{"id":"immunotherapy-roadmap","name":"Immunotherapy roadmap: Coley's toxins → checkpoint inhibitors → engineered immunity","route":"/roadmaps/immunotherapy-roadmap/","eras":[{"era":"1891-2010","title":"Prehistory","description":"The prehistory runs from Coley's toxins (1891) through BCG for bladder cancer (1976) and interferon and IL-2 (1980s-90s) to sipuleucel-T (2010). The era brings sporadic cures, high toxicity and scepticism.","status":"historic","refs":[{"id":"cytokine-therapy","kind":"technology","name":"Cytokines & engineered cytokines","route":"/technologies/cytokine-therapy/","status":"approved","tldr":"Cytokine therapy gives immune-signalling proteins as drugs. High-dose interleukin-2 was the first immunotherapy to cure some melanomas, at great toxicity."}],"trials":[],"papers":[]},{"era":"2011-2018","title":"Checkpoint revolution","description":"Ipilimumab (2011), nivolumab and pembrolizumab (2014) and atezolizumab (2016) are approved; the tumour-agnostic MSI-H approval follows (2017) and the Nobel Prize goes to Allison and Honjo (2018). Durable responses follow across >15 tumour types.","status":"historic","refs":[{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/","status":"approved","tldr":"Ipilimumab was the first checkpoint inhibitor (2011), and proved the immune system could be unleashed against cancer."},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/","status":"approved","tldr":"Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines."},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/","status":"approved","tldr":"Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination."},{"id":"checkmate-067","kind":"trial","name":"CheckMate 067","route":"/trials/checkmate-067/","status":"positive","tldr":"The trial with the longest immunotherapy follow-up: about half of patients on the combination are alive at 10 years."}],"trials":[{"id":"checkmate-067","name":"CheckMate 067","route":"/trials/checkmate-067/","outcomes":[{"endpoint":"Overall survival at 10 years","unit":"%","arms":[{"name":"Nivolumab + ipilimumab","n":314,"value":43},{"name":"Nivolumab","n":316,"value":37},{"name":"Ipilimumab","n":315,"value":19}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407417"},{"endpoint":"Median overall survival","unit":"months","arms":[{"name":"Nivolumab + ipilimumab","value":71.9},{"name":"Nivolumab","value":36.9},{"name":"Ipilimumab","value":19.9}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407417"},{"endpoint":"Melanoma-specific survival at 10 years","unit":"%","arms":[{"name":"Nivolumab + ipilimumab","value":52},{"name":"Nivolumab","value":44},{"name":"Ipilimumab","value":23}],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2407417"},{"endpoint":"Progression-free survival (co-primary)","primary":true,"unit":"months","arms":[{"name":"Nivolumab + ipilimumab","value":11.5,"note":"HR for combination vs ipilimumab"},{"name":"Nivolumab","value":6.9},{"name":"Ipilimumab","value":2.9}],"hr":0.42,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1504030"}],"setting":"Untreated advanced melanoma: nivolumab + ipilimumab vs nivolumab vs ipilimumab","enrolled":945,"enrolledBasis":"registry"}],"papers":[]},{"era":"2018-2024","title":"Earlier lines and combinations","description":"Immunotherapy moves earlier and into combinations: neoadjuvant/adjuvant IO in melanoma, NSCLC, TNBC, bladder; IO + chemo, IO + VEGF, IO + IO (LAG-3); T-cell engagers in myeloma and lymphoma; and the first solid-tumour engager (tarlatamab) and TIL (lifileucel).","status":"current","refs":[{"id":"keynote-522","kind":"trial","name":"KEYNOTE-522","route":"/trials/keynote-522/","status":"positive","tldr":"The trial that added immunotherapy to pre-surgery chemotherapy for triple-negative breast cancer and, uniquely, improved survival."},{"id":"relatlimab-nivolumab","kind":"drug","name":"Relatlimab + nivolumab","route":"/drugs/relatlimab-nivolumab/","status":"approved","tldr":"Opdualag combines relatlimab, the first drug targeting the LAG-3 immune brake, with nivolumab for melanoma."},{"id":"tarlatamab","kind":"drug","name":"Tarlatamab","route":"/drugs/tarlatamab/","status":"approved","tldr":"The first T-cell engager to improve survival in a common solid tumour, small-cell lung cancer."},{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/","status":"approved","tldr":"Lifileucel was the first approved TIL therapy: the patient's own tumour-fighting immune cells are expanded to billions and given back."}],"trials":[{"id":"keynote-522","name":"KEYNOTE-522","route":"/trials/keynote-522/","outcomes":[{"endpoint":"Pathologic complete response (ypT0/Tis ypN0)","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","n":401,"value":64.8},{"name":"Placebo + chemotherapy","n":201,"value":51.2}],"p":"0.00055","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1910549"},{"endpoint":"Event-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","n":784,"value":81.2},{"name":"Placebo + chemotherapy","n":390,"value":72.2}],"hr":0.65,"ci":[0.51,0.83],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2409932"},{"endpoint":"Overall survival at 5 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":86.6},{"name":"Placebo + chemotherapy","value":81.7}],"hr":0.66,"ci":[0.5,0.87],"p":"0.002","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2409932"},{"endpoint":"Event-free survival at 7 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":78.3},{"name":"Placebo + chemotherapy","value":69.8}],"source":"https://www.lbbc.org/news/pivotal-progress-in-tnbc-asco-2026"},{"endpoint":"Overall survival at 7 years","unit":"%","arms":[{"name":"Pembrolizumab + chemotherapy","value":85.1},{"name":"Placebo + chemotherapy","value":77.2}],"source":"https://www.lbbc.org/news/pivotal-progress-in-tnbc-asco-2026"}],"setting":"Early-stage (II-III) TNBC: pembrolizumab + chemotherapy before surgery, pembrolizumab after","enrolled":1174,"enrolledBasis":"registry"}],"papers":[]},{"era":"2024-2027","title":"Engineered immunity arrives","description":"Personalised mRNA vaccines pass phase 3 (intismeran, 2026); PD-1×VEGF bispecifics challenge pembrolizumab; ADC + IO becomes first line; oncolytic virus RP1 approved; TCR-T and solid-tumour CAR-T approvals; in vivo CAR first-in-human.","status":"emerging","refs":[{"id":"interpath-001","kind":"trial","name":"INTerpath-001 (V940-001)","route":"/trials/interpath-001/","status":"positive","tldr":"INTerpath-001 was the first positive phase 3 trial of a personalised cancer vaccine, announced 19 August 2026."},{"id":"ivonescimab","kind":"drug","name":"Ivonescimab","route":"/drugs/ivonescimab/","status":"approved","tldr":"A Chinese bispecific that beat Keytruda head-to-head on progression-free survival in lung cancer, the first drug ever to do so."},{"id":"ascent-04","kind":"trial","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/","status":"positive","tldr":"Showed that pairing an ADC with immunotherapy beats chemotherapy plus immunotherapy in first-line PD-L1-positive TNBC."},{"id":"vusolimogene-oderparepvec","kind":"drug","name":"Vusolimogene oderparepvec","route":"/drugs/vusolimogene-oderparepvec/","status":"approved","tldr":"Vusolimogene oderparepvec is an engineered herpes virus injected into melanoma tumours, approved in August 2026 with nivolumab after immunotherapy failure."},{"id":"in-vivo-car-t","kind":"technology","name":"In vivo CAR-T","route":"/technologies/in-vivo-car-t/","status":"phase-1","tldr":"Instead of engineering T cells in a factory, an injection reprograms them inside the patient's body."}],"trials":[{"id":"interpath-001","name":"INTerpath-001 (V940-001)","route":"/trials/interpath-001/","outcomes":[{"endpoint":"Recurrence-free survival","primary":true,"arms":[{"name":"Intismeran autogene + pembrolizumab","note":"Met; hazard ratio and medians not yet disclosed (topline 19 August 2026)."},{"name":"Placebo + pembrolizumab"}],"source":"https://www.merck.com/news/merck-and-moderna-announce-phase-3-interpath-001-trial-of-intismeran-autogene-plus-keytruda-met-endpoints-of-recurrence-free-survival-rfs-and-distant-metastasis-free-survival-dmfs-in-patient/"},{"endpoint":"Distant metastasis-free survival","arms":[{"name":"Intismeran autogene + pembrolizumab","note":"Met; numbers pending presentation."},{"name":"Placebo + pembrolizumab"}]}],"setting":"Adjuvant resected stage IIB-IV melanoma: intismeran autogene + pembrolizumab vs pembrolizumab","enrolled":1137,"enrolledBasis":"registry"},{"id":"ascent-04","name":"ASCENT-04 / KEYNOTE-D19","route":"/trials/ascent-04/","outcomes":[{"endpoint":"Progression-free survival (BICR)","primary":true,"unit":"months","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","n":221,"value":11.2},{"name":"Chemotherapy + pembrolizumab","n":222,"value":7.8}],"hr":0.65,"ci":[0.51,0.84],"p":"0.0009","source":"https://dailyreporter.esmo.org/esmo-congress-2025/breast-cancer/survival-improvements-observed-with-first-line-antibody-drug-conjugates-in-triple-negative-breast-cancer"},{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","value":60},{"name":"Chemotherapy + pembrolizumab","value":53}],"source":"https://doi.org/10.1056/NEJMoa2508959"},{"endpoint":"Overall survival","unit":"months","arms":[{"name":"Sacituzumab govitecan + pembrolizumab","note":"Immature; PFS2 favoured the ADC arm in the ASCO 2026 update."},{"name":"Chemotherapy + pembrolizumab"}],"source":"https://doi.org/10.1056/NEJMoa2508959"}],"setting":"First-line PD-L1+ (CPS ≥10) metastatic TNBC: sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab","enrolled":443,"enrolledBasis":"registry"}],"papers":[]},{"era":"2028+","title":"Speculative","description":"Off-the-shelf shared-neoantigen vaccines for KRAS and TP53; interception vaccines in high-risk carriers; myeloid-reprogramming drugs that make cold tumours hot; immune-PET-guided IO selection; engineered cytokines with tumour-restricted activity.","status":"speculative","refs":[{"id":"shared-antigen-vaccine","kind":"technology","name":"Off-the-shelf cancer vaccines","route":"/technologies/shared-antigen-vaccine/","status":"phase-3","tldr":"Off-the-shelf cancer vaccines target antigens shared across patients, such as mutant KRAS or HER2 peptides, so they are made in advance rather than per person. Sipuleucel-T is still the only approved therapeutic cancer vaccine in the US; tolerance to self-antigens and weak past results hold them back."},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/","status":"phase-2","tldr":"PET scans built from radiolabelled antibodies or their fragments, to see any protein an antibody can reach, including immune cells inside tumours."},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/","tldr":"'Hot' tumours are full of immune cells and respond to immunotherapy; 'cold' tumours have kept the immune system out."}],"trials":[],"papers":[]}],"watch":[]}