) received 2-3 doses of lucicebtide prior to surgery and resumed lucicebtide + chemoradiation after surgery until progression. Lucicebtide was well tolerated, and most adverse events were grade 1 or 2. Progression free survival (PFS) and overall survival (OS) data for patients with ndGBM are still maturing, as 6 of the 9 patients remain alive. All 6 surviving patients have exceeded historic median PFS (4.0 to 6.9 months), and 4 have exceeded historic median OS (14.6 to 17 months). In patients with rGBM, 6 of 9 exceeded historic median PFS (2 months), and 7 of 9 have exceeded historic median OS (5.6 – 9.8 months). 13 of 14 evaluable patients exhibited tumor uptake of lucicebtide, and 8 of 11 exhibited reduced C/EBP beta expression in tumors, indicating target engagement. Patients with stable disease exhibited an increase in tumor-infiltrating CD8 T cells and increased ratio of immunostimulatory M1/immunosuppressive M2 macrophages in the tumor. Spatial transcriptomic analyses indicate lucicebtide can cause significant changes in mesenchymal markers and reduced expression of mesenchymal genes. Lucicebtide has a favorable safety profile, and it can be taken up into GBM tumors changing the GBM tumor microenvironment to be more immunologically “hot,” representing a promising new approach for treating GBM.
Safety and clinical activity of IMA203, a TCR-T cell targeting PRAME, in patients with heavily pretreated melanoma
2508. Phase 1 clinical update of IMA203, an autologous TCR-T targeting PRAME in patients with PD1 refractory metastatic melanoma.
Martin Wermke (University Hospital Carl Gustav Carus, Dresden, Germany) reported results from an ongoing Phase 1a/1b trial of IMA203, an autologous TCR-T targeting PRAME, for recurrent or refractory sold tumors. PRAME is an intracellular protein displayed at high density on the surface more than 50 types of solid tumors, including melanoma. PRAME is not expressed in non-malignant tissues, making it an ideal target for cancer immunotherapies. IMA203, a TCR T cell therapy, recognizes intracellular PRAME-derived peptide on HLA-A*02-01, which has a prevalence of 45% in the Western population. Patients received lymphodepletion before IMA203 infusion, followed by low-dose IL-2. 74 HLA-A*02-01-positive, PRAME-positive patients were included in safety population. 1 patient received lymphodepletion but not IMA 203, 27 patients participated in the phase 1a dose escalation stage of the study, and 46 patients in the Phase 1b Dose Expansion stage received the recommended phase 2 dose (RP2D) of 1-10 x 109 TCR T cells. The melanoma efficacy population (melanoma subgroup) consisted of 33 patients who received the RP2D of IMA203; 14 patients had cutaneous melanoma, and 16 had uveal melanoma. Patients in the total safety population had received a median of 3 prior lines of systemic treatment, and the melanoma population had received a median of 2 prior lines. IMA203 was well-tolerated, and the most frequent treatment-emergent adverse events were associated with lymphodepletion. 95% of patients experienced cytokine release syndrome, but most cases were grade 1 or 2. Tolerability in the melanoma subgroup was consistent with the overall patient population. The confirmed overall response rate (cORR) in the melanoma subgroup was 56%, and responders included patients with cutaneous (cORR 50%) and uveal (cORR 67%) disease. At a median follow-up of 13.4 months, the median duration of response in the melanoma subgroup was 12.1 months, and at a median follow-up of 14.4 months, the median progression free survival and median overall survival were 6.1 months and 15.9 months, respectively. Patients in the melanoma subgroup also exhibited tumor shrinkage at metastases throughout the body. Given its favorable safety profile and durable objective responses against cutaneous melanoma and uveal melanoma, IMA203 represents a promising therapeutic option for patients with heavily pretreated melanoma. A phase 3 trial of IMA203 for previously treated or metastatic cutaneous melanoma (SUPRAME) is underway.