PDCD1 programmed cell death 1
ENSG00000188389 · protein coding · Open Targets profile
Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005, PubMed:31754127, PubMed:32184441, PubMed:37208329). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005, PubMed:26602187). Following T-cell receptor (TCR) engagement, PDCD1 associates with TCR-CD3 in the immunological synapse and directly inhibits T-cell activation (PubMed:32184441). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:32184441). {ECO:0000269|PubMed:21276005, ECO:0000269|PubMed:26602187, ECO:0000269|PubMed:31754127, ECO:0000269|PubMed:32184441, ECO:0000269|PubMed:37208329}.
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Structure with Ligand, High-Quality Ligand
- Antibody
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM
- PROTAC
- Literature, UniProt Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.4239700138568878 (upper bound 0.7191500067710876). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 400 registry trials, updated in the last three years, of the most advanced drugs against PDCD1 (retifanlimab, sintilimab, serplulimab, toripalimab, cemiplimab, dostarlimab, pembrolizumab, camrelizumab, finotonlimab, zimberelimab, balstilimab, penpulimab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alison MoskowitzMemorial Sloan Kettering Cancer Center · 4 of 4 trials Phase 2+
- Bristol-Myers SquibbBristol-Myers Squibb · 3 of 3 trials Phase 2+Ph2/Ph3NCT04613596 · Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7brief
- Haiqing LuoAffiliated Hospital of Guangdong Medical University, Department of Head and Neck Oncology, Zhanjiang, Guangdong, China · 2 of 2 trials Phase 2+
- Ralf GutzmerJohannes Wesling Klinikum Minden · 2 of 2 trials Phase 2+
- Steven A RosenbergNational Cancer Institute (NCI) · 2 of 2 trials Phase 2+
- Alex F HerreraCity of Hope Medical Center · 1 of 2 trials Phase 2+
- Lakshmi NayakDana-Farber Cancer Institute · 1 of 2 trials Phase 2+
- Adanma Anji Ayanambakkam AttanathiYale University Cancer Center LAO · 1 of 1 trials Phase 2+
- Aiping ZhouCancer Institute and Hospital, Chinese Academy of Medical Sciences · 1 of 1 trials Phase 2+
- Alexander Z WeiColumbia University · 1 of 1 trials Phase 2+
- Alexandra LEARYGINECO - Gustave Roussy · 1 of 1 trials Phase 2+
- Amanda N FaderNRG Oncology · 1 of 1 trials Phase 2+
- Andrea B ApoloAlliance for Clinical Trials in Oncology · 1 of 1 trials Phase 2+
- Andrea CercekMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Anna BrandtUniversity Hospital, Basel, Switzerland · 1 of 1 trials Phase 2+
Registry trials of retifanlimab, sintilimab, serplulimab, toripalimab, cemiplimab, dostarlimab, pembrolizumab, camrelizumab, finotonlimab, zimberelimab, balstilimab, penpulimab updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 204 of 389 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 11 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
688 trials of drugs against PDCD1 were stopped early; 1 of the 200 most recent give no reason
Terminated, withdrawn and suspended interventional trials of retifanlimab, sintilimab, serplulimab, toripalimab, cemiplimab, dostarlimab, pembrolizumab, camrelizumab, finotonlimab, zimberelimab, balstilimab, penpulimab, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 25 most recent of 688.
- terminated · 2026-11-10 · National Cancer Institute (NCI) · Pembrolizumab“Withdrawal of tazemetostat supply led to early study closure.”
- terminated · 2026-11-10 · Amgen · Pembrolizumab“Sponsor Decision”
- suspended · 2026-11-06 · Washington University School of Medicine · Pembrolizumab“protocol amendment”
- terminated · 2026-11-05 · invoX Pharma Limited · matched by the registry's drug synonyms“The study was terminated early due to a strategic business decision by the Sponsor, unrelated to safety.”
- terminated · 2026-11-03 · Columbia University · Cemiplimab“Change in standard of care treatment for muscle-invasive bladder cancer”
- terminated · 2026-11-03 · University of Alabama at Birmingham · Pembrolizumab injection“Loss of funding”
- suspended · 2026-11-03 · National Cancer Institute (NCI) · Cemiplimab“Other - Other”
- withdrawn · 2026-11-02 · CureVac · matched by the registry's drug synonyms“In accordance with 21 CFR 312.38, CureVac is herewith withdrawing IND No. 031346 for CV09070101 (referred to as CVHNLC) for the indication of squamous Non-Small-Cell Lung Cancer (sqNSCLC), following the strategic decision to not pursue the CVHNL”
- withdrawn · 2026-11-02 · Genmab · Petosemtamab + Pembrolizumab“This study-level decision was based on the evolving treatment landscape and strategic portfolio considerations and is not related to any safety concern.”
- terminated · 2026-10-30 · Tufts Medical Center · Pembrolizumab“Futility”
- withdrawn · 2026-10-30 · Peter MacCallum Cancer Centre, Australia · Pembrolizumab“Funding issues”
- terminated · 2026-10-28 · Immedica Pharma AB · Pembrolizumab“Study enrollment was halted early based on ongoing data monitoring; no efficacy analyses were performed”
- terminated · 2026-10-21 · Merck Sharp & Dohme LLC · Pembrolizumab“Business Reasons”
- suspended · 2026-10-20 · Mayo Clinic · Pembrolizumab“transition to new institution”
- suspended · 2026-10-20 · City of Hope Medical Center · Pembrolizumab“Accrual goal Met”
- suspended · 2026-10-19 · National Cancer Institute (NCI) · matched by the registry's drug synonyms“On hold pending planned interim analysis.”
- terminated · 2026-10-19 · Agenus Inc. · Balstilimab“Sponsor decision”
- terminated · 2026-10-14 · Ryan Dackor · Pembrolizumab“Study terminated after completion of planned interim analysis of 21 patients.”
- terminated · 2026-10-09 · Compass Therapeutics · Pembrolizumab (KEYTRUDA®)“The combination therapy arm of the study with pembrolizumab did not yield an efficacy signal, so enrollment into the combination therapy arm was terminated. The monotherapy arm of the study was fully enrolled and completed.”
- withdrawn · 2026-10-09 · Georgetown University · Toripalimab-tpzi“Sponsor Decision”
- withdrawn · 2026-10-08 · Dana-Farber Cancer Institute · matched by the registry's drug synonyms“study halted prematurely prior to enrollment of first participant”
- suspended · 2026-10-05 · M.D. Anderson Cancer Center · Retifanlimab“PI Request”
- terminated · 2026-09-30 · Genmab · Pembrolizumab“Genmab has decided to discontinue further clinical development of acasunlimab following strategic portfolio prioritization. The decision was not related to safety concerns.”
- terminated · 2026-09-30 · Breast Cancer Trials, Australia and New Zealand · Pembrolizumab“Stopped on the recommendation of the BCT Independent Data and Monitoring Committee”
- terminated · 2026-09-29 · Sanofi · Pembrolizumab“Early discontinuation based on strategic sponsor decision not driven by any safety concerns”
Paediatric incentives and obligations for PDCD1's drugs
For retifanlimab, sintilimab, serplulimab, toripalimab, cemiplimab, dostarlimab, pembrolizumab, camrelizumab, finotonlimab, zimberelimab, balstilimab, penpulimab: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: yes · PDCD1 is on the list. Membership alone neither requires nor waives a pediatric study.Rule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMA/PE/0000228283 (balstilimab, Treatment of all conditions included in the category of malignant neoplasms (except melanoma, SMARCB1 (INI1) tumours, hypermutated tumours, nervous system, haematopoietic and lymphoid tissue)): W: decision granting a waiver in all age groups for all conditions or indications, 28 Feb 2025; EMEA-003104-PIP02-22 (Favezelimab;pembrolizumab, Treatment of Hodgkin lymphoma): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), date not given; EMEA-002463-PIP01-18-M02 (dostarlimab, Treatment of all conditions contained in the category of malignant neoplasms (except haematopoietic and lymphoid tissue)): PM: decision on the application for modification of an agreed PIP, 17 Jul 2024; EMEA-003566-PIP01-23 (camrelizumab, Treatment of hepatocellular carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 6 May 2024; +19 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/22/2731 withdrawn 20 Feb 2025: Treatment of small cell lung cancer; EU/3/25/3163 positive 12 Sept 2025: Treatment of oesophageal cancer; EU/3/25/3167 positive 12 Sept 2025: Treatment of gastric cancer; EU/3/24/2943 positive 25 Jul 2024: Treatment of hepatocellular carcinoma; +4 moreRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Keytruda: authorised since 17 Jul 2015; Jemperli: authorised since 21 Apr 2021; Hetronifly: authorised since 3 Feb 2025; Loqtorzi: authorised since 19 Sept 2024; +3 moreRule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: yes · Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Treatment of adult and pediatric patients 12 years and older with unresectable or metastatic tumor mutational burden high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options; Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Adjuvant treatment of adult and pediatric patients 12 years and older with Stage IIB, IIC, or III melanoma following complete resection; Pembrolizumab and berahyaluronidase alfa-pmph [Keytruda Qlex], 19 Sept 2025: Treatment of adult and pediatric patients 12 years and older with unresectable or metastatic microsatellite instability high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options; +7 moreRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-11
- Registered studies open to children: yes · 138 interventional studies of retifanlimab, sintilimab, serplulimab, toripalimab, cemiplimab, dostarlimab, pembrolizumab, camrelizumab, finotonlimab, zimberelimab, balstilimab, penpulimab include patients under 18; 75 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-11
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 26 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.