Table 2 Selected trials testing EMT-targeting agents or agents with indirect effects on EMT
Trial identifiersa | Agents and trial cohort | Outcomes | Adverse events | Expected completion date |
|---|---|---|---|---|
Anti-netrin 1 antibodies | ||||
NCT02977195 (phase I)181 | NP137 in patients with advanced-stage endometrial cancer (n = 14) | 1 partial response >6 months, stable disease ≥3 months in a further 6 patients | Grade ≥3 TRAEs in 21% of patients | NA |
NCT06203821 (phase I) | Perioperative NP137 plus FOLFIRINOX in patients with resectable PDAC (enrolment target of 25 patients) | – | – | December 2027 |
LIVER-NET1 NCT05546879 (phase I) | NP137 plus atezolizumab–bevacizumab as first-line therapy for patients with advanced-stage HCC (enrolment target of 52 patients) | – | – | March 2027 |
LAPNet1 NCT05546853 (phase Ib) | NP137 plus modified FOLFIRINOX in patients with locally advanced PDAC | – | – | March 2027 |
IMMUNONET NCT05605496 (phase II) | NP137 plus an anti-PD-(L)1 antibody in patients with advanced-stage solid tumours (enrolment target 87 patients) | – | – | November 2026 |
AXL inhibitors | ||||
CTR20160875 (phase Ib)272 | Ningetinib plus gefitinib in patients with EGFR-mutant NSCLC (n = 104) | ORR 20% for tumours harbouring AXL amplifications; 27.6% for those with AXL overexpression | Grade ≥3 TRAEs in 41.7% of patients | NA |
NCT02544633 (phase II)189 | Glesatinib, as orally administered capsule or tablet formulations, in patients with advanced-stage solid tumours (n = 182) | MET/AXL-altered NSCLC: ORR 25.9%, mPFS 4.1 months, mOS 9.7 months | Grade ≥3 TRAEs in 11.9% of patients; clinically serious events in 33.3–44.4% | NA |
MET/AXL-altered HNSCC: ORR 0%, mPFS 1.1 months, mOS 4.0 months | ||||
Other cancer types: ORR 10%, mPFS 2.8 months, mOS 5.8 months | ||||
NCT03599518 (phase I)273 | DS-1205c plus gefitinib in patients with EGFR-mutant advanced-stage NSCLC (n = 20) | ORR 0%, SD in 25% of patients, mPFS 6.9 months | Grade ≥3 TRAEs in 30% of patients | NA |
NCT00920192 (phase I–II)190 | Foretinib in patients with advanced-stage HCC (n = 39) | ORR 22.9%, SD 60%, mPFS 4.2 months, mOS 15.7 months | Clinically serious adverse events in 10.3% of patients | NA |
TGFβ inhibitors | ||||
Galunisertib plus gemcitabine vs gemcitabine in patients with metastatic PDAC (n = 104/52) | ORR 11% vs 2%; mPFS 4.1 vs 2.9 months; mOS 8.9 vs 7.1 months | Grade ≥3 TRAEs in 35% vs 27% of patients | NA | |
NCT02423343 (phase Ib–II)276 | Galunisertib plus nivolumab in patients with advanced-stage solid tumours (phase Ib, n = 15) or advanced-stage NSCLC (phase II, n = 25) | Phase Ib: ORR 0%, DCR 46.7% | Phase II: grade ≥3 TRAEs in 8% of patients | NA |
Phase II: ORR 24%, DCR 50%, mPFS 5.26 months, mOS 11.99 months | ||||
Snail degradation | ||||
NCT02595372 (phase II)277 | High-dose omeprazole plus ACT as neoadjuvant therapy for patients with resectable TNBC (n = 42) | pCRs in 71.8% of patients | Grade ≥3 TRAEs included neutropenia (in 19% of patients), febrile neutropenia (7%) and peripheral neuropathy (7%); no grade 3–4 events were attributed to high-dose omeprazole | NA |
NCT04930991 (phase II) | Omeprazole in pre-operative PDAC | – | – | June 2026 |
Anti-clusterin antibodies | ||||
NCT04364620 (phase II)278 | Sotevtamab plus docetaxel in patients with advanced-stage NSCLC (n = 35) | ORR 17.1%, DCR 45.7%; 1-year OS 33.9% | Most frequent adverse events included fatigue, IRRs, diarrhoea, nausea and anaemia | NA |
NCT06225843 (phase II) | Sotevtamab plus FOLFOX as neoadjuvant therapy prior to resection of liver metastases in patients with metastatic CRC (enrolment target 17 patients) | – | – | June 2026 |
EMT reversal or inhibition | ||||
NCT04664829 (phase I) | Bexarotene plus capecitabine in patients with metastatic TNBC (enrolment target 12 patients) | – | – | September 2025 |
NCT01990196 (phase II) | Trametinib or dasatinib plus neoadjuvant ADT in patients with resectable prostate cancer (enrolment target 45 patients) | – | – | September 2026 |
NCT05550415 (phase II) | Simvastatin plus neoadjuvant ACT in patients with resectable TNBC (enrolment target 26 patients) | – | – | August 2025 |
NCT03264547 (phase III)279 | Trastuzumab–petuzumab plus eribulin vs trastuzumab–pertuzumab plus doxetaxel or paclitaxel in patients with advanced-stage HER2+ breast cancer | ORR 76.8% vs 75.2%; mPFS 14.0 vs 12.9 months (HR 0.95, 95% CI 0.76–1.19); mOS NR vs 65.3 months | Grade ≥3 TRAEs in 58.9% vs 59.2% of patients | NA |
NCT05445791 (phase III) | Metformin plus EGFR TKIs in patients with advanced-stage EGFR-mutant NSCLC (target enrolment 312 patients) | – | – | July 2025 |
NCT06044025 (phase I) | Metformin plus turmeric in patients with advanced-stage CRPC (enrolment target 30 patients) | – | – | October 2027 |