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Last updated: June 21, 2026
TROP2 (Trophoblast cell-surface antigen 2; gene TACSTD2) is a transmembrane glycoprotein originally identified on trophoblast cells. In adult tissues, TROP2 is expressed at low levels on normal epithelium but is highly overexpressed on most epithelial carcinomas — approximately 80-90% of breast, lung, urothelial, cervical, endometrial, ovarian, gastric, and pancreatic adenocarcinomas. This wide expression makes TROP2 a particularly attractive ADC target across multiple cancer types.
A TROP2 antibody-drug conjugate (ADC) is a three-part molecule:
After the ADC binds TROP2, the antibody-target complex is internalized into the cancer cell. The linker is cleaved (intracellularly or in the tumor microenvironment), and the cytotoxic payload is released to inhibit topoisomerase I, induce DNA damage, and kill the cancer cell. Membrane-permeable payloads can also diffuse to neighboring cells, producing a bystander effect that kills adjacent TROP2-low or TROP2-negative tumor cells — a key reason TROP2 ADCs work even in heterogeneous tumors without a strict TROP2 expression cutoff.
| Drug | Sponsor | Payload | Regulatory Status | Lead Indications |
|---|---|---|---|---|
| Sacituzumab govitecan (Trodelvy, IMMU-132) | Gilead | SN-38 (topo I) | FDA Apr 2020: mTNBC. FDA Apr 2021: metastatic urothelial cancer (withdrawn 2024; verify labeling). FDA Feb 2023: HR+/HER2- metastatic breast (TROPiCS-02). | Breast (TNBC + HR+/HER2-), urothelial |
| Datopotamab deruxtecan (Dato-DXd, Datroway, DS-1062) | AstraZeneca / Daiichi Sankyo | DXd (exatecan derivative, topo I) | FDA Jan 2025: HR+/HER2- metastatic breast cancer after endocrine + chemo (TROPION-Breast01). | Breast (HR+/HER2- + HER2-zero), NSCLC (non-squamous + EGFR-mut) |
| Sacituzumab tirumotecan (Sac-TMT, MK-2870, SKB264) | Merck / Kelun-Biotech | KL610023 (belotecan-derivative, topo I) | Investigational. 17 Phase 3 trials — single largest TROP2 ADC Phase 3 program. OptiTROP-Breast01 met primary endpoint in 2L+ mTNBC (2024). | Breast (TNBC + HR+/HER2-), NSCLC (sq + non-sq + maint), cervical, endometrial, ovarian, urothelial |
| Izalontamab brengitecan (SKB500, BMS-986507) | Klus Pharma (BMS partnership) | Topo I payload | Investigational. Phase 2/3: 1L TNBC (NCT06926868), post-IO urothelial (NCT07106762), post-EGFR-TKI NSCLC (NCT07100080 IZABRIGHT). | Breast (1L TNBC), urothelial (post-IO), NSCLC (EGFR-mut post-TKI) |
| YL202 | MediLink Therapeutics | Topo I payload | Investigational. Pivotal Phase 3: NCT07416994 (vs docetaxel in EGFR-mut NSCLC), NCT07461454 (vs TPC in HR+/HER2- breast). | NSCLC (EGFR-mut), Breast (HR+/HER2-) |
The first TROP2-directed ADC to receive FDA approval. Trodelvy uses the hRS7 humanized anti-TROP2 IgG1 antibody, a hydrolyzable CL2A linker, and SN-38 (the active metabolite of irinotecan) as the topoisomerase I inhibitor payload, with a drug-to-antibody ratio (DAR) of ~7.6. Approvals: FDA April 2020 for metastatic triple-negative breast cancer (ASCENT pivotal trial); FDA April 2021 for locally advanced/metastatic urothelial cancer after platinum + PD-1/PD-L1 (this urothelial indication was voluntarily withdrawn by Gilead in 2024 following the TROPiCS-04 confirmatory result — verify current labeling); FDA February 2023 for HR+/HER2- metastatic breast cancer after endocrine therapy and ≥2 prior chemotherapies in the metastatic setting (TROPiCS-02). Current Phase 3 program: NCT05633654 (sacituzumab govitecan + pembrolizumab vs physician's choice in TNBC residual disease post-neoadjuvant), NCT06524544 (sacituzumab govitecan + pembrolizumab vs SoC in advanced urothelial), NCT06081244 (ADAPT-TN-III, neoadjuvant SG vs SG + pembrolizumab in low-risk early TNBC).
AstraZeneca and Daiichi Sankyo's TROP2 ADC, using the same DXd deruxtecan exatecan-derivative payload as trastuzumab deruxtecan (Enhertu) and patritumab deruxtecan but coupled to a humanized anti-TROP2 IgG1 antibody. DAR ~4. FDA approval January 2025 for unresectable or metastatic HR+/HER2- breast cancer after endocrine therapy and chemotherapy, based on TROPION-Breast01 vs investigator's choice chemotherapy. Current Phase 3 program: NCT07291037 (Dato-DXd vs docetaxel in previously-treated TROP2-positive non-squamous NSCLC without actionable genomic alterations — TROP2-stratified by QCS digital pathology score), NCT06357533 (1L Dato-DXd + rilvegostomig PD-1/TIGIT bispecific in PD-L1-high non-squamous NSCLC), NCT07205822 (Dato-DXd in inoperable or metastatic HR+/HER2 IHC 0 'HER2-zero' breast cancer), NCT06103864 (Dato-DXd ± durvalumab vs investigator's choice chemo + pembrolizumab in 1L mTNBC). Datroway is the second FDA-approved TROP2 ADC and the first with the DXd payload.
Kelun-Biotech (Sichuan, China) developed SKB264 and licensed it to Merck in May 2022 for ex-China rights in one of the largest ADC deals in oncology history. Sac-TMT uses a humanized anti-TROP2 IgG1 antibody, a novel sulfonyl pyrimidine-CL2A cleavable linker, and KL610023 (a belotecan-derivative camptothecin analog) as the topoisomerase I payload at DAR ~7.4. Sac-TMT is now the largest single TROP2 ADC Phase 3 program in development with 17 Phase 3 trials in the ClinTrialFinder corpus, spanning: breast cancer — NCT06966700 (Sac-TMT in breast cancer, MK-2870-032), NCT06841354 (Sac-TMT monotherapy + Sac-TMT + pembro in TNBC), NCT06312176 (Sac-TMT ± pembro vs TPC in HR+/HER2- breast), NCT06393374 (MK-2870-012, Sac-TMT + pembro vs TPC in TNBC non-pCR adjuvant), NCT07628504 (Sac-TMT sequential capecitabine vs capecitabine in early-stage high-risk TNBC without BRCA mutations); NSCLC — NCT06170788 (Sac-TMT + pembro vs pembro alone in 1L PD-L1-positive metastatic NSCLC), NCT06422143 (MK-2870-023, pembro ± maintenance Sac-TMT in squamous NSCLC), NCT06824467 (Sac-TMT maintenance vs SoC in platinum-sensitive setting); cervical — NCT07216703 (MK-2870-022, Sac-TMT + pembro as 1L maintenance for cervical cancer); endometrial — NCT06952504 (Sac-TMT + pembro vs pembro alone after MSI-high progression on pembro); ovarian — NCT07318558 (MK-2870-021, Sac-TMT in non-HRD-positive advanced ovarian cancer); urothelial — NCT07419295 (MK-2870-031, Sac-TMT in urothelial). OptiTROP-Breast01 met its primary endpoint in 2L+ mTNBC (2024). Sac-TMT is not yet FDA-approved as of June 2026.
Klus Pharma's second-generation TROP2 ADC, licensed to Bristol Myers Squibb. SKB500 / BMS-986507 carries a topoisomerase I payload with linker chemistry optimized for plasma stability. Three pivotal Phase 2/3 trials are recruiting: NCT06926868 (izalontamab brengitecan vs chemotherapy in previously-untreated locally advanced, recurrent inoperable, or metastatic 1L TNBC); NCT07106762 (Phase 2/3 izalontamab brengitecan vs platinum-based chemotherapy for metastatic urothelial cancer with progression on or after immunotherapy); NCT07100080 (IZABRIGHT, izalontamab brengitecan vs platinum-pemetrexed for EGFR-mutated NSCLC after failure of EGFR TKI therapy). Izalontamab brengitecan therefore tests TROP2 ADC efficacy in three distinct post-standard-of-care settings: chemo-naive TNBC, post-IO urothelial, and post-EGFR-TKI NSCLC.
MediLink Therapeutics's TROP2 ADC, in pivotal Phase 3 development in two settings: NCT07416994 (YL202 vs docetaxel in locally advanced or metastatic EGFR-sensitive mutation non-squamous NSCLC — head-to-head against the standard 2L+ chemotherapy after EGFR TKI failure) and NCT07461454 (YL202 vs treatment of physician's choice in HR+/HER2- breast cancer). YL202 enters a competitive HR+/HER2- breast space (vs Datroway FDA-approved and vs Trodelvy FDA-approved in the same setting) but is differentiated by linker chemistry and payload exposure profile per MediLink's preclinical disclosures.
The 226 recruiting (and 79 not-yet-recruiting) TROP2 ADC trials are grouped by primary cancer type below. Most trials do NOT require TROP2 IHC testing for eligibility — the FDA-approved Trodelvy + Datroway labels do not include a TROP2 expression cutoff — but a small but growing subset of biomarker-stratified trials does require TROP2-positive status (e.g., NCT07291037 Dato-DXd in NSCLC).
Breast cancer is the densest TROP2 ADC setting, with both FDA approvals (Trodelvy + Datroway) and the largest investigational Phase 3 cluster (Sac-TMT, izalontamab brengitecan, YL202). Subdivided by HR/HER2 status.
Triple-negative breast cancer (TNBC):
HR+/HER2- breast cancer:
Broad / HER2-low / mixed-cohort breast cancer:
NSCLC is the second-largest TROP2 ADC setting. Datopotamab deruxtecan + Sac-TMT lead in non-squamous and squamous subsets, izalontamab brengitecan + YL202 lead in EGFR-mutant post-TKI.
After the voluntary 2024 withdrawal of the Trodelvy urothelial indication, the urothelial TROP2 ADC space is now an active investigational setting — Sac-TMT, Trodelvy combinations, and izalontamab brengitecan all in pivotal trials in post-EV or post-immunotherapy populations.
Ovarian cancer enters the TROP2 ADC class through the non-HRD-positive subset — where PARP inhibitors are less effective and the unmet need is highest.
Showing curated Phase 3 highlights from 226 RECRUITING + 79 not-yet-recruiting TROP2 ADC interventional trials in the ClinTrialFinder corpus as of June 21, 2026 (58 Phase 3 across the class). For the latest searches: sacituzumab govitecan, datopotamab deruxtecan, sacituzumab tirumotecan, MK-2870, TROP2 ADC.
The FDA-approved TROP2 ADC labels (Trodelvy + Datroway) do NOT require companion-diagnostic TROP2 IHC testing for eligibility — unlike HER2 ADCs (which require HER2 IHC/ISH) or CLDN18.2 ADCs (which require CLDN18.2 IHC). This is because:
However, this is an evolving area. A growing minority of investigational Phase 3 trials are biomarker-stratified or biomarker-restricted:
As more TROP2 ADCs reach the market, TROP2-IHC-restricted labels may emerge — particularly in lung cancer where heterogeneous expression is more clinically relevant. For now, most trials do not require TROP2 testing upfront, but always check each trial's specific eligibility criteria.
What is a TROP2 ADC and how does it work?
TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein expressed at high levels on ~80-90% of epithelial cancers (breast, lung, urothelial, cervical, endometrial, ovarian) with much lower expression on normal tissue. A TROP2 ADC consists of an anti-TROP2 monoclonal antibody, a chemical linker, and a topoisomerase I inhibitor payload (SN-38 in Trodelvy, DXd in Datroway, KL610023 in Sac-TMT). After binding TROP2 and being internalized, the linker releases the payload to kill the cancer cell. A "bystander effect" can also kill neighboring TROP2-low cells.
Which TROP2 ADCs are FDA-approved?
Sacituzumab govitecan (Trodelvy, Gilead): FDA Apr 2020 for mTNBC; Apr 2021 for metastatic urothelial cancer (voluntarily withdrawn by Gilead 2024 — verify labeling); Feb 2023 for HR+/HER2- metastatic breast (TROPiCS-02). Datopotamab deruxtecan (Datroway, AstraZeneca/Daiichi): FDA Jan 2025 for HR+/HER2- metastatic breast cancer (TROPION-Breast01). All other TROP2 ADCs — Sac-TMT (MK-2870), izalontamab brengitecan, YL202 — are investigational. Consult current FDA prescribing information.
Do I need TROP2 IHC testing to be eligible for a trial?
Unlike HER2 ADCs or CLDN18.2 ADCs, the FDA-approved TROP2 ADC labels do NOT currently require TROP2 IHC testing. Both Trodelvy and Datroway are approved based on cancer type, not TROP2 expression cutoff. However, biomarker-stratified trials are increasing: NCT07291037 (Dato-DXd in NSCLC) restricts enrollment to TROP2-positive tumors using the QCS digital pathology score. Always check each trial's specific eligibility criteria.
How is Sac-TMT (MK-2870) different from sacituzumab govitecan (Trodelvy)?
Both are TROP2 ADCs with topoisomerase I payloads, but they differ in: (1) antibody backbone — Trodelvy uses hRS7, Sac-TMT a different humanized anti-TROP2 antibody; (2) payload — Trodelvy delivers SN-38 (irinotecan metabolite), Sac-TMT delivers KL610023 (belotecan-derivative); (3) linker — Sac-TMT uses a novel sulfonyl pyrimidine-CL2A linker for improved plasma stability. Merck licensed Sac-TMT from Kelun-Biotech in 2022; Sac-TMT now has 17 Phase 3 trials — the largest single TROP2 ADC Phase 3 program. Sac-TMT is not yet FDA-approved as of June 2026.
What's the relationship between TROP2 ADCs and HER2 ADCs in breast cancer?
TROP2 ADCs and HER2 ADCs are complementary, not competing. HER2 ADCs (trastuzumab deruxtecan/Enhertu, trastuzumab emtansine/Kadcyla, disitamab vedotin) require HER2 expression — Enhertu approved for HER2-positive and HER2-low (DESTINY-Breast04). TROP2 ADCs (Trodelvy + Datroway) are approved without TROP2 IHC stratification. Datroway's TROPION-Breast01 trial enrolled HR+/HER2- patients regardless of HER2-low status, including HER2 IHC 0 ("HER2-zero") tumors who would not qualify for Enhertu. Clinical positioning: HER2-positive → Enhertu; HER2-low → Enhertu (after CDK4/6+ET in HR+); HER2-zero HR+ → Datroway or Trodelvy; TNBC → Trodelvy. See /mechanisms/her2-adcs.
Are TROP2 ADCs being studied in cancers outside breast and lung?
Yes — Sac-TMT (MK-2870) has Phase 3 trials in cervical (NCT07216703 1L maintenance), endometrial (NCT06952504 post-pembro), non-HRD ovarian (NCT07318558 MK-2870-021), and urothelial (NCT07419295 MK-2870-031). Trodelvy has a Phase 3 in urothelial + pembrolizumab (NCT06524544). Izalontamab brengitecan in post-IO urothelial (NCT07106762). Cross-cancer scope is comparable to HER2 ADCs and PD-1/PD-L1 inhibitors. See /trials/breast-cancer, /trials/lung-cancer-nsclc, /trials/bladder-cancer, /trials/cervical-cancer, /trials/endometrial-cancer, /trials/ovarian-cancer.
Find Matching TROP2 ADC Trials
Use ClinTrialFinder's AI-powered matching to find sacituzumab govitecan (Trodelvy), datopotamab deruxtecan (Datroway), sacituzumab tirumotecan (Sac-TMT, MK-2870), izalontamab brengitecan, and YL202 trials based on your cancer type, HR/HER2 status, prior therapy, EGFR mutation status, and country.
Find Matching TROP2 ADC TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your medical oncologist. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. FDA approval dates and indications are summarized for context only; consult the current FDA prescribing information for each drug for authoritative regulatory status.