IDO-derived peptide vaccine/PD-L1-derived peptide vaccine(Herlev Hospital)

Patients who received IO Biotech's vaccine with Keytruda experienced median progression-free survival of 6.6 months and a disease control rate of 66.7%. Immune checkpoint inhibitors are the superheroes of cancer therapy. Drugs like Bristol Myers Squibb’s Opdivo and Merck’s Keytruda are among the most profitable in the world—Keytruda pulled in $25 billion last year, making it the bestselling drug of 2023. But every good superhero needs a sidekick.During the 2024 European Society for Medical Oncology congress, Copenhagen-based IO Biotech presented data showing that its IO102-IO103 cancer vaccine, in combination with Keytruda (pembrolizumab), delivered an objective response rate of 44.4%, hitting the primary endpoint of a phase 2 trial in patients with advanced squamous cell carcinoma of the head and neck (SCCHN).“With the data we’ve presented from studies in head and neck cancer and in melanoma, evidence is accumulating that the combination of IO102-IO103 with the anti-PD-1 therapy pembrolizumab could be a safe and efficacious first-line treatment for patients with a range of cancers, including those with metastatic and difficult-to-treat disease,” IO Biotech's chief medical officer, Qasim Ahmad, M.D., said in a Sept. 14 release. IO Biotech’s IO102-IO103 vaccine is actually a combination of two vaccines that each prime patients’ T cells to target tumors. IO102 induces the immune cells to go after indoleamine-2,3-dioxygenase (IDO), an enzyme found inside of cells, while IO103 directs them toward programmed death-ligand 1 (PD-L1), a protein embedded in the cell membrane. Both IDO and PD-L1 are used by cancer cells to avoid being targeted and destroyed by the body’s immune system.By activating T cells against IDO and PD-L1, the theory is that the body’s immune system will join the fight against cancerous cells.The IOB-022/KN-D38 phase 2 trial had a total of 63 patients enrolled across cancer types as of Aug. 2, with 21 SCCHN patients enrolled. SCCHN patients who received the vaccine with Keytruda experienced median progression-free survival of 6.6 months and a disease control rate of 66.7%.Adverse events were common, with 20 of 21 patients experiencing side effects. Most were of low severity, like rash, fatigue and a reaction at the injection site. One patient suffered a severe treatment-related adverse event, immune thrombocytopenia, which was managed with corticosteroid treatment. Two patients discontinued treatment due to side effects of conjunctivitis and colitis, while another died of an unrelated illness during the trial. That left 18 patients for the data analysis.Data from the cohort of patients with non-small cell lung cancer will be presented at another meeting this fall, IO Biotech said in the release.Merck is collaborating on the IO102-IO103 trials, but IO Biotech maintains global commercial rights to the vaccines, according to the release. IO’s assets aren’t the only cancer vaccines Merck is auditioning for a supporting role alongside Keytruda. At the American Society of Clinical Oncology meeting in June, the Big Pharma shared data from a phase 2 trial of an mRNA vaccine being developed with Moderna. At a typical follow-up of 34.9 months, the vaccine and Keytruda combo reduced the risk of recurrence or death by 49% compared to Keytruda alone in patients with resected melanoma.IO Biotech raised a $155 million series B in 2021 to advance its cancer vaccines. The Danish company is also testing IO102-IO103 in combination with Opdivo (nivolumab) and BMS' relatlimab in a phase 2 trial in untreated, unresectable melanoma. The vaccine-Opdivo combo received a breakthrough-therapy designation from the FDA in 2020.Earlier this year at the World Vaccine Congress, Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, expressed the agency’s willingness to review new cancer vaccines.

- Based on a per-protocol interim analysis of safety and efficacy data, the Independent Data Monitoring Committee (IDMC) recommended that the trial continue without modifications - No new safety signals observed at interim analysis - Primary endpoint of progression free survival projected to be reached in the first half of 2025 Aug. 30, 2024 -- IO Biotech (Nasdaq: IOBT), a clinical-stage biopharmaceutical company developing novel, off-the-shelf, immune-modulating therapeutic cancer vaccines based on its T-win® platform, today announced that an Independent Data Monitoring Committee (IDMC) recommended continuation of the company’s pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) of its lead investigational therapeutic vaccine, IO102-IO103, following a per-protocol interim analysis. The trial is evaluating IO102-IO103 in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, as a first-line treatment for patients with unresectable or metastatic (advanced) melanoma. Based on their review of the safety and efficacy data, the IDMC recommended that the trial continue without modifications and noted that no new safety signals were observed. The primary endpoint of progression-free survival (PFS) is projected to be reached in the first half of 2025. The per-protocol interim analysis was performed one year after 225 patients were randomized in the trial. The interim efficacy analysis was intentionally set with a high statistical bar (p≤0.005), and based on the analysis, the IDMC determined that the data did not meet the criteria to declare superiority of ORR. The trial was designed to preserve most of the statistical alpha for the trial’s primary endpoint of PFS. The PFS analysis is event-driven and will be conducted when 226 events (disease progression or death) have been reported in the trial with independent central review. With 407 patients randomized, the trial is powered at 89% to detect a 35% reduction in the risk of an event. “To date, none of the approved immunotherapeutic combinations for the treatment of advanced melanoma demonstrated statistical significance in ORR in large Phase 3 trials; nevertheless, these trials achieved statistical significance on PFS,” said Mai-Britt Zocca, PhD, President and CEO of IO Biotech. “Based on the 25.5 months median PFS we observed in the Phase 1/2 trial of IO102-IO103 in combination with a PD-1 inhibitor in advanced melanoma, with no added significant systemic toxicity than that typically seen with anti-PD-1 monotherapy, we remain optimistic about meeting the primary endpoint of PFS, projected to occur in the first half of 2025.” Igor Puzanov, MD, MSCI, FACP, Director, Center for Early Phase Clinical Trials, Chief, Division of Melanoma, Department of Medicine and Investigator for the Phase 3 Study at Roswell Park Comprehensive Cancer Center, Buffalo, New York commented, “The incidence of melanoma is on the rise and new treatments are needed. This is a novel investigational immune-modulatory therapeutic cancer vaccine combined with an anti-PD-1 therapy that has the potential to transform the treatment paradigm with a new and better option for people battling advanced melanoma. I am eagerly awaiting the PFS primary endpoint readout of this Phase 3 trial that could further validate this novel cancer vaccine’s ability to help patients with advanced melanoma who are seeking more efficacious, low treatment-induced toxicity therapy options.” Jessica Hassel, MD, Head of the Section for Dermato-Oncology at the University Hospital Heidelberg, investigator and lead enroller for the Phase 3 trial added, “We have been seeing promising results using combination immunotherapeutic treatments and I remain confident that IO102-IO103 in combination with pembrolizumab could offer new hope for treating patients with advanced melanoma. I look forward to the full readout of data at the end of this trial to further understand the full potential of this investigational therapeutic cancer vaccine combined with an anti-PD-1 agent.” Dr. Zocca continued, “We continue to be enthusiastic about the encouraging preliminary data from our Phase 2 basket trial evaluating IO102-IO103 in combination with pembrolizumab for the treatment of metastatic non-small cell lung cancer (NSCLC) or recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). Data from the SCCHN cohort has been accepted for poster presentation at the ESMO congress, and data from the NSCLC cohort has been accepted to another medical meeting in the fall. We believe these data could provide further evidence to support the broader potential of therapeutic cancer vaccines for the benefit of patients in additional cancer indications.” IOB-013/KN-D18 (Clinical Trials.gov: NCT05155254) is an open label, randomized Phase 3 pivotal clinical trial of IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated, unresectable or metastatic (advanced) melanoma. A total of 407 patients have been enrolled from more than 100 centers across the United States, Europe, Australia, Turkey, Israel and South Africa. The primary endpoint of the study is progression-free survival, an event-driven analysis conducted when 226 events, defined as disease progression or death, have been reported in the study. Secondary endpoints include overall response rate (ORR), overall survival (OS), durable objective response (DRR), complete response rate (CRR), duration of response (DoR), time to complete response (TTCR), disease control rate (DCR), and incidence of AEs and SAEs (safety and tolerability). Biomarkers in the blood and tumor tissue will also be assessed. IO Biotech is sponsoring the Phase 3 trial and Merck is supplying pembrolizumab. IO102-IO103 is an investigational off-the-shelf therapeutic cancer vaccine designed to kill both tumor cells and immune-suppressive cells in the tumor microenvironment (TME) by stimulating activation and expansion of T cells against indoleamine 2,3-dioxygenase (IDO) positive and/or programmed death-ligand 1 (PD-L1) positive cells. The company is currently conducting a pivotal Phase 3 trial (IOB-013/KN-D18; NCT05155254) investigating IO102-IO103 in combination with pembrolizumab versus pembrolizumab alone in patients with advanced melanoma, a Phase 2 basket trial (IOB-022/KN-D38; NCT05077709) investigating IO102-IO103 in combination with pembrolizumab as first line treatment in patients with solid tumors, and a Phase 2 basket trial (IOB-032/PN-E40; NCT05280314) investigating IO102-IO103 in combination with pembrolizumab as neo-adjuvant/adjuvant treatment of patients with solid tumors. The clinical trials are sponsored by IO Biotech and conducted in collaboration with Merck, which is supplying pembrolizumab. IO Biotech maintains global commercial rights to IO102-IO103. KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating therapeutic cancer vaccines based on its T-win® platform. The T-win platform is based on a novel approach to cancer vaccines designed to activate T cells to target the immunosuppressive cells in the tumor microenvironment. IO Biotech is advancing its lead cancer vaccine candidate, IO102-IO103, in clinical trials, and additional pipeline candidates through preclinical development. Based on positive Phase 1/2 first line metastatic melanoma data, IO102-IO103, in combination with pembrolizumab, has been granted a breakthrough therapy designation for the treatment of advanced melanoma by the US Food and Drug Administration. IO Biotech is headquartered in Copenhagen, Denmark and has US headquarters in New York, New York. The content above comes from the network. if any infringement, please contact us to modify.