{"entity":{"id":"idea-cost-low-dose-immunotherapy-trials","kind":"idea","name":"Test one-tenth-dose immunotherapy where the full dose is unaffordable","aka":[],"tldr":"A randomised trial at Tata Memorial added nivolumab at 20 mg every three weeks, about one-twelfth of the standard dose, to cheap metronomic chemotherapy for head and neck cancer patients who could not afford full-dose immunotherapy, and they lived longer. Checkpoint inhibitors saturate their target far below approved doses, so publicly funded trials should test low doses in common cancers.","summary":"Patil et al. (JCO 2023) randomised 151 patients with advanced head and neck cancer to triple metronomic chemotherapy with or without nivolumab 20 mg flat dose every three weeks, about one-twelfth of the standard dose. One-year overall survival was 43.4% versus 16.3%. Checkpoint inhibitors saturate their target at doses far below those approved, which were chosen for development convenience rather than minimum effective exposure. Publicly funded non-inferiority trials of low-dose pembrolizumab and nivolumab in common indications would establish whether the finding generalises.","asOf":"2026-09-10","links":[{"label":"Patil et al., JCO 2023: low-dose nivolumab with metronomic chemotherapy","url":"https://doi.org/10.1200/JCO.22.01015"}],"tags":[],"related":[],"cancers":["head-and-neck"],"sections":["immunotherapy"],"technologies":["checkpoint-inhibitor"],"targets":[],"drugs":["nivolumab","pembrolizumab"],"companies":[],"institutions":["tata-memorial"],"pathways":[],"terms":["project-optimus"],"trials":["checkmate-141","keynote-048","keynote-412","keynote-689","nivopostop"],"people":[],"bottlenecks":["b-dose-optimisation","b-global-access","b-drug-pricing"],"keyPapers":["paper-keynote-048-lancet-2019","paper-jean-pascal-machiels-lancet-2019","paper-pembrolizumab-head-and-neck-j-clin-oncol-2017"],"journals":[],"dependsOn":[],"notes":[],"hypothesis":"In at least two common indications, a checkpoint inhibitor dose of 10% to 25% of the labelled dose will be non-inferior for overall survival at two years, at less than a quarter of the drug cost.","rationale":"Receptor occupancy data from the original phase 1 trials showed saturation at low doses; Project Optimus now requires sponsors to justify doses, but only for new drugs.","test":"Publicly or philanthropically funded randomised non-inferiority trials in India, Brazil and Africa, with pharmacokinetic sub-studies and survival as the endpoint.","maturity":"early-clinical","actor":"research","cost":"medium","horizonYears":4},"route":"/ideas/idea-cost-low-dose-immunotherapy-trials/","neighbours":{"cancer":[{"id":"head-and-neck","kind":"cancer","name":"Head and neck squamous cell carcinoma","route":"/cancers/head-and-neck/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"drug":[{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"institution":[{"id":"tata-memorial","kind":"institution","name":"Tata Memorial Centre","route":"/institutions/tata-memorial/"}],"term":[{"id":"project-optimus","kind":"term","name":"Project Optimus","route":"/terms/project-optimus/"}],"trial":[{"id":"checkmate-141","kind":"trial","name":"CheckMate 141","route":"/trials/checkmate-141/"},{"id":"keynote-048","kind":"trial","name":"KEYNOTE-048","route":"/trials/keynote-048/"},{"id":"keynote-412","kind":"trial","name":"KEYNOTE-412","route":"/trials/keynote-412/"},{"id":"keynote-689","kind":"trial","name":"KEYNOTE-689","route":"/trials/keynote-689/"},{"id":"nivopostop","kind":"trial","name":"NIVOPOSTOP (GORTEC 2018-01)","route":"/trials/nivopostop/"}],"bottleneck":[{"id":"b-global-access","kind":"bottleneck","name":"Most of the world has almost no cancer care","route":"/bottlenecks/b-global-access/"},{"id":"b-drug-pricing","kind":"bottleneck","name":"Prices and value","route":"/bottlenecks/b-drug-pricing/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"paper":[{"id":"paper-keynote-048-lancet-2019","kind":"paper","name":"KEYNOTE-048: pembrolizumab, alone or with chemotherapy, as first treatment for recurrent or metastatic head and neck cancer","route":"/key-papers/paper-keynote-048-lancet-2019/"},{"id":"paper-pembrolizumab-head-and-neck-j-clin-oncol-2017","kind":"paper","name":"Pembrolizumab for Platinum- and Cetuximab-Refractory Head and Neck Cancer: Results From a Single-Arm, Phase II Study","route":"/key-papers/paper-pembrolizumab-head-and-neck-j-clin-oncol-2017/"},{"id":"paper-jean-pascal-machiels-lancet-2019","kind":"paper","name":"Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study","route":"/key-papers/paper-jean-pascal-machiels-lancet-2019/"}]}}