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PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers. This dossier gathers the 32 products (17 approved), 1079 trials, 12 pathways and 7 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
Inhibitory receptor on activated T cells; ligands PD-L1/PD-L2. Tumour PD-L1 expression, TMB, and MSI predict response imperfectly.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Melanoma | 30-40% | Objective response to PD-1 monotherapy (proxy) | Not an expression prevalence | Wikipedia |
| Non-small-cell lung cancer | 20-45% | Response by PD-L1 stratum (proxy) | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
| Modality | Approved | Phase 3 | Phase 2 |
|---|---|---|---|
| Antibody 19 | |||
| Bispecific antibody 10 | |||
| Cell therapy 1 | - | - | |
| fusion protein 1 | - | - | |
| Vaccine or virus 1 | - | - |
| Trial | Setting | Result | Products | ||
|---|---|---|---|---|---|
| 3 | Active | A Phase 3, Randomized, Open-label, Study of Subcutaneous Nivolumab + Relatlimab Fixed-dose Combination Versus Intravenous Nivolumab + Relatlimab Fixed-dose Combination in Participants With Previously Untreated Metastatic or Unresectable Melanoma | - | ||
| 3 | Active | A Phase 3, Open-label, Randomized, Noninferiority Trial of Subcutaneous Formulation of Nivolumab Versus Intravenous Nivolumab in Participants With Advanced or Metastatic Clear Cell Renal Cell Carcinoma Who Have Received Prior Systemic Therapy | - | ||
| 3 | Active | A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare the Efficacy and Safety of Neoadjuvant Treatment With Tislelizumab (BGB-A317, Anti-PD-1 Antibody) or Placebo Plus Platinum-Based Doublet Chemotherapy Followed By Adjuvant Tislelizumab or Placebo in Resectable Stage II or IIIA Non-Small Cell Lung Cancer | At the final analysis (median follow-up 38.5 months) overall survival favoured perioperative tislelizumab (hazard ratio 0.65, 95 percent confidence interval 0.45 to 0.93, p=0.009); 36-month overall survival 79.3 against 69.3 percent. | ||
| 3 | Negative | Untreated unresectable or metastatic melanoma: fianlimab + cemiplimab (two dose levels) vs pembrolizumab | Primary PFS endpoint not met; numerical +5.1 months median PFS at the high dose. | ||
HARMONi-3 NCT05899608 | 3 | Mixed | First-line metastatic squamous and non-squamous NSCLC, global: ivonescimab + chemotherapy vs pembrolizumab + chemotherapy | Interim PFS not statistically significant (May 2026); final readouts pending. | |
HERIZON-GEA-01 NCT05152147 | 3 | Positive | First-line HER2-positive advanced gastro-oesophageal adenocarcinoma: zanidatamab + chemotherapy ± tislelizumab vs trastuzumab + chemotherapy | PFS 12.4 vs 8.1 months (HR 0.63-0.65); OS significantly improved. | |
INTerpath-001 (V940-001) NCT05933577 | 3 | Positive | Adjuvant resected stage IIB-IV melanoma: intismeran autogene + pembrolizumab vs pembrolizumab | RFS and DMFS significantly improved (HRs pending presentation). | |
LITESPARK-012 NCT04736706 | 3 | Negative | Untreated advanced clear-cell RCC: pembrolizumab + lenvatinib ± belzutifan (or ± quavonlimab) | Primary endpoint not met (ASCO GU 2026). | |
LITESPARK-022 NCT05239728 | 3 | Positive | Clear-cell RCC at high risk after nephrectomy: adjuvant pembrolizumab + belzutifan vs pembrolizumab + placebo | DFS significantly improved vs pembrolizumab (interim; HR presented ASCO GU 2026). | |
| 3 | Active | A Randomized, Double-blind, Phase 3 Comparison of Platinum-based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-based Therapy as First-line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer | - | ||
| 3 | Active | A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer | - | ||
| 3 | Active | A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatment of Participants With Metastatic Non-small Cell Lung Cancer | - | ||
ASCENT-04 / KEYNOTE-D19 NCT05382286 | 3 | Positive | First-line PD-L1+ (CPS ≥10) metastatic TNBC: sacituzumab govitecan + pembrolizumab vs chemotherapy + pembrolizumab | PFS HR 0.65; PFS2 improved. | |
| 3 | Positive | Local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk of recurrence through nodal features (extracapsular extension with a node of 20 mm or more, or at least three involved nodes) or non-nodal features (in-transit metastases, a T4 lesion with bone invasion, perineural invasion, or a locally recurrent tumour with at least one other risk feature): cemiplimab against placebo for up to 48 weeks, with disease-free survival as the primary endpoint | Disease-free survival at 24 months 87.1 per cent with adjuvant cemiplimab against 64.1 per cent with placebo (hazard ratio 0.32, 95 per cent confidence interval 0.20 to 0.51, p<0.001), with grade 3 or higher adverse events in 23.9 against 14.2 per cent. | ||
EV-303 / KEYNOTE-905 NCT03924895 | 3 | Positive | Cisplatin-ineligible MIBC: perioperative enfortumab vedotin + pembrolizumab with cystectomy vs cystectomy alone | EFS HR 0.40; OS HR 0.50; pCR 57.1% vs 8.6%. | |
EV-304 / KEYNOTE-B15 NCT04700124 | 3 | Positive | Cisplatin-eligible MIBC: perioperative enfortumab vedotin + pembrolizumab vs neoadjuvant gemcitabine-cisplatin, both with cystectomy | EFS, OS, and pCR significantly improved (topline; details pending). | |
KEYNOTE-641 NCT03834493 | 3 | Negative | Chemotherapy-naive metastatic castration-resistant prostate cancer, prior abiraterone permitted and prior docetaxel allowed only in the hormone-sensitive setting: pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles with enzalutamide 160 mg daily, with dual primary endpoints of overall survival and radiographic progression-free survival | Median overall survival 24.7 against 27.3 months (hazard ratio 1.04, 95 percent confidence interval 0.88 to 1.22) and radiographic progression-free survival 10.4 against 9.0 months (0.98, 0.84 to 1.14); stopped for futility. Grade 3 or higher treatment-related adverse events 31.2 against 10.8 percent. | |
KEYNOTE-689 NCT03765918 | 3 | Positive | Resectable stage III-IVA HNSCC: neoadjuvant pembrolizumab, surgery, then adjuvant pembrolizumab with (chemo)radiation vs surgery and (chemo)radiation | Median EFS 59.7 vs 29.6 months (CPS ≥1). | |
KEYNOTE-921 NCT03834506 | 3 | Negative | Metastatic castration-resistant prostate cancer progressing after androgen deprivation and one androgen receptor pathway inhibitor: pembrolizumab or placebo with docetaxel and concomitant prednisone, with dual primary endpoints of radiographic progression-free survival by blinded independent central review and overall survival | Median radiographic progression-free survival 8.6 against 8.3 months (hazard ratio 0.85, 95 percent confidence interval 0.71 to 1.01) and overall survival 19.6 against 19.0 months (0.92, 0.78 to 1.09); neither endpoint met. | |
KEYNOTE-991 NCT04191096 | 3 | Negative | Metastatic hormone-sensitive prostate cancer not previously treated with a next-generation hormonal agent: pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles with enzalutamide 160 mg daily and continuous androgen deprivation, with primary endpoints of radiographic progression-free survival and overall survival | Radiographic progression-free survival hazard ratio 1.20 (95 percent confidence interval 0.96 to 1.49, p=0.9467), medians not reached; stopped for futility. Grade 3 or higher adverse events 61.9 against 38.1 percent and rash 25.1 against 9.3 percent. | |
KEYNOTE-B96 / ENGOT-ov65 NCT05116189 | 3 | Positive | Platinum-resistant recurrent ovarian cancer, 1-2 prior lines: pembrolizumab + weekly paclitaxel ± bevacizumab vs placebo + paclitaxel ± bevacizumab | OS 18.2 vs 14.0 months in CPS ≥1 (HR 0.76); ITT OS HR 0.82. | |
NIVOPOSTOP (GORTEC 2018-01) NCT03576417 | 3 | Positive | Resected locally advanced head and neck squamous cell carcinoma at high risk of relapse (extranodal extension or positive margins): nivolumab before and during postoperative cisplatin chemoradiation, then nivolumab alone, versus chemoradiation alone | Three-year disease-free survival 63.1% vs 52.5% (hazard ratio 0.76). | |
| 3 | Active | A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYVIBE-008) | - | ||
POD1UM-303/InterAACT-2 NCT04472429 | 3 | Positive | Untreated inoperable locally recurrent or metastatic squamous cell carcinoma of the anal canal: carboplatin and paclitaxel with the PD-1 antibody retifanlimab or placebo (double-blind), with progression-free survival as the primary endpoint | Median progression-free survival 9.3 months with retifanlimab plus carboplatin-paclitaxel against 7.4 months with placebo (hazard ratio 0.63, one-sided p 0.0006); approved in the United States in May 2025. | |
RELATIVITY-098 NCT05002569 | 3 | Negative | Resected stage III/IV melanoma: adjuvant nivolumab + relatlimab vs nivolumab | RFS not improved. | |
| 3 | Active | A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer | - | ||
| 3 | Active | A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Resection and Adjuvant Treatment With Nivolumab or Placebo for Participants With Resectable Stage II-IIIB Non-small Cell Lung Cancer | Eighteen-month event-free survival 70.2 percent with perioperative nivolumab against 50.0 percent with chemotherapy alone (hazard ratio 0.58, 97.36 percent confidence interval 0.42 to 0.81). | ||
CheckMate 8HW NCT04008030 | 3 | Positive | MSI-H/dMMR metastatic colorectal cancer, all lines: nivolumab + ipilimumab vs nivolumab vs chemotherapy | First-line PFS 54.1 vs 5.9 months (HR 0.21); combination vs nivolumab PFS HR 0.62. | |
CheckMate 9DW NCT04039607 | 3 | Positive | First-line unresectable HCC: nivolumab + ipilimumab vs lenvatinib or sorafenib | OS 23.7 vs 20.6 months, HR 0.79; ORR 36% vs 13%. | |
COMPASSION-16 / AK104-303 NCT04982237 | 3 | Positive | Persistent, recurrent, or metastatic cervical cancer, first line (China): cadonilimab (PD-1×CTLA-4 bispecific) + platinum-paclitaxel ± bevacizumab vs placebo + chemotherapy ± bevacizumab | OS HR 0.64; PFS HR 0.62. |
Mutations in B2M or HLA class I stop tumour cells displaying antigen; JAK1/2 loss removes interferon responsiveness (and PD-L1 induction).
No pre-existing T-cell infiltrate (cold tumour) or T cells held at the margin by TGF-β and stroma.
Exhausted T cells co-express other inhibitory receptors.
MDSCs, M2 macrophages, and VEGF suppress T-cell function and dendritic-cell maturation.
Immunoediting removes the clones that carried immunogenic mutations.
Hodgkin lymphoma responds despite deficient MHC class I. Across the CheckMate 205 biopsies, class I and beta-2-microglobulin did not predict complete remission but class II did, which points at a CD4 T cell as the effector and makes class II loss the escape route.
Fusions of the master transactivator of MHC class II lower class II on the tumour cell and in the same event place the PD-1 ligands under new promoters, so one rearrangement both hides the tumour and raises the brake.
Tumours come in three immune weathers: inflamed (T cells inside, checkpoint drugs work), excluded (T cells stuck at the edge), and desert (no T cells at all). Most common cancers are excluded or desert, and turning them 'hot' is the central problem of immunotherapy.
Which nodes have drugs →Complement is a cascade of blood proteins that punches holes in things marked by antibodies and calls in inflammatory cells. Therapeutic antibodies such as rituximab use it to kill cancer cells; tumours defend themselves with shields (CD46, CD55, CD59), and the cascade's own by-products (C5a) can recruit the myeloid cells that protect the tumour.
Which nodes have drugs →Tumours recruit the body's repair cells, fibroblasts, and keep them in wound-healing mode forever. The scar tissue they lay down (desmoplasia) squeezes blood vessels shut, walls out immune cells, stiffens the tissue in a way that itself tells cancer cells to grow, and is why pancreatic cancer is so hard to treat.
Which nodes have drugs →After glucose, glutamine is the tumour's favourite food. It feeds the energy cycle, donates nitrogen for making DNA letters, and makes the antioxidant glutathione. MYC- and KRAS-driven cancers eat so much of it that they starve the T cells next door.
Which nodes have drugs →The bacteria in the gut, and even inside tumours, influence whether cancer starts and whether immunotherapy works. Transplanting stool from responders has made some non-responders respond.
Which nodes have drugs →After DNA is copied, a proofreading crew fixes the letters the polymerase got wrong. Lose it and the genome fills with thousands of small errors, especially in repetitive stretches (microsatellites). Those errors make abnormal proteins that the immune system can see, which is why immunotherapy works so well in these cancers.
Which nodes have drugs →Tumours and immune cells eat from the same plate. Cancer cells hoard glucose and glutamine, dump lactate and acid, and burn tryptophan and arginine into by-products that paralyse T cells. The tumour wins the food fight, and the immune system loses before it has fired a shot.
Which nodes have drugs →About one cancer in eight worldwide is caused by a virus. HPV, hepatitis B and C, Epstein-Barr, HTLV-1, KSHV and Merkel cell polyomavirus each hijack the same brakes cancer normally has to mutate, which is why vaccines against HPV and HBV are among the most effective anti-cancer drugs ever made.
Which nodes have drugs →How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.
Which nodes have drugs →T cells that see their target for weeks on end without winning gradually shut down: they raise a set of brakes (PD-1, LAG-3, TIM-3, TIGIT), lose their ability to kill, and eventually lock this state into their DNA. Checkpoint drugs rescue the ones that are only partly exhausted; the terminally exhausted are beyond reach.
Which nodes have drugs →Seven steps the immune system must complete to kill a tumour: release of antigens, pick-up by dendritic cells, priming of T cells in lymph nodes, travel, entry into the tumour, recognition, and killing. Every immunotherapy pushes on one step; every escape blocks one.
Which nodes have drugs →A tumour is not just cancer cells. It is a neighbourhood of fibroblasts, immune cells, blood vessels, nerves, and scaffolding that the cancer recruits and corrupts, and that decides whether drugs and immune cells can get in.
Which nodes have drugs →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| PD-L1 IHC 22C3 pharmDx Agilent (Dako) · FDA CDx 2015 | IHC | TPS at least 1% or at least 50% (NSCLC); CPS at least 1 (head and neck, oesophageal, gastric); CPS at least 10 (TNBC, gastric first line); CPS at least 1 (cervical) | |
| PD-L1 IHC 28-8 pharmDx Agilent (Dako) · FDA CDx 2020 | IHC | TC at least 1% (nivolumab plus ipilimumab, first-line NSCLC) | |
| FoundationOne CDx Foundation Medicine (Roche) · FDA CDx 2017 | NGS tissue | Per companion claim: EGFR, ALK, BRAF V600, ERBB2 amplification, KRAS wild-type, BRCA1/2 and HRR genes, PIK3CA, MET exon 14, RET, FGFR2 fusions, IDH1, NTRK fusions; MSI-high; TMB at least 10 mutations per megabase | |
| VENTANA MMR RxDx Panel Roche Diagnostics · FDA CDx 2021 | IHC | Loss of nuclear expression of any mismatch-repair protein in tumour cells (dostarlimab, endometrial cancer) | |
| MSI by PCR (Promega MSI Analysis System and equivalents) Promega and others · LDT | PCR | Instability at two or more of five markers (MSI-high); NGS panels report MSI from hundreds of loci | |
| Tumour mutational burden (FoundationOne CDx and equivalents) Foundation Medicine and others · FDA CDx 2020 | NGS tissue | At least 10 mutations per megabase (pembrolizumab, tumour-agnostic, KEYNOTE-158) |
| Cell line | Identifiers | Why it is used |
|---|---|---|
| MC38 Mus musculus | CVCL_B288 | Mouse colon; PD-1 responsive. |
| CT26 Mus musculus | CVCL_7254 | Mouse colon; partially responsive. |
| B16-F10 Mus musculus | CVCL_0159 | Mouse melanoma; PD-1 refractory unless combined. |
| 4T1 Mus musculus | CVCL_0125 | Mouse breast; refractory, metastatic. |
| LL/2 Mus musculus | CVCL_4358 | Lewis lung carcinoma; refractory. |
| EMT6 Mus musculus | CVCL_1923 | Mouse breast; responsive. |
| YUMMER1.7 Mus musculus | CVCL_A2AX | UV-mutagenised Braf/Pten melanoma; responsive. |
| KPC-derived lines | not resolved | Pancreatic; immune-excluded and refractory. |
Syngeneic lines are the only immunocompetent option for human checkpoint biology but carry far higher mutation burden than most human tumours, and the human antibodies do not bind mouse PD-1, so surrogate antibodies are used.
Why unresolved. Trials fixed two years by convention; long-term CheckMate 067 and KEYNOTE-006 data show durable remissions after stopping, and the cost and toxicity of unnecessary years are large.
What would answer it. Randomised stop-versus-continue trials with ctDNA-guided arms, powered for overall survival.
Why unresolved. Most patients have primary resistance: no T-cell infiltrate or T cells excluded by stroma. Radiation, oncolytic viruses, ADCs and vaccines each prime in some models, but no combination has produced a reliable conversion in people.
What would answer it. Randomised combination trials with mandatory on-treatment biopsies linking immune-infiltration change to survival, and mechanistic studies of exclusion drivers such as TGF-beta and CXCL12.
Why unresolved. NADINA, CheckMate 816, NICHE-2 and KEYNOTE-522 show deep pathological responses, but regulators still want event-free or overall survival and surgeons want to know who can safely have less surgery.
What would answer it. Validation of pathological complete response as a surrogate across tumour types and de-escalation trials that omit or reduce surgery in complete responders.
Query for this target: (TITLE:"PD-1" OR ABSTRACT:"PD-1" OR TITLE:"PDCD1" OR ABSTRACT:"PDCD1") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PD-1, not a curated reading list.
The dossier as machine-readable JSON, at /api/v1/dossiers/pd1.json: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/pd1.json. Licence CC BY-NC 4.0.