We are pleased to present highlights of the latest advances in immunotherapy emerging from the 2026 ASCO Annual Meeting, May 30, 2026.
(Thanks to Chinmay Jani, MD and Terri Holzen, PhD for compiling these scientific highlights)
Tumor-specific MHC-II as a prospective biomarker of response to perioperative chemoimmunotherapy for gastric cancer
2513. Perioperative tislelizumab plus chemotherapy versus chemotherapy in MHC-II positive /MHC-II negative locally advanced GC/GEJC: A prospective randomized, open-label, biomarker-driven, phase 2 trial
Xiangdong Cheng, MD (Zhejiang Cancer Hospital, Hangzhou, Zhejiang Province, China) presented a phase 2 biomarker-stratified trial to evaluate the effectiveness of perioperative chemotherapy combined with tislelizumab compared to chemotherapy alone for patients with locally advanced gastric cancer (GC) that was tumor-specific MHC-II-positive (tsMHC-II). While the MATTERHORN trial established perioperative immunochemotherapy for gastric cancer, PD-L1 was not an effective biomarker to identify patients who were more likely to respond to perioperative therapy. Given the role of MHC-II in antigen presentation and CD4 T cell activation, the goal of this study was to evaluate the efficacy of perioperative immunochemotherapy versus chemotherapy alone in patients with cT3-4aN+M0 GC or gastroesophageal junction cancer (GEJC) stratified by tsMHC-II status. Patients in Arm A were tsMHC-II-positive and received 3 cycles tislelizumab with chemotherapy (SOX/XELOX) prior to surgery, followed by 3 cycles of chemotherapy and tislelizumab and then 11 cycles of tislelizumab after surgery (perioperative chemoimmunotherapy). Patients in Arm B were tsMHC-II-positive and received 3 cycles of chemotherapy before and after surgery (perioperative chemotherapy). Arm C was tsMHC-II-negative and received perioperative chemoimmunotherapy, and patients in Arm D were tsMHC-II-negative and received perioperative chemotherapy. Primary endpoint was major Pathologic response rate (MPR) 34 patients were enrolled in each arm. Baseline characteristics were well balanced across all four treatment arms, with similar distributions in age, sex, ECOG performance status, tumor location, clinical stage, Lauren classification, signet-ring cell composition, chemotherapy backbone, and PD-L1 CPS. In patients who were tsMHC-II-positive, tislelizumab significantly improved the MPR rates, with MPRs occurring in 61.76% in patients in Arm A versus 26.47% in Arm B (p=0.003). Tislelizumab did not significantly affect MPR rates in patients who were tsMHC-II negative, with MPR rates of 23.53% and 26.47% for Arms C and D, respectively. Similar trends were seen with pathologic complete response (pCR) rates, with 32.35% of tsMHC-II-positive patients who received perioperative chemotherapy achieving a pCR, compared to 8.82% of tsMHC-II-positive patients who received perioperative chemotherapy (p=0.016). Among patients who were tsMHC-II-negative, 5.86% of patients who received perioperative chemoimmunotherapy achieved a pCR, compared to 8.82% of patients who received perioperative chemotherapy. When patients were stratified by PD-L1 expression, patients with PD-L1 CPS >= 5, perioperative chemoimmunotherapy trended toward higher pCR and MPR rates compared to perioperative chemotherapy (pCR rates 16.1% versus 3.3% and MPR rates 41.9% versus 23.3%), but these differences were not statistically significant. Tislelizumab had no effect on pCR and MPR rates in patients with PD-L1 CPS < 5. No new safety signals were identified with tislelizumab in combination with perioperative chemotherapy, and the safety profile of the combination therapy was manageable. This is the first prospective investigation of tsMHC-II as a biomarker for guiding perioperative immunotherapy in gastric cancer, and these early data indicate that tsMHC-II has promise in guiding perioperative treatment for GC/GEJC. A phase 3 trial (NCT07068516) comparing perioperative tislelizumab and chemotherapy to perioperative placebo and chemotherapy is in progress.
Incorporating thymosin alpha-1 into radioimmunotherapy regimens for advanced solid tumors
2516. PRaG 5.0: Personalized thymosin alpha-1 and radioimmunotherapy for advanced refractory solid tumors - Data from an expanded cohort
Yuehong Kong (The Second Affiliate Hospital of Soochow University, Suzhou, China) presented a phase 2 study investigating the incorporation of thymosin alpha-1 (Ta-1) into the PRaG regimen of a PD-1 inhibitor combined with radiotherapy and GM-CSF to preserve lymphocytes and enhance anti-tumor immunity in recurrent or metastatic advanced solid tumors. Thymosin alpha-1 (Ta-1) is a peptide hormone produced by the thymus with immune-modulating properties. Radiotherapy-induced lymphopenias can affect the efficacy of immunotherapy, and past studies have indicated that Ta-1 maintains lymphocyte counts and reduces the incidence of severe lymphopenia in patients receiving chemoradiotherapy. Patients received two or more cycles of Ta-1 combined with the PRaG regimen, followed by PD-1 inhibitor combined with Ta-1. In the intent to treat patient population (n=39), the objective response rate was 30.8% (12/39). Four patients achieved a complete response, and 8 patients achieved a partial response. Median progression-free survival was 4.3 months, and median overall survival was not reached. 23 patients (59.0%) experienced treatment-emergent adverse events (TEAEs), and 4 TEAEs were grade 3 or higher. No serious TEAEs, TEAEs leading to permanent discontinuation of treatment, or TEAEs leading to death were observed. Patients who responded to treatment exhibited higher levels of CD8+ effector memory T (T EM) cells at baseline and early in treatment, compared to non-responders, suggesting elevated CD8+ T EM cells may predict clinical efficacy and that Ta-1 may drive expansion of these cells, especially in responders. Single-cell sequencing indicated a higher clonality in CD8+ T cells expressing Granzyme K in responders and in patients with disease control. TRDV2-CD8+ T cell expansion was associated in patients with progressive disease. Although additional studies are needed to validate these results and identify the mechanisms underlying patient responses, incorporating Ta-1 may be a promising approach to improve the efficacy and safety of combination therapy strategies involving radiation and immunotherapy.
REGOMUNE: Avelumb combined with the anti-angiogenic agent regorafenib for HPV-associated cancer
2517. Evaluation of the combination of regorafenib + avelumab in patients with HPV-associated cancer: The phase II REGOMUNE study
Sophie Cousin (Institut Bergonié, Bordeaux, France) presented results from REGOMUNE, a French multi-center open-label phase 2 trial investigating the anti-angiogenic multi-kinase inhibitor regorafenib in combination with avelumab for advanced or metastatic HPV-driven solid tumors. HPV-associated solid tumors exhibit limited response to immune checkpoint inhibitors (ICI), and metastatic HPV-associated malignancies have limited treatment options and poor prognosis, indicating a need for novel strategies to improve the efficacy of ICI for HPV-associated cancers. REGOMUNE builds upon previous studies that suggest that combining anti-angiogenic agent with immunotherapy may reshape tumor immune microenvironment and enhance the efficacy of ICI. 42 patients with advanced or metastatic HPV-induced (p16+) solid tumors with no previous treatment with regorafenib or avelumab were treated with regorafenib and avelumab. Median age of patient population was 62 with 85.7% (36) females. Patients had received a median of two prior lines of therapy, with a range of 0 to 7 prior lines. 81% of patients had not received prior antiangiogenic agents, and primary sites represented in this patient population included anal (40.5%), cervical(30.9%), vaginal (11.9%), and vulvar (4.8%). At a median follow-up of 18.3 months, 88.1% of patients experienced a treatment-related adverse event (TRAE), and the most common TRAEs were fatigue (66.6%), palmar-plantar erythrodysesthesia (50.0%), and oral mucositis (45.2%). 59.5% of patients experienced a TRAE of grade 3 or 4, and there was one TRAE leading to death (cachexia related to regorafenib). 78.6% of patients modified treatment due to TRAEs, and 42.9% of patients discontinued treatment due to adverse events. In the efficacy evaluable population (n=33), the 6-month disease control rate was 45.5% (15/33) with 11 patients experiencing a partial response (PR), and 4 patients experienced stable disease (SD). Best Overall response included 12 PR and 11 SD with DCR of 69.7%. Overall, 21 patients experienced some tumor shrinkage with median duration of response of 3.7 months, median progression-free survival (PFS) of 5.3 months, and median overall survival of 15 months. PFS was better among patients with no prior ICI exposure compared to patients with prior ICI exposure (median PFS 5.9 months and 3.6 months, respectively). REGOMUNE is the first phase 2 study to show clinically meaningful efficacy when combining an anti-angiogenic agent with an ICI. Analyses to identify biomarkers associated with durable responses are ongoing.
To learn about another approach to overcome resistance to immune checkpoint inhibitors in HPV-associated cancers, read this article from Ghosh et al in JITC.
Long-term follow-up of KEYNOTE-522: Neoadjuvant pembrolizumab plus platinum-containing chemotherapy followed by adjuvant pembrolizumab for high-risk early-stage triple negative breast cancer
507. Neoadjuvant pembrolizumab or placebo plus chemotherapy followed by adjuvant pembrolizumab or placebo for high-risk early-stage TNBC: Final analysis results from the phase 3 KEYNOTE-522 study
Javier Cortes (International Breast Cancer Center (IBCC), Pangaea Oncology, Quiron Group, Medica Scientia Innovation Research (MedSIR), Barcelona, Spain) reported the final, long-term follow-up from the KEYNOTE-522 study. KEYNOTE-522 (NCT03036488) showed statistically significant and clinically meaningful improvements in pathologic complete response (pCR), event-free survival (EFS), and overall survival (OS) in patients receiving pembrolizumab (pembro) and platinum-containing chemotherapy (chemo) for high-risk early-stage triple negative breast cancer (TNBC), and this regimen is now included in standard treatment guidelines. Patients with previously untreated, non-metastatic, centrally confirmed TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC) were randomized 2:1 to receive neoadjuvant pembro (n=784) or placebo (n=390) plus chemotherapy followed by adjuvant pembro or placebo. Dual primary endpoints were pCR (ypT0/Tis ypN0) and EFS with OS as key secondary endpoint. At a median follow-up of 93.8 months, neoadjuvant pembro and chemo followed by adjuvant pembro (pembro + chemo/pembro) was associated with improved EFS (78.3%) compared to neoadjuvant placebo and chemo followed by adjuvant placebo (69.8%; HR 0.68; 0.54-0.86), and EFS of all patient subgroups analyzed benefited from pembro + chemo/pembro. EFS was improved in patients who achieved a pathologic complete response (pCR) with pembro + chemo/pembro, compared to those with a pCR with placebo + chemo/placebo (HR 0.68) and in patients who did not achieve a pCR (HR 0.78). Similar trends were observed regarding OS. Median OS with pembro + chemo/pembro was 85.1%, compared to 77.2% with placebo + chemo/placebo (HR 0.64; 0.49-0.85). OS of all patient subgroups favored pembro + chemo/pembro, and pembro + chemo/pembro was associated with improved OS compared to placebo + chemo/placebo in patients who achieved a pCR (HR 0.64, 0.37-1.14) and in patients who did not achieve a pCR (HR 0.76, 0.55-1.03). Pembro + chemo/pembro also improved progression-free or distant recurrence-free survival compared to placebo + chemo/placebo (82.9% vs. 74.2%, respectively, HR 0.64). Of note, the benefit of pembro on EFS and OS was generally consistent across most prespecified subgroups, including those defined by PD-L1 expression, nodal status, and disease stage. At the 93.8 months follow-up, no new safety signals were observed, and safety profiles were consistent with prior analyses and with known profiles of pembro and chemo. At a median follow-up of almost 8 years, pembro + chemo/pembro continues to provide substantial, durable, and clinically meaningful survival benefits with a manageable safety profile, confirming prior interim analyses of KEYNOTE-522. This final analysis further supports neoadjuvant pembrolizumab plus platinum-containing chemotherapy, followed by adjuvant pembrolizumab as a standard of care for patients with high-risk, early-stage TNBC.
Clinical outcomes in patients receiving afami-cel, a TCR-engineered T cell therapy for advanced synovial sarcoma
11505. Pooled analysis of clinical outcomes with afamitresgene autoleucel (afami-cel) in metastatic synovial sarcoma
Sandra P. Angelo (Memorial Sloan Kettering Cancer Center, New York, NY, USA) reported pooled results of phase 1 and phase 2 trials of afamitresgene autoleucel (afami-cel) in patients with advanced synovial sarcoma. Afami-cel is a TCR-engineered T cell therapy targeting melanoma-associated antigen A4 (MAGEA4) in patients with eligible HLA-A*02 types, and it is the first TCR-engineered T cell therapy approved by the United States Food and Drug Association. This analysis analyzed the synovial sarcoma pilot trial and the SPEARHEAD trial, representing 153 patients, the largest dataset of patients who received afami-cel for advanced synovial sarcoma. HLA-A*02 positive patients underwent leukapheresis, followed by lymphodepleting chemotherapy containing fludarabine and cyclophosphamide and then infusion with afami-cel. The median age of the patients was 40 years old, and 54.2% of the patients were male. Patients had received a median of 2 prior systemic therapies prior to leukapheresis. 41.8% of patients received bridging therapy between leukapheresis and lymphodepletion. The objective response rate was 43.8%. The median time to response was 5.4 weeks, and 7 patients experienced a complete response. Responses were durable, with a median duration of response of 7.1 months. Median progression-free survival (PFS) was 4.0 months, and median PFS was significantly prolonged in responders compared to non-responders (9.1 months vs. 2.1 months, p<0.0001). Median overall survival (OS) was 20.2 months, and median OS was 37.5 months among responders, compared to 10.9 months among non-responders (p<0.0001).For Best overall response, 7 patients (4.6%) had complete response, 60 (39.2%) had PR and 70 (45.8%) had SD. Overall response rates were enriched in patients with H scores of 200 or more and in patients with lower tumor burden (sum of lesion diameter (SLD) < 100 mm). Cytopenias were the most common adverse events of grade 3 or higher, and prolonged cytopenias occurred in 8% to 14% of patients. Cytokine release syndrome (CRS) occurred in 73.2% of patients, and most cases were grade 1 or 2 with 3.3% of patients experiencing CRS of grade 3 or 4. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 6 patients (4.4%), and cases were grade 1 (n=5) or grade 2 (n=1). Two fatal adverse events occurred: one fatality from aplastic anemia, and one fatality from septic shock. Afami-cel is associated with clinically meaningful durable responses, encouraging survival outcomes, and a manageable safety profile, providing a much-needed treatment option for patients with synovial sarcoma. Given that synovial sarcoma is a rare disease and the need to select patients with an HLA biomarker, randomized clinical trials are not feasible, but there is an unmet need to identify correlates of response and resistance to afami-cel for synovial sarcoma.
Three-year survival analysis from the IGNYTE trial: RP1 plus nivolumab for anti-PD-1 failed melanoma
9518. A 3-year landmark overall survival analysis of RP1 plus nivolumab in patients with anti-PD-1-failed melanoma from the IGNYTE clinical trial
Michael K. K. Wong (Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA) reported three-year survival data from the IGNYTE trial of vusolimogene oderparepvec (RP1), an HSV1-based oncolytic immunotherapy expressing GM-CSF and a fusogenic glycoprotein (GALV-GP-R) in combination with nivolumab for patients with advanced melanoma that progressed on anti-PD-1 therapy. 140 patients with advanced melanoma with prior anti-PD-1 failure received nivolumab and intratumoral injections of RP1. 55.7% of patients were PD-L1 negative (< 1%), 46.5% of patients had prior anti-CTLA-4 therapy, and 65% of patients exhibited primary resistance to anti-PD-1 therapy. Previous reports of the IGNYTE trial indicated an objective response rate of 33.6%, a 16.4% complete response rate, and median duration of response was 24.8 months. In overall patient population, median age was 62, 67.9% (95) were males and 49.3% (69) had Stage IVM1b/c/d disease with 55.7% (78) having PD-L1 negative tumors. Amongst prior therapies, 65 patients (46.5%) had received anti-CTLA4 treatments. Median progression-free survival was 3.6 months for the entire patient population and 34.9 months for responders. Median overall survival (OS) among all patients was 32.9 months, and the 3-year OS rate was 47.8%. Median OS among responders was not reached and 18.5 months for non-responders, and 3-year OS rates were 83.5% and 26.4% respectively. OS benefits were observed in all patient subgroups examined, except for patients with prior anti-CTLA-4 treatment. No new safety signals were observed. RP1 combined with nivolumab is associated with deep and durable responses that translate into long-term clinical benefits, including extended survival, for patients with anti-PD-1-failed melanoma.
For more information on how RP1 remodels the tumor immune microenvironment, read this article by Roulstone et al in JITC.
Investigational off-the-shelf therapeutic cancer vaccine IO102-IO103 combined with nivolumab and relatlimab for unresectable melanoma
9519. A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma
James W. Smithy (Memorial Sloan Kettering Cancer Center, New York, NY, USA) presented clinical results and analyses of T cell expansion from a multicenter phase 2 trial of subcutaneous IO102-IO103 combined with intravenous nivolumab-relatlimab (nivo-rela) in patients with unresectable, previously untreated non-uveal melanoma. IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine that activates and expands T cells that target cells expressing the immunosuppressive proteins IDO1 and/or PD-L1. Prior clinical studies have shown that IO102-IO103 combined with pembrolizumab numerically improved progression free survival (PFS) for advanced melanoma, compared to pembrolizumab alone, but the efficacy and safety of IO102-IO103 with combination of nivo-rela is unknown. 43 patients with previously untreated, unresectable melanoma were enrolled in the study. 36% of patients were PD-L1 positive. For the overall patient population, the unconfirmed objective response rate (uORR) was 60%, and the confirmed objective response rate (cORR) was 53%. 10 patients achieved a complete response, and 16 patients obtained a partial response. uORR for PD-L1-negative patients (n=25) was 52% and 79% for PD-L1-positive patients (n=14). At a median follow-up of 12 months, median progression-free survival (PFS) was 8.1 months, with a 12-month PFS rate of 47%. Among PD-L1-negative patients, median PFS was 8.1 months, compared to 24 months for PD-L1-positive patients (12-month PFS 43% and 60%, respectively). The median duration of response (DOR) was not reached, and 12-month DOR rate was 77%. IO102-IO103 was well tolerated. The most common treatment-related adverse event (TRAE) was injection site reactions, which occurred in 70% of patients. Six patients (14%) experienced at least one TRAE of grade 3 or higher, and 8 patients discontinued therapy due to toxicity. Patients with radiographic responses to IO102-IO103 with nivo-rela exhibited higher levels of peripheral T cell clonality at baseline and at weeks 4 and 8 of treatment, and radiographic response was also associated with greater expansion of de novo peripheral T cell clones that were not present at baseline. With a confirmed objective response rate of 53%, durable responses, and manageable safety profile, IO102-IO103 in combination with nivo-rela exceeds historic response rates of nivo-rela alone, justifying further investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma.