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

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) 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

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

IO Biotech Announces Clinical Improvement in Progression Free Survival Demonstrated in Pivotal Phase 3 Trial of Cylembio plus KEYTRUDA (Pembrolizumab) for the Treatment of First-line Advanced Melanoma, but Statistical Significance Narrowly Missed (The Manila Times) - "The early and sustained separation of PFS curves demonstrated an improvement with a hazard ratio of 0.77 [95% CI: 0.58-1.00; p=0.056; threshold for significance p≤0.045]...Although not yet mature, a trend toward an improvement in overall survival was also observed [HR 0.79 (95% CI: 0.57-1.10)]; the company expects OS to mature over the next six to nine months...The combination was well tolerated, with no new safety signals observed...Based on these results, IO Biotech plans to meet with the United States (US) Food and Drug Administration (FDA) this fall to discuss the totality of data and determine next steps for submission of a Biologics License Application (BLA) for the treatment of advanced melanoma."

P3 data • Melanoma

IO Biotech Stock Slumps After Trial Of Cancer Therapy Plus Keytruda Misses Study Goal: Retail Sees Shares Rise 10x (Investing.com) - "IOBT stock traded over 19% lower on Monday morning, at the time of writing....Another opined that the stock price should multiply by 10 times in the aftermath of the data release."

P3 data • Stock price • Melanoma

IO Biotech Reports First Quarter 2025 Financial Results and Business Highlights (GlobeNewswire) - "The company’s pivotal Phase 3 trial (IOB-013/KN-D18) is progressing as planned with the readout of the primary endpoint of progression free survival (PFS) still expected in the third quarter of 2025....The company continues to plan to submit a BLA to the U.S. Food & Drug Administration (FDA) in 2025 for Cylembio and, subject to FDA approval, launch a potentially first-in-class therapeutic cancer vaccine for patients with advanced melanoma in the US in 2026....The company expects initial data from the perioperative...Phase 2 solid tumor basket trial (IOB-032/PN-E40)...as well as longer-term data from the company’s other ongoing Phase 2 basket trial, IOB-022/KN-D38, in patients with advanced SCCHN or non-small cell lung cancer (NSCLC) in the second half of 2025."

Clinical data • FDA filing • Launch US • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck

IO Biotech Presents New Data at AACR 2025 Supporting Dual Mechanism and Immune Activation of Cancer Vaccines IO102-IO103 and IO170 (GlobeNewswire) - "Poster Highlights: IO102-IO103, a dual-antigen vaccine targeting IDO1+ and PD-L1+ cells, generated strong T-cell responses and modulated the tumor microenvironment in two mouse models, where IDO1 and PD-L1 vaccine each contributed differently to control tumor growth. Gene expression profiling also showed that the vaccine triggered unique molecular changes not seen with PD-1 or PD-L1 inhibitors, indicating a potentially synergistic mechanism. (Abstract #2241); IO170, also developed using IO Biotech’s T-win platform, demonstrated significant tumor growth inhibition in breast and prostate cancer mouse models. The TGF- β-directed vaccine led to infiltration of vaccine-specific T cells with increased density of CD8+ T-cells in the tumor and reshaped the tumor microenvironment to favor immune activation. Spatial analysis in prostate tumors showed increased cytotoxic immune regions and reduced levels of suppressive cells like M2 macrophages. (Abstract #2257)."

Preclinical • Breast Cancer • Prostate Cancer

IO Biotech Showcases Scientific Leadership Through Cancer Vaccines Educational Session at the American Association for Cancer Research (AACR) Annual Meeting 2025 (GlobeNewswire) - "IO Biotech...announced that one of its scientific co-founders, Mads Hald Andersen, DMSc, PhD, Director of the National Center for Cancer Immune Therapy (CCIT-DK), chaired and presented at an educational session on cancer vaccines at the 2025 American Association for Cancer Research (AACR) Annual Meeting....Dr. Andersen delivered the presentation on IMVs, a new class of therapeutic cancer vaccines that reshape the tumor microenvironment (TME). His talk highlighted the dual mechanism of action of the most clinically advanced immune modulatory therapeutic cancer vaccine, IO102-IO103 (developed by IO Biotech), which targets both tumor cells and the host immune suppressive cells by stimulating activation and expansion of T cells against IDO+ and PDL1+ cells."

Clinical • Oncology

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

IO Biotech Announces Acceptance of Abstracts to be Presented at the 2025 American Association for Cancer Research (AACR) Annual Meeting (GlobeNewswire) - "IO Biotech...announced that two abstracts have been accepted for presentation at the American Association for Cancer Research (AACR) Annual Meeting 2025....New non-clinical data strengthens evidence of contributions of IO102 and IO103 to tumor growth control through target specific T-cell activation, offering a distinct and complementary approach to checkpoint inhibitors. New preclinical data for IO170 add to growing body of evidence supporting the potential of immune-modulatory therapeutic cancer vaccines to treat a wide range of cancers."

Preclinical • Solid Tumor

IO Biotech Reports 2024 Business Highlights (GlobeNewswire) - "The company’s Phase 3 pivotal trial (IOB-013/KN-D18), which is evaluating Cylembio...in advanced melanoma, is ongoing....The rate of PFS events has slowed in the study, and as such, the company now expects the readout of the PFS primary endpoint in third quarter of 2025. The company continues to plan to submit a BLA to the FDA in 2025 for Cylembio and, subject to FDA approval, launch its first therapeutic cancer vaccine in the US in 2026 for patients with advanced melanoma."

FDA filing • Launch US • P3 data • Melanoma

IO Biotech Reports 2024 Business Highlights (GlobeNewswire) - "The company continues to progress clinical development of Cylembio in its perioperative Phase 2 solid tumor basket trial (IOB-032/PN-E40)....In this trial, patients with resectable melanoma or squamous cell carcinoma of the head and neck (SCCHN) are dosed before (neo-adjuvant) and after (adjuvant) surgery with curative intent. The company expects initial data from this trial in the second half of 2025....Patients in...IOB-022/KN-D38...basket trial will continue to be followed, with longer-term data expected in the second half of 2025....The company adopted Cylembio (imsapepimut and etimupepimut, adjuvant) as the US brand name for its IO102-IO103 lead investigational therapeutic cancer vaccine."

Commercial • P2 data • Bladder Cancer • Melanoma • Non Small Cell Lung Cancer • Squamous Cell Carcinoma of Head and Neck • Urothelial Cancer

Combination Therapy With Nivolumab and PD-L1/IDO Peptide Vaccine to Patients With Metastatic Melanoma (clinicaltrials.gov) - P1/2 | N=48 | Completed | Sponsor: Inge Marie Svane | Recruiting ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor

IO Biotech Completes Enrollment in Phase 2 Trial of its Investigational, Off-the-shelf Therapeutic Cancer Vaccine, IO102-IO103, as Neoadjuvant/Adjuvant Treatment for Patients with Resectable Melanoma or Head and Neck Cancer (GlobeNewswire) - "IO Biotech...completed enrollment in its neoadjuvant/adjuvant Phase 2 basket trial (IOB-032/PN-E40). The trial is studying IO102-IO103, the company’s lead investigational therapeutic cancer vaccine candidate, in combination with Merck’s (known as MSD outside of the US and Canada) anti-PD-1 therapy, KEYTRUDA (pembrolizumab), given before (neoadjuvant) and after (adjuvant) surgery with curative intent in patients with resectable melanoma or squamous cell carcinoma of the head and neck (SCCHN)....initial data from this Phase 2 basket trial also expected in 2025, we hope to add to the accumulating evidence of potential benefit of this combination therapy across a range of difficult-to-treat cancers."

Enrollment closed • P2 data • Head and Neck Cancer • Melanoma

IO Biotech secures up to €57.5 million in debt financing from the European Investment Bank (GlobeNewswire) - "IO Biotech...announced that it has entered into a loan facility of up to €57.5 million from the European Investment Bank (EIB), the long-term lending institution of the European Union owned by its Member States...The company expects the first two tranches to be available for disbursement in the first quarter of 2025...'The support from the EIB, which is provided on favorable terms, will help fund the continued development and pre-commercialization of IO102-IO103 and other therapeutic cancer vaccine candidates generated from our T-Win platform.'....The company has 36 months to satisfy the conditions for Tranche C, which include raising an additional $50 million in cash and submitting an application for marketing authorization for IO102-IO103 in the U.S. or the EU."

Financing • Solid Tumor

A phase 2 trial of the IO102-IO103 cancer vaccine plus pembrolizumab: results from the first-line (1L) cohort of PD-L1 high metastatic non-small cell lung cancer (NSCLC) (SITC 2024) - P2 | "Results from a phase 1/2 trial of anti-PD1 naïve metastatic melanoma patients treated with IO102-IO103/nivolumab demonstrated deep and durable responses with 25.5 months as median progression-free survival (PFS); treatment was well tolerated. Longer follow-up for PFS and duration of response, along with exploratory biomarkers are planned to be presented at the meeting. Ethics Approval USA: WCG • IRB00000533 o 0101 – UC Davis o 0102 – Mid Florida o 0105 – City of Hope o 0108 – UC San Diego o 0111 – UPenn o 0112 – VCS 0103 – Univ of Toledo • The University of Toledo Human Research Protection Program Biomedical IRB • IRB number: 301251 • FWA00010686 0106 – Montefiore • Brany IRB • IRB#00000080 0107 – OHSU • OHSU IRB • IRB00000471 • FWA00000161 0113 – Johns Hopkins • Office of Human Subjects Research IRB • IRB00370966 • FWA00005752 (JH University School of Medicine) • FWA00006087 (JH Health System and JH Hospital) UK: • Name of EC: London - Westminster Research..."

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

IO Biotech Reports Third Quarter 2024 Financial Results and Provides Business Highlights (GlobeNewswire) - "As we look to the primary endpoint data readout from our Phase 3 pivotal trial in the first half of next year, we plan to be prepared to submit a Biologics License Application (BLA) to the FDA in 2025 and potentially make our first therapeutic cancer vaccine available for patients in the US with advanced melanoma in 2026....We are excited about the strength of the data supporting the potential of IO112 and plan to submit an Investigational New Drug (IND) application to the FDA for this program in 2025."

FDA filing • IND • Launch US • P3 data • Melanoma • Solid Tumor

IO Biotech Reports its Off-the-Shelf Therapeutic Cancer Vaccine, IO102-IO103, in Combination with KEYTRUDA Demonstrates Promising Activity and Durability in First-line Treatment of Patients with Metastatic Lung Cancer in Phase 2 IOB-022 Study (GlobeNewswire) - P2 | N=63 | NCT05077709 | Sponsor: IO Biotech | "The data from 31 efficacy evaluable patients demonstrated: A 55% unconfirmed (16 partial responses, 1 complete response), 48% confirmed overall response rate (ORR) in a PD-L1 high population of patients with NSCLC; An 81% disease control rate (DCR); No disease progression at 12 months in approximately 50% of patients; An encouraging 8.1-month median progression-free survival (PFS); Median duration of response (DOR) not yet reached; A safety profile consistent with previously reported data when combining IO102-IO103 with anti-PD-1 monotherapy."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor