Table 5.
Ongoing clinical trials testing immunotherapies alone or in combination in endometrial cancer. DC, dendritic cells; EC, endometrial cancer; FGFR, fibroblast growth factor receptor; FRα, folate receptor α; HER2, Human Epidermal Receptor-2; IDO1, Indoleamine 2,3-dioxygenase; MDSC, myeloid-derived suppressor cells; ORR, overall response rate; OS, overall survival; PARPi, Poly(ADP-ribose) polymerase inhibitor; PFS, progression-free survival; TAM, tumor-associated macrophages.
| Clinical Trial | Phase | Condition or Disease | Number of Patients | Drugs Combination | Mechanism of Action | Primary Endpoint (Time Frame) | Status |
|---|---|---|---|---|---|---|---|
| First-line treatment | |||||||
| DOMENICA (NCT05201547) [74] | III | dMMR (IIIC2/IV or first recurrent EC without curative treatment by RT, CT or surgery) | 142 | Dostarlimab vs. Chemotherapy | Anti-PD-1 (dostarlimab) | PFS (5 years) | Recruiting |
| AtTEND (NCT03603184) [75] |
III | EC with residual disease after surgery or inoperable FIGO III–IV | 550 | Atezolizumab or placebo + taxane platinum-based CT | Anti-PD-L1 (atezolizumab) | OS and PFS (2 years) | Active, not recruiting |
| RUBY (NCT03981796) [76] |
III | FIGO III-IV or first recurrent EC | 785 | Dostarlimab (or placebo) + taxane platinum-based CT followed by dostarlimab or niraparib (or placebo) | Anti-PD-1 (dostarlimab) and PARPi (niraparib) | Investigator assessed PFS and OS (6 years) |
Active, not recruiting |
| EnGOT-en9 (NCT03884101) [77] | III | First-line treatment of FIGO stage III, IVA, IVB or recurrent EC | 875 | Pembrolizumab+ lenvatinib vs. taxane platinum-based CT |
Anti-PD-1 (pembrolizumab) and protein kinase inhibitor (lenvatinib) | PFS (31 months) and OS (45 months) | Active, not recruiting |
| Advanced and recurrent EC | |||||||
| NRG-GY018 (NCT03914612) [78] |
III | FIGO stage III, IVA, IVB or recurrent EC | 810 | Pembrolizumab or placebo + taxane platinum-based CT | Anti-PD-1 (pembrolizumab) | PFS (5 years) | Active, not recruiting |
| GYNET (NCT04652076) [79] | I/II | Pretreated advanced EC | 240 | Netrin-1 mAbs (NP137) + Carboplatin Plus Paclitaxel and/or Pembrolizumab | Anti-PD-1 (pembrolizumab) and anti-netrin-1 (NP137) | Dose limiting toxicity occurrence, ORR (12 weeks up to 2 years) |
Recruiting |
| NCT04885413 [80] | II | Recurrent/advanced EC | 37 | Niraparib + sintilimab | PARPi (niraparib) and anti-PD-1 (sintilimab) | ORR (6 months) | Recruiting |
| NCT02912572 [81] | II | Recurrent or persistent EC MSI-H and/or POLEmut, MSS | 105 | Avelumab or Avelumab and Talazoparib or Avelumab and Axitinib | Anti-PD-L1 (avelumab) and anti-HER2 (talazoparib) and tyrosine kinase inhibitor (axitinib) | Activity of avelumab + talazoparib in EC, activity of avelumab + axitinib in MSS patients assessed by frequency of patients with PFS > 6 months or with objective tumor response (2 years) | Recruiting |
| NCT05036681 [82] | II | Metastatic EC not amenable to surgery or RT MSS | 30 | Futibatinib and Pembrolizumab | FGFR1-4 (futibatinib) and anti-PD-1 (pembrolizumab) | ORR, safety, and tolerability (1 year) | Recruiting |
| POD1UM-204 (NCT04463771) [83] | II | Advanced or metastatic EC with CT progression | 300 | Retifanlimab +/− epacadostat or pemigatinib or anti-LAG3 and anti-TIM3 | Anti-PD-1 (Retifanlimab) and anti-IDO1 (epacadostat) | ORR, PFS (2.5 years) | Recruiting |
| NCT05156268 [84] | II | Persistent/recurrent EC (including CS) | 25 | Pembrolizumab + olaparib | Anti-PD-1 (pembrolizumab) and PARPi (olaparib) | ORR (24 weeks) | Recruiting |
| NCT03526432 [85] | II | Pretreated advanced, recurrent, or persistent EC | 55 | Atezolizumab + bevacizumab | Anti-PD-L1 (atezolizumab) and anti-angiogenic (bevacizumab) | ORR (3 years) | Active, not recruiting |
| NCT03016338 [86] | II | Pretreated advanced/recurrent EC | 51 | Dostarlimab + niraparib | Anti-PD-1 (dostarlimab) and PARPi (niraparib) | Clinical benefit rate (16 weeks) | Active, not recruiting |
| DOMEC (NCT03951415) [87] | II | Recurrent or persistent EC | 55 | Olaparib + Durvalumab | Anti-PD-L1 (durvalumab) and PARPi (olaparib) | PFS (6 months) | Active, not recruiting |
| DUO-E (NCT04269200) [88] | III | After first-line treatment of advanced/recurrent EC | 699 | Taxan platinum-based CT and durvalumab followed by placebo vs. durvalumab vs. durvalumab and olaparib | Anti-PD-L1 (durvalumab) and PARPi (olaparib) | PFS (4 years) | Recruiting |
| Recurrent/relapsed/advanced EC dMMR and/or MSI-H only | |||||||
| CAN-RESPOND (NCT05550558) [89] | II | Recurrent sporadic dMMR EC | 43 | Camrelizumab + anlotinib | Anti-PD-1 (camrelizumab) and multitarget tyrosine kinase inhibitor (anlotinib) | ORR (24 months) | Not yet recruiting |
| NCT05419817 [90] | II | Recurrent EC and other solid tumors dMMR post PD1 exposure | 30 | Pembrolizumab + Sitravatinib | Anti-PD-1 (pembrolizumab) and receptor tyrosine kinases inhibitor (Sitravatinib) | ORR (12 weeks) | Recruiting |
| NCT05112601 [91] | II | Recurrent dMMR | 12 | Ipilimumab + Nivolumab vs. nivolumab | Anti-CTLA-4 (ipilimumab) and anti-PD-1 (nivolumab) | PFS (5 years) | Recruiting |
| Recurrent/relapsed/advanced EC MSS only | |||||||
| IMGN853 (NCT03835819) [92] | II | Advanced or recurrent serous EC, MSS, FRαpos | 35 | Mirvetuximab Soravtansine (IMGN853) and Pembrolizumab | Anti-FRα (Mirvetuximab soravtansine) and anti-PD-1 (pembrolizumab) | ORR, PFS (6 months) | Recruiting |