Cylembio (imsapepimut and etimupepimut, adjuvanted) / IO Biotech - LARVOL DELTA

KIEO: Neoadjuvant Pembrolizumab and IO102-103 for Squamous Cell Carcinoma of the Head and Neck (SCCHN). (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting ➔ Active, not recruiting

Enrollment closed • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

A phase 2 trial of IO102-IO103 and nivolumab-relatlimab in previously untreated, unresectable melanoma. (ASCO 2026) - P2 | "IO102-IO103 in combination with nivo-rela was associated with a higher objective response rate compared to historical data for nivo-rela alone, meeting the trial's primary endpoint. No unexpected safety signals were observed. These findings support the further clinical investigation of IO102-IO103 with nivo-rela as an initial treatment for unresectable melanoma."

IO biomarker • P2 data • Acute Kidney Injury • CNS Disorders • Endocrine Disorders • Eye Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Melanoma • Myositis • Nephrology • Neutropenia • Renal Disease • Solid Tumor • PD-L1

Neoadjuvant Immunotherapy for Head and Neck Squamous Cell Carcinoma: Treatment Response, Complications, and De-escalation (AAO-HNSF 2026) - "Regimens included cemiplimab (29%), pembrolizumab/carboplatin/paclitaxel (19%), nivolumab (19%), 5-azacytidine/nivolumab (13%), or IO102-IO103 vaccine/pembrolizumab (13%). Neo-IO demonstrated substantial clinical and pathologic responses in patients with head and neck SCC, with a subset achieving CR without surgery. These preliminary data support future investigation into treatment de-escalation and multivariable analyses by regimen and tumor subtype."

Clinical • Endocrine Disorders • Head and Neck Cancer • Hepatology • Nephrology • Oncology • Pulmonary Embolism • Renal Disease • Respiratory Diseases • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) advanced melanoma: Primary phase III results (IOB-013/KN-D18) (ESMO 2025) - P3 | "Combination was safe and well tolerated. The data support the potential benefit of this combination in advanced melanoma, without adding significant systemic toxicity."

Clinical • Late-breaking abstract • Metastases • P3 data • Melanoma • Oncology • Solid Tumor • IDO1 • PD-L1

IDO and PD-L1 Peptide Based Immune-Modulatory Therapeutic (IO102-IO103) in Combination With Pembrolizumab for BCG-Unresponsive or Intolerant, Non-Muscle Invasive Bladder Cancer (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: University of California, Davis | Recruiting ➔ Active, not recruiting | N=30 ➔ 6

Enrollment change • Enrollment closed • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer

YIA26-003: Characterizing the Peripheral T-Cell Repertoire in Patients With Unresectable Melanoma Treated With the IDO- and PD-L1 Targeted Peptide Vaccine IO102-IO103 and Nivolumab-Relatlimab Fixed-Dose Combination. (PubMed, J Natl Compr Canc Netw) - No abstract available

Journal • Melanoma • Oncology • Solid Tumor • PD-L1

IOB-032/PN-E40: A phase 2 study of neoadjuvant/adjuvant IO102-IO103 cancer vaccine plus pembrolizumab in resectable HNSCC (AACR 2026) - P2 | "The regimen was well-tolerated, and the implementation of neoadjuvant dosing and pathological assessment was feasible. Further follow-up will provide key insights into the potential benefit of adding IO102-IO103 to perioperative treatment with pembro."

Clinical • P2 data • Head and Neck Cancer • Oncology • Oropharyngeal Cancer • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IDO1 • PD-L1

KEYNOTE-D38: IO102-IO103 in Combination With Pembrolizumab as First-line Treatment for Patients With Metastatic NSCLC, SCCHN, or mUBC (clinicaltrials.gov) - P2 | N=63 | Completed | Sponsor: IO Biotech | Active, not recruiting ➔ Completed | Trial completion date: Nov 2024 ➔ Feb 2026 | Trial primary completion date: Jan 2024 ➔ Nov 2025

Pan tumor • Trial completion • Trial completion date • Trial primary completion date • Bladder Cancer • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer • PD-L1

IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma. (PubMed, Ann Oncol) - "IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma."

IO biomarker • Journal • Melanoma • Oncology • Solid Tumor • BRAF • IDO1 • PD-L1

Immune-modulatory therapeutic cancer vaccines against IDO1 and PD-L1 control tumor growth through target specific changes in the tumor microenvironment (AACR 2025) - "The development of immune-modulatory vaccines against IDO1+ and PD-L1+ immune suppressive and/or tumor cells in the TME (IO102-IO103) has revealed promising clinical results1 and is now being investigated in a Phase 3 clinical trial in advanced melanoma...The gene expression changes observed were different from the signatures of anti-PD-L1 and anti-PD1, suggesting a complementary mode of action to those therapeutics. Altogether, our data support the clinical potential of IDO1 and PD-L1 immune-modulatory vaccines to improve existing therapeutics in cancer."

Biomarker • IO biomarker • Tumor microenvironment • Melanoma • Oncology • Solid Tumor • CD8 • IDO1 • IFNG • PD-L1 • TNFA

Immune modulatory cancer vaccines against IDO1 and PD-L1 trigger distinct pathways and cooperatively reduce tumor growth in preclinical models (AACR 2024) - "Lastly, IDO1 and PDL1-specific CD4+ T cell clones from melanoma patients treated with IO102-IO103 vaccine could selectively target cells differentially expressing IDO1 or PDL1.Our data collectively show that cells expressing IDO1 and PD-L1 represent distinct populations in the TME thus targetable by the IDO1-PD-L1 vaccination approach...These data are supported by ex vivo functional assays using target specific T cells from vaccinated patients. Altogether, our data support the use of a dual antigen approach to reduce the immunosuppression and enhance anti-tumor effect."

IO biomarker • Preclinical • Melanoma • Oncology • Solid Tumor • CD4 • IDO1 • IFNG • PD-L1

YIA26-003: Characterizing the Peripheral T-Cell Repertoire in Patients With Unresectable Melanoma Treated With the IDO- and PD-L1 Targeted Peptide Vaccine IO102-IO103 and Nivolumab-Relatlimab Fixed-Dose Combination. (PubMed, J Natl Compr Canc Netw) - No abstract available

Journal • Melanoma • Oncology • Solid Tumor • PD-L1

Characterizing the Peripheral T-Cell Repertoire in Patients With Unresectable Melanoma Treated With the IDO- and PD-L1 Targeted Peptide Vaccine IO102-IO103 and Nivolumab-Relatlimab Fixed-Dose Combination (NCCN 2026) - P2 | "This work was funded by the NCCN Foundation®. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of National Comprehensive Cancer Network® (NCCN®) or the NCCN Foundation."

Clinical • IO biomarker • Melanoma • Solid Tumor • PD-L1

KIEO: Neoadjuvant Pembrolizumab and IO102-103 for Squamous Cell Carcinoma of the Head and Neck (SCCHN). (clinicaltrials.gov) - P2 | N=30 | Recruiting | Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=15 ➔ 30

Enrollment change • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Activity and Safety of Peptide-based Immunotherapy in Patients With Squamous Cell Carcinoma of the Head and Neck. (clinicaltrials.gov) - P2 | N=17 | Terminated | Sponsor: Cliniques universitaires Saint-Luc- Université Catholique de Louvain | Trial completion date: Jun 2024 ➔ Mar 2025 | Recruiting ➔ Terminated; unmet primary endpoint

Trial completion date • Trial termination • Head and Neck Cancer • Hypopharyngeal Cancer • Laryngeal Cancer • Oncology • Oral Cancer • Oropharyngeal Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

IO Biotech Announces Publication of Five-year Clinical Outcomes of Phase 1/2 Trial in Nature Communications (GlobeNewswire) - "The MM1636 results published today showed the five-year follow-up analysis of IO102-IO103 in combination with nivolumab in patients with metastatic melanoma, demonstrating durable clinical activity with a 25.5-month median progression-free survival (PFS). The results also showed the identification of potential vaccine-specific immune biomarkers of long-term benefit, not observed in a matched anti-PD-1 monotherapy cohort, suggesting a distinct vaccine-induced immune modulation increasing anti-tumor activity."

P1/2 data • Melanoma

A Study of IO102/IO103, Nivolumab, and Relatlimab in People With Melanoma (clinicaltrials.gov) - P2 | N=43 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Recruiting ➔ Active, not recruiting

Enrollment closed • Melanoma • Oncology • Solid Tumor • BRAF

On November 18, 2025, IO Biotech, Inc. presented updated results from its Phase 3 trial of Cylembio at the Jefferies Global Healthcare Conference. (TradingView) - "Cylembio showed improved progression-free survival in advanced melanoma. Median PFS was 19.4 months with Cylembio vs. 11.0 months with pembrolizumab alone. Trial results indicated no significant added systemic toxicity with Cylembio....Plans to align on new Phase 3 design with FDA and discuss EU submissions."

P3 data • Melanoma

Meeting scheduled with FDA in December to align on the design of a potential new Phase 3 registrational trial for IO102-IO103 in patients with advanced melanoma (GlobeNewswire)

New P3 trial • Melanoma

IO102-IO103 cancer vaccine plus pembrolizumab for first-line (1L) treatment of advanced solid tumors: Final results of a phase II basket trial (ESMO 2025) - P2 | "Table: 1557P Efficacy outcomes in patients with NSCLC and SCCHN, in the efficacy-evaluable population NSCLC N=31 SCCHN N=18 Median FU, months 21.4 18.0 ORR by RECIST 1.1 48% 44% Median PFS, months (95% CI) 8.1 (4.2, 16.6) 7.0 (2.0, 13.1) PFS at 12 months, % (95% CI) 48.4 (30.2, 64.4) 33.3 (13.7, 54.5) OS at 12 months, % (95% CI) 77.2 (58.0, 88.4) 66.7 (40.4, 83.4) CI, confidence interval; FU, follow-up; OS, overall survival; PFS, progression-free survival Conclusions These data build on the encouraging clinical evidence reported earlier, of IO102-IO103 in combination with anti-PD1 therapy, as 1L treatment in several tumor types. Landmark PFS and OS, including at 18 months, updated safety and exploratory biomarkers will be presented at the meeting."

Clinical • IO biomarker • Metastases • P2 data • Pan tumor • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • IDO1 • PD-L1

Phase 2 Basket Trial in NSCLC and SCCHN (GlobeNewswire) - "Among 49 efficacy-evaluable patients (31 with NSCLC and 18 with SCCHN), mPFS was 8.1 months at 21.4 months of follow-up in NSCLC and 7.0 months at 18 months of follow-up in SCCHN, with durable responses and encouraging 18-month overall survival (OS) rates. The combination’s safety profile remained consistent with anti–PD-1 monotherapy, with no new safety signals."

P2 data • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

IO Biotech Presents Phase 3 Results for Cylembio plus KEYTRUDA (pembrolizumab) in First-line Advanced Melanoma at ESMO 2025 (GlobeNewswire) - "In the randomized Phase 3 trial, 407 patients with previously untreated advanced melanoma received either Cylembio plus pembrolizumab or pembrolizumab alone. Median progression-free survival was 19.4 months for the combination and 11.0 months for pembrolizumab (hazard ratio [HR] 0.77; 95% CI, 0.58–1.00; p=0.0558), narrowly missing the primary endpoint prespecified threshold for statistical significance (p≤0.045)....Across virtually all subgroups, outcomes in progression-free survival consistently favored the combination regimen, including among patients with PD-L1–negative tumors (16.6 vs 3.0 months; HR 0.54; 95% CI, 0.35-0.85), BRAFV600 mutated tumors (HR 0.60; 95% CI, 0.40-0.90), and elevated LDH (HR 0.60; 95% CI, 0.39-0.92)."

P3 data • Melanoma

IO Biotech Provides Update Following Pre-BLA Meeting with FDA (IO Biotech Press Release) - "The FDA has recommended that IO Biotech not submit a BLA based on the data from the IOB-013 clinical trial. As previously announced, in the IOB-013 trial, treatment with Cylembio plus pembrolizumab improved progression free survival (PFS), however the results narrowly missed statistical significance. The company plans to continue the dialogue with FDA to align on the design of a potential new registrational study for Cylembio."

FDA event • Melanoma

IO Biotech Announces Late-Breaking Abstract in Advanced Melanoma Selected for Oral Presentation at ESMO Congress 2025 (GlobeNewswire) - "The oral presentation will highlight the results from the randomized Phase 3 trial assessing the efficacy and safety of IO102-IO103 (IDO/PD-L1 vaccine) in combination with pembrolizumab vs pembrolizumab monotherapy in 1L advanced melanoma. In addition, final data from the Phase 2 basket trial with updated efficacy and safety data, median progression-free survival (PFS), landmark PFS and overall survival data, as well as biomarker and translational data for 1L treatment in non-small cell lung cancer (NSCLC) and squamous cell carcinoma of head and neck (SCCHN), will be presented in a poster session."

Late-breaking abstract • P2 data • P3 data • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

IO Biotech to Announce Topline Results of Pivotal Phase 3 Trial of Cylembio in Combination with KEYTRUDA (pembrolizumab) as a First-Line Treatment for Patients with Advanced Melanoma (GlobeNewswire) - "IO Biotech...announced the company will hold a conference call and webcast on Monday, August 11, 2025, at 8:30 AM ET to disclose the topline results of the pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) of its investigational, immune-modulatory, off-the-shelf therapeutic cancer vaccine, Cylembio (imsapepimut and etimupepimut, adjuvant) in combination with pembrolizumab vs. pembrolizumab alone as a first-line treatment for unresectable or metastatic (advanced) melanoma."

P3 data: top line • Melanoma