CD38 CD38 molecule
ENSG00000004468 · protein coding · Open Targets profile
Multifunctional transmembrane glycoprotein able to exert enzymatic activities and also to mobilize calcium, to transduce signals, to adhere to hyaluronan and to other ligands. Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (PubMed:7961800, PubMed:8253715). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. At both pH 5.0 and pH 7.4 preferentially transforms 2'- phospho-cADPR into NAADP(+), while preferentially cleaving NADP(+) to cADPR and ADPRP rather than into NADDP(+) (PubMed:16690024). Has cADPR hydrolase activity (PubMed:7961800, PubMed:8253715). Functions also as a receptor that binds the ligand CD31 on endothelial cells, promoting lymphocyte activation, proliferation, and migration across the endothelial barrier (PubMed:9551996). Involved in the regulation of crucial dendritic cell functions acquired at the mature stage, such as CCL21-driven migration, survival, and Th1-polarizing activity (PubMed:16293598). In lamina propria T lymphocytes, CD38/CD31 cognate interactions initiate a multistep signaling pathway resulting in activation of LCK anf LAT, followed by cytokine release (PubMed:11259373). {ECO:0000269|PubMed:11259373, ECO:0000269|PubMed:16293598, ECO:0000269|PubMed:16690024, ECO:0000269|PubMed:7961800, ECO:0000269|PubMed:8253715, ECO:0000269|PubMed:9551996}.
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 Withdrawn means the drug was pulled from the market or from development.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, High-Quality Pocket
- Antibody
- Approved Drug, UniProt loc high conf, GO CC high conf, UniProt SigP or TMHMM, Human Protein Atlas loc
- PROTAC
- Database Ubiquitination, Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 0.8549100160598755 (upper bound 1.1538000106811523). 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 CD38 (isatuximab, daratumumab, felzartamab, mezagitamab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Lei ZhangThrombosis and Haemostasis Diagnosis Treatment Center · 6 of 6 trials Phase 2+
- Bristol-Myers SquibbBristol-Myers Squibb · 5 of 5 trials Phase 2+Ph3NCT03651128 · Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM)brief
- Andrew YeeMassachusetts General Hospital · 3 of 3 trials Phase 2+
- Hartmut GoldschmidtUniversity Hospital Heidelberg · 3 of 3 trials Phase 2+Ph3NCT06216158 · Iberdomide vs. Iberdomide Plus Isatuximab Maintenance Therapy Post ASCT in Newly Diagnosed Multiple Myelomabrief
- Jesús San MiguelClínica Universitaria de Navarra · 3 of 3 trials Phase 2+
- Joan BladéHospital Clinic of Barcelona · 3 of 3 trials Phase 2+
- Juan José Lahuerta PalaciosHospital Universitario 12 de Octubre · 3 of 3 trials Phase 2+
- Sikander AilawadhiSWOG Cancer Research Network · 3 of 3 trials Phase 2+
- Shaji K. KumarMayo Clinic in Rochester · 2 of 4 trials Phase 2+Ph2NCT05497804 · Combination Treatment Therapy Approaches for the Treatment of High-Risk Multiple Myeloma, REACH Trialbrief
- Binod DhakalMedical College of Wisconsin · 2 of 3 trials Phase 2+
- Carl O LandgrenUniversity of Miami · 2 of 2 trials Phase 2+
- Fernando FervenzaMayo Clinic · 2 of 2 trials Phase 2+
- Fredrik SchjesvoldOslo University Hospital · 2 of 2 trials Phase 2+
- Luciano CostaUniversity of Alabama at Birmingham · 2 of 2 trials Phase 2+
- Mª Victoria MateosHospital Clínico Universitario de Salamanca · 2 of 2 trials Phase 2+
Registry trials of isatuximab, daratumumab, felzartamab, mezagitamab 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; 236 of 372 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. 28 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
75 trials of drugs against CD38 were stopped early
Terminated, withdrawn and suspended interventional trials of isatuximab, daratumumab, felzartamab, mezagitamab, 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 75.
- withdrawn · 2026-10-22 · City of Hope Medical Center · Daratumumab“Budgetary constraints”
- terminated · 2026-09-29 · Hoffmann-La Roche · Daratumumab“The study was terminated prematurely because the Sponsor decided not to pursue the development of forimtamig.”
- withdrawn · 2026-09-11 · Fred Hutchinson Cancer Center · matched by the registry's drug synonyms“Study withdrawn before opening to accrual.”
- withdrawn · 2026-06-18 · Regeneron Pharmaceuticals · Daratumumab“Sponsor Decision”
- withdrawn · 2026-06-09 · UNC Lineberger Comprehensive Cancer Center · Daratumumab“budget”
- terminated · 2026-05-19 · Genmab · Daratumumab“The sponsor has decided to discontinue further development of GEN3014 after a comprehensive review of the data, market landscape, and strategic priorities.”
- withdrawn · 2026-05-15 · Roswell Park Cancer Institute · Daratumumab and Recombinant Human Hyaluronidase“Sponsor withdrawal of supplying investigational drug”
- withdrawn · 2026-05-13 · Institute of Hematology & Blood Diseases Hospital, China · Daratumumab Injection“No eligeble patients”
- terminated · 2026-05-13 · University Hospital, Caen · Ixazomib and Daratumumab“Early termination (regarding the follow-up of the patients). The required sample size was reached, and the primary endpoint was met.”
- terminated · 2026-04-24 · M.D. Anderson Cancer Center · Daratumumab“<75% participation”
- terminated · 2026-01-30 · Teva Branded Pharmaceutical Products R&D LLC · Daratumumab“After completion of Phase 1 Dose Escalation of this study the sponsor decided not to proceed with Phase 2a due to strategic reasons. Thus, no participants were enrolled for Phase 2a and the study was terminated early.”
- terminated · 2026-01-29 · Teva Branded Pharmaceutical Products R&D LLC · Daratumumab“Due to strategic reasons (no safety concerns).”
- terminated · 2026-01-05 · Universitätsklinikum Hamburg-Eppendorf · daratumumab/bortezomib/dexamethasone (DVD), daratumumab/lenalidomide/dexamethasone (DRD), carfilzomib/daratumumab/dexamethasone (KDD), daratumumab/pomalidomide/dexamethasone (DPD), isatuximab/carfilzomib/dexamethasone (Isa-KD)“The reason for the end of recruitment is that the recruitment target could not be achieved despite all efforts and the G-BA (financing party) does not consider a continuation of the AlloRelapseMM study to be expedient.”
- terminated · 2025-12-30 · Mayo Clinic · Daratumumab“Slow accrual”
- terminated · 2025-12-16 · Prothena Biosciences Ltd. · matched by the registry's drug synonyms“The AFFIRM-AL clinical trial did not meet its primary endpoint.”
- terminated · 2025-12-10 · University Hospital, Grenoble · Each patient will undergo in the first step of the study belatacept treatment and in the second apheresis and daratumumab“limited clinically significant reduction on global cPRA levels (access to transplantation was unchanged), as well as restrictions in belatacept supply.”
- terminated · 2025-11-04 · Incyte Corporation · Daratumumab SC“This decision follows recruitment difficulties. No safety-related concerns impacted this decision.”
- terminated · 2025-10-21 · University of California, San Diego · Daratumumab-Hyaluronidase-Fihj@1,800 Mg-30,000 Unit/15 mL@SUBCUT@VIAL (ML)“The trial met its primary endpoint.”
- withdrawn · 2025-10-01 · Georgetown University · Daratumumab and hyaluronidase-fihj“Lack of accrual”
- terminated · 2025-09-23 · Sanofi · isatuximab SAR650984“Study was stopped after interim analysis for all 4 cohorts with results either not fulfilling the pre-planned interim analysis criteria or fulfilling the criteria but as per sponsor decision. It was not due to any safety concern”
- terminated · 2025-09-17 · Sanofi · Isatuximab SAR650984“Terminated due to non-safety reasons”
- terminated · 2025-09-09 · Sanofi · Isatuximab“Study was prematurely stopped due to sponsor decision (stage 2 efficacy criteria not met); not due to safety concerns.”
- terminated · 2025-05-26 · Mayo Clinic · Daratumumab“funding - sponsor filing Chapter 11 bankruptcy”
- terminated · 2025-05-21 · Sumithira Vasu · Daratumumab“Poor acccrual”
- terminated · 2025-05-18 · Mayo Clinic · Daratumumab“Low/slow accrual - did not proceed to Phase 2”
Paediatric incentives and obligations for CD38's drugs
For isatuximab, daratumumab, felzartamab, mezagitamab: 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 · CD38 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 · EMEA-003502-PIP02-24 (mezagitamab, Treatment of primary immunoglobulin A nephropathy): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 28 Jan 2025; EMEA-002152-PIP01-17-M04 (daratumumab, Treatment of lymphoid malignancies (except mature B-cell neoplasms)): PM: decision on the application for modification of an agreed PIP, 13 Sept 2024; compliance positive 13 Dec 2024; EMEA-003502-PIP01-23 (mezagitamab, Treatment of immune thrombocytopenia): P: decision agreeing on a investigation plan, with or without partial waiver(s) and or deferral(s), 16 Aug 2024; EMEA-002205-PIP02-23 (Isatuximab, Treatment of malignant neoplasms of the haematopoietic and lymphoid tissue): W: decision granting a waiver in all age groups for all conditions or indications, 8 Mar 2024; +3 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/3/18/2020 withdrawn 25 May 2018: Treatment of AL amyloidosis; EU/3/13/1153 expired 17 Jul 2013: Treatment of plasma-cell myeloma; EU/3/25/3142 positive 20 Oct 2025: Treatment of primary IgA nephropathy; EU/3/25/3156 positive 21 Nov 2025: Treatment of primary membranous nephropathy; +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 · Darzalex: authorised since 20 May 2016; Sarclisa: authorised since 30 May 2020Rule: 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: no · FDA's table lists no pediatric approval of isatuximab, daratumumab, felzartamab, mezagitamabRule: 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 · 25 interventional studies of isatuximab, daratumumab, felzartamab, mezagitamab include patients under 18; 16 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 4 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.