Table 5

Ongoing trials investigating novel therapeutic agents for advanced, persistent, or recurrent ECS

Trial	NCT identifier	Design	Setting	Treatment arms	Primary endpoints	Status	Estimated enrollment	ECD
A phase II trial of pembrolizumab plus lenvatinib for the treatment of patients with advanced uterine and ovarian carcinosarcomas	NCT05147558	Open-label, single-center, single-arm, phase II trial	Advanced uterine and ovarian carcinosarcomas, up to three prior CHT lines	Lenvatinib (20 mg once daily OS)+pembrolizumab (200 mg every 3 weeks IV), until PD or unacceptable toxicity	ORR PFS	Recruiting	40	December 23, 2023
A phase II trial of pembrolizumab plus olaparib for the treatment of patients with peristent/recurrent endometrial cancers	NCT05156268	Open-label, single-center, single-arm, phase II trial	Persistent/recurrent endometrial cancers (serous, grade 3 endometrioid, undifferentiated, ECS)	Olaparib 300 mg PO twice daily+pembrolizumab 200 mg IV q21, until PD or unacceptable toxicity	ORR	Recruiting	25	January, 2024
An open-label, non-randomized multisite phase II trial combining bevacizumab, atezolizumab, and rucaparib for the treatment of previously treated recurrent and progressive endometrial carcinoma	NCT03694262 (Endo BARR)	Open-label, multicenter, single-arm, phase II trial	Recurrent, persistent, or progressive endometrial carcinoma, 1–2 prior CHT lines	Atezolizumab 1200 mg IV d1+bevacizumab 15 mg/kg IV d1 q21+rucaparib 600 mg orally twice daily, until PD or unacceptable toxicity	ORR	Active, not recruiting	30	June 28, 2026
Efficacy of spartalizumab across multiple cancer-types in patients with PD1-high mRNA expressing tumors defined by a single and pre-specified cut-off point	NCT04802876	Open-label, multicenter, single-arm, phase II trial	Metastatic PD1-high-expressing tumors	Spartalizumab (PDR001) 400 mg IV q28, until PD or unacceptable toxicity	ORR	Recruiting	141	December 11, 2024
Phase II trial of single-agent nivolumab in patients with microsatellite unstable/mismatch repair-deficient/hypermutated uterine cancer	NCT03241745	Open-label, single-center, single-arm, phase II trial	Microsatellite unstable/mismatch repair- deficient/hypermutated uterine cancer	Nivolumab 480 mg IV once every 4 weeks, until PD or unacceptable toxicity	PFS	Active, not recruiting	35	August, 2023
A phase II trial of IDO inhibitor, BMS-986205, and PD-1 inhibitor, nivolumab, in patients with recurrent or persistent endometrial cancer or endometrial carcinosarcomas (CA017-056)	NCT04106414	Open-label, multicenter, phase II RCT	Recurrent or persistent endometrial cancer or endometrial carcinosarcomas	· Arm 1: Nivolumab 480 mg every 4 weeks. · Arm 2: Nivolumab 480 mg every 4 weeks with BMS-986205 100 mg.	ORR	Active, not recruiting	24	September, 2023
A phase III, randomized, double-blind, multicenter study of dostarlimab (TSR-042) plus carboplatin-paclitaxel vs placebo plus carboplatin-paclitaxel in patients with recurrent or primary advanced endometrial cancer (RUBY)	NCT03981796 ENGOT-EN6 GOG-3031	Double-blind, multicenter, phase III RCT	Recurrent or primary advanced endometrial cancer	· Arm 1: Dostarlimab+carboplatin–paclitaxel followed by dostarlimab · Arm 2: Dostarlimab placebo+carboplatin–paclitaxel followed by dostarlimab placebo · Arm 3: Dostarlimab+carboplatin–paclitaxel followed by dostarlimab+niraparib · Arm 4: Dostarlimab placebo+carboplatin–paclitaxel followed by dostarlimab placebo+niraparib placebo	PFS OS	Active, not recruiting	785	December 23, 2026
A multicentric randomized phase II/III evaluating TSR-042 (anti-PD-1 mAb) in combination with niraparib (parpi) vs niraparib alone compared with chemotherapy in the treatment of metastatic or recurrent endometrial or ovarian carcinosarcoma after at least one line of chemotherapy	NCT03651206 (ROCSAN)	Open-label, multicenter, phase II/III RCT	Metastatic or recurrent endometrial or ovarian carcinosarcoma, at least one prior CHT line	· Arm 1: Niraparib 200 to 300 mg PO QD · Arm 2: Niraparib 200 to 300 mg PO QD+dostarlimab 500 mg IV q21 for the four first cycles, followed by 1000 mg IV q42 · Arm 3: ICT (standard of care)	ORR OS	Recruiting	196	June, 2025
A phase II trial of durvalumab(MEDI4736)(anti-PD-L1 antibody) with or without tremelimumab (anti-CTLA-4 antibody) in patients with persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma	NCT03015129	Open-label, multicenter, phase II RCT	Persistent or recurrent endometrial carcinoma and endometrial carcinosarcoma	· Arm 1: Durvalumab 1500 mg every 4 weeks, until PD or unacceptable toxicity · Arm 2: Durvalumab 1500 mg+remelimumab 5 mg IV every 4 weeks for up to four cycles, and then continue durvalumab alone, until PD or unacceptable toxicity	ORR	Active, not recruiting	80	January, 2024
A phase II study of the WEE1 Inhibitor AZD1775 in women with recurrent or persistent uterine serous carcinoma or uterine carcinosarcoma	NCT0366834	Open-label, multicenter, single-arm, phase II trial	Recurrent or persistent USC or ECS, at least one prior CHT line	Adavosertib 300 mg PO QD d1–5, 8 to 12 q21, until PD or unacceptable toxicity	ORR PFS6	Recruiting	80	June 1, 2023
Feasibility IB trial of paclitaxel/carboplatin+galunisertib (a small molecule inhibitor of the kinase domain of type 1 TGF-β receptor) in patients with newly diagnosed, persistent or recurrent carcinosarcoma of the uterus or ovary	NCT03206177	Open-label, multicenter, single-arm, phase IB trial	Newly diagnosed, persistent or recurrent carcinosarcoma of the uterus or ovary	Galunisertib 150 mg PO Twice daily d4−17+Paclitaxel 175 mg/mq IV d1+CBDCA AUC 5/6 IV d1 q21, until PD or unacceptable toxicity	Proportion of patients with completion of 4 cycles	Active, not recruiting	26	August 19, 2023
Phase II trial on trabectedin In the treatment of advanced uterine and ovarian carcinosarcoma	NCT02993705 (MITO26)	Open-label, multicenter, single-arm, phase II trial	Advanced or recurrent ovarian and uterine carcinosarcoma, up to two prior CHT lines	Trabectedin 1.3 mg/mq IV q21, until PD or unacceptable toxicity	ORR	Completed (no results posted)	45	November 13, 2019
A phase II study of metformin in combination with doxycycline in patients with localized breast, and uterine, and cervical cancer	NCT02874430	Open-label, multicenter, single-arm, phase II trial	Localized breast, uterine, and cervical cancer	Metformin PO QD d1–3 and twice daily d4+doxycycline PO twice daily d1 q7 for up to two courses	Change in the percent of stromal cells expressing caveolin-1 (CAV1) at an intensity of 1+ or greater assessed by immunohistochemistry	Active, not recruiting	27	June, 2022
A phase II/III study of paclitaxel/carboplatin alone or combined with either trastuzumab and hyaluronidase-oysk (HERCEPTIN HYLECTA) or pertuzumab trastuzumab and hyaluronidase-Zzfx (PHESGO) in Her2-positive, stage I–IV endometrial serous carcinoma or carcinosarcoma	NCT05256225 NCI-2022–01540 NRG-GY026	Multicenter, phase II/III RCT	Newly diagnosed, HER2 positive endometrial serous carcinoma or carcinosarcoma, no prior CHT	Arm 1 (comparator): Paclitaxel IV+CBDCA IV q21 for six cycles (± further four cycles, if SD or PR) Arm 2: Paclitaxel IV+CBDCA IV+trastuzumab SC q21 for six cycles (± further four cycles, if SD/PR) → Trastuzumab maintenance q21 for up to 1 year (or 3 years, if SD/PR) Arm 3: Paclitaxel IV+CBDCA IV+pertuzumab + Trastuzumab SC q21 for six cycles (± further four cycles, if SD/PR) → pertuzumab+trastuzumab maintenance q21 for up to 1 year (or 3 years, if SD/PR)	PFS OS DLTs	Not yet recruiting	326	October 31, 2027
Pazopanib vs pazopanib plus gemcitabine in patients with relapsed or metastatic uterine leiomyosarcomas or uterine carcinosarcomas: a multicenter, randomized phase II clinical trial of the NOGGO and AGO	NCT02203760 NOGGO U1 (PazoDoble)	Multicenter, single-arm, phase III RCT	Relapsed or metastatic carcinosarcomas, prior CHT lines	Arm 1: Pazopanib 800 mg PO QD+gemcitabine 1000 mg/mq IV d1,8q21, until PD or unacceptable toxicity Arm 2 (comparator): Pazopanib 800 mg PO QD, until PD or unacceptable toxicity	PFS6	Recruiting	20	December, 2023
A dose escalation study of HFB301001 (OX40 agonist antibody) in adult patients with advanced solid tumors	NCT05229601	Open-label, multicenter, two-stage, phase I trial	Advanced solid tumors (including ECS)	Dose escalation: participants will be administered HFB301001 dose level 1 IV in cohort 1. Participants in cohorts 2 to 4 will receive dose levels 2 to 4, respectively.	AEs DLTs RP2D	Recruiting	84	January, 2024
A phase II study of AZD0530 in recurrent or metastatic soft tissue sarcoma	NCT00659360 NCI-2009–01054	Open-label, multicenter, single-arm, phase II trial	Recurrent, locally advanced or metastatic soft tissue sarcoma	AZD0530 (saracatinib) 175 mg PO QD, until PD or unacceptable toxicity	DCR	Completed (results posted): DCR: 0% ORR: 0% OS: 16.1 months PFS: 1.7 mos	17	November, 2012 (Last update posted: June 29, 2018)
A phase II study of VEGF-Trap in recurrent or metastatic gynecologic soft tissue sarcomas	NCT00390234 NCI-2009–00177	Open-label, multicenter, single-arm, phase II trial	Locally advanced, unresectable, or metastatic gynecologic soft tissue sarcoma	Ziv-aflibercept IV q14, until PD or unacceptable toxicity	ORR PFS6	Completed (results posted): ORR: 0% PFS6: 1.6 months	63	August, 2013 (Last update posted: December 7, 2015)
Phase I study of mirvetuximab soravtansine (IMGN853) and rucaparib for recurrent endometrial, ovarian, fallopian tube or primary peritoneal cancer	NCT03552471 NCI-2018–00438	Open-label, multicenter, single-arm, phase I trial	Recurrent endometrial, ovarian, fallopian tube, or primary peritoneal cancer	Mirvetuximab soravtansine IV q21+rucaparib PO Twice daily, until PD or unacceptable toxicity	RP2D	Active, not recruiting	25	December 31, 2022
Targeted complex therapy for advanced melanoma, gynecologic cancers, and other malignancies: Nab-paclitaxel (Abraxane)/bevacizumab complex (AB-complex)	NCT02020707 NCI-2013–01782	Open-label, multicenter, single-arm, phase I trial	Unresectable stage IV melanoma or gynecological cancers	Nab-paclitaxel/bevacizumab-complex IV d1,8,15 q28, until PD or unacceptable toxicity	MTD	Recruiting	73	June 1, 2025
A phase I, open-label, multicenter study of INCB123667 as monotherapy in participants with selected advanced solid tumors	NCT05238922	Open-label, multicenter, single-arm, phase II trial	Advanced or metastatic solid tumors	Part 1 a: dose escalation to identify the RDE(s) with a starting dose of INCB123667 of 50 mg QD. Part 1B: dose expansion	Part 1A: DLTs, AEs Part 1B: PK parameters, ORR, DCR, DOR	Recruiting	155	July 30, 2026
A Phase II study evaluating the efficacy and safety of DKN-01 as a monotherapy or in combination with paclitaxel in patients with recurrent epithelial endometrial epithelial ovarian cancer, or carcinosarcoma	NCT03395080	Open-label, multicenter, phase II trial	Recurrent epithelial endometrial or epithelial ovarian cancer or carcinosarcoma	DKN-01 600 mg IV±PTX IV in ECS	ORR CTCAEs PK parameters	Completed (no results posted)	111	January 27, 2021
A 3-arm randomized phase II evaluation of cediranib in combination with weekly paclitaxel or olaparib vs weekly paclitaxel chemotherapy for advanced endometrial carcinoma or for disease relapse within 18 months of adjuvant carboplatin-paclitaxel chemotherapy.	NCT03570437 (COPELIA)	Open-label, multicenter, phase II RCT	Advanced or recurrent endometrial carcinoma or carcinosarcoma, at least one prior CHT	· Arm 1: Paclitaxel 80 mg/mq IV d1,8,15q28 for up to six cycles · Arm 2: Paclitaxel 80 mg/mq IV d1,8,15q28 for up to six cycles+ediranib 20 mg PO QD, until PD or unacceptable toxicity · Am 3: Cediranib 20 mg PO QD+olaparib 300 mg PO Twice daily, until PD or unacceptable toxicity	PFS	Active, not recruiting	124	June 30, 2023
Dose escalation and expansion clinical study to evaluate the safety and efficacy of ELU001 in subjects who have advanced, recurrent or refractory FRα overexpressing tumors	NCT05001282	Open-label, multicenter, single-arm, two-stage, phase I/II trial	Advanced, recurrent, or refractory FRα-overexpressing tumors	Dose escalation: escalating doses of ELU001 Dose expansion:RP2D	MTD RP2D	Recruiting	166	March 15, 2025
A phase II trial of ZW25 in HER2 overexpressed advanced endometrial cancers and carcinosarcomas (ZW25-IST-2)	NCT04513665	Open-label, multicenter, single-arm, two-stage, phase II trial	Recurrent or persistent HER2 overexpressing endometrial cancer or endometrial carcinosarcoma, 1–2 prior CHT	ZW25 (Zanidatamab) 20 mg/kg IV every 2 weeks	ORR	Recruiting	25	April 12, 2023
SYD985 in patients with HER2-expressing recurrent, advanced or metastatic endometrial carcinoma	NCT04205630	A single-arm phase II trial	Recurrent or persistent HER2 overexpressing endometrial cancer, 1 prior platinum-based CHT	SYD985, Intravenous, every 3 weeks (Q3W)	ORR	Active, not recruiting	60	December, 2022
A phase II study of T-DXd in patients with selected HER2 expressing tumors (DPT02)	NCT04482309 DESTINY-PanTumor02	Open-label, multicenter, single-arm, two-stage, phase II trial	Seven cohorts of urothelial bladder cancer, biliary tract cancer, cervical cancer, endometrial cancer, ovarian cancer, pancreatic cancer, and rare tumors.	Trastuzumab deruxtecan by intravenous infusion	ORR	Active, not recruiting	268	June 16, 2023
Phase I trial of intravenous administration of vesicular stomatitis virus genetically engineered to express thyroidal sodium iodide symporter (NIS) and human interferon β, in patients with metastatic or recurrent endometrial cancer	NCT03120624	Open-label, multicenter, phase I RCT	Metastatic or recurrent endometrial cancer	VSV-hIFNbeta-NIS with or without ruxolitinib phosphate	MTD CTCAEs	Recruiting	77	July 15, 2023
A phase I/II study to evaluate the safety, pharmacokinetics, and efficacy of BLU-222 as a single agent and in combination therapy for patients with advanced solid tumors	NCT05252416 (VELA)	Open-label, multicenter, phase I/II trial	Advanced solid tumors	· Arm 1: BLU-222 · Arm 2: BLU-222+carboplatin · Arm 3: BLU-222+ribociclib+fulvestrant · Arm 4: BLU-222+fulvestrant	MTD RP2D ORR CTCAEs	Recruiting	366	September 2026
ATARI: ATR Inhibitor in combination With olaparib in gynecological cancers with ARId1A loss	NCT04065269 (ATARI)	Open-label, multicenter, two-stage, phase II trial	Progressive or recurrent gynecological cancers with ARId1A loss	AZD6738+olaparib	ORR	Recruiting	40	March 2023
Phase I study of the CDK4/6 inhibitor palbociclib (PD-0332991) in combination with the PI3K/mTOR inhibitor gedatolisib (PF-05212384) for patients with advanced squamous cell lung, pancreatic, head and neck, and other solid Tumors	NCT03065062	Open-label, multicenter, two-stage, phase I trial	Advanced solid tumors	Palbociclib PO QD on days 1 to 21 for each of the 4-week cycles Gedatolisib IV once weekly on the first day for each of the 4 weeks during the 4-week cycles.	MTD RP2D CTCAEs	Recruiting	96	January, 2024

*Data extracted by clinicaltrials.gov.104
AE, adverse events; AUC, area under curve; CBDCA, carboplatin; CHT, chemotherapy; CTCAEs, Common Terminology Criteria for Adverse Events; DCR, disease control rate; DLT, dose-limiting toxicities; DOR, duration of response; EC, endometrial cancer; ECD, estimated completion date; ECS, endometrial carcinosarcoma; HER2, human epidermal growth factor receptor 2; ICT, investigator choice of therapy; IV, intravenous; MTD, maximum tolerated dose; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS6, progression-free survival at 6 months; PFS, progression-free survival; PK, pharmacokinetics; PO, per os; PR, partial response; PTX, clpaitaxel ; RCT, randomized clinical trial; RDE, recommended dose of expansion; RP2D, recommended phase 2 dose; SD, stable disease; TGF-β, transforming growth factor β; USC, uterine serous carcinoma.