A randomized, open Phase III study of INCB123667 compared to chemotherapy selected by the investigator in participants with platinum-resistant ovarian cancer with Cyclin E1 overexpression (MAESTRA 2)
Descrizione riassuntiva dello studio
Cell growth and division in the body typically occur in a controlled manner through a process known as the cell cycle. A protein called Cyclin E1, along with another protein called Cyclin-dependent kinase 2 (CDK2), helps regulate this process. Together, these proteins support cells in growing and dividing normally. In some cancers, including ovarian cancer, Cyclin E1 can be present in larger amounts, which is referred to as Cyclin E1 overexpression. This leads to over-stimulation of CDK2, causing uncontrolled cell growth, which in turn leads to tumor growth. INCB123667 has been developed to block CDK2, potentially slowing or stopping the growth of cancer cells that rely on high levels of Cyclin E1. The aim of this study is to assess the efficacy, safety, and tolerability of INCB123667 compared to the standard chemotherapy selected by the investigator (Paclitaxel, pegylated liposomal Doxorubicin [PLD], Gemcitabine, or Topotecan) in participants with ovarian cancer that no longer responds to platinum-based treatments (referred to as platinum-resistant ovarian cancer or PROC) and exhibits Cyclin E1 overexpression.
(BASEC)
Intervento studiato
Objectives and endpoints
Comparison of the efficacy of INCB123667 with the efficacy of standard chemotherapy in participants with platinum-resistant ovarian cancer (PROC) with Cyclin E1 overexpression.
Progression-free survival: Date of study enrollment until the date when the tumor is demonstrably growing or spreading, or until death from any cause (whichever occurs first).
Experts outside the study, who are unaware of the treatment of participants, assess tumor changes based on a standard set of guidelines (referred to as RECIST criteria V.1.1).
Overall survival: Date of study enrollment until death from any cause.
Comparison of the efficacy of INCB123667 with the efficacy of standard chemotherapy in participants with PROC with Cyclin E1 overexpression.
Objective response: A complete disappearance of the tumor (complete response) or a significant reduction in tumor size (partial response).
Experts outside the study, who are unaware of the treatment of participants, assess this based on a standard set of guidelines (referred to as RECIST criteria V.1.1).
Further comparison of the efficacy of INCB123667 against the efficacy of standard chemotherapy in participants with PROC with Cyclin E1 overexpression.
Duration of response: Time from the first response (complete or partial) until the tumor is demonstrably growing or spreading again or until death from any cause.
Experts outside the study, who are unaware of the treatment of participants, assess tumor changes based on a standard set of guidelines (referred to as RECIST criteria V.1.1).
Progression-free survival: Date of study enrollment until the date when the tumor is demonstrably growing or spreading, or until death from any cause (whichever occurs first).
Objective response: A complete disappearance of the tumor (complete response) or a significant reduction in tumor size (partial response).
Duration of response: Time from the first response (complete or partial) until the tumor is demonstrably growing or spreading again or until death from any cause.
Study design
This is a multicenter, open-label study. Open-label means that the investigator and the participant know which treatment is being administered. The study compares the efficacy, safety, and tolerability of INCB123667 with the efficacy, safety, and tolerability of the standard chemotherapy selected by the investigator in participants with PROC with Cyclin E1 overexpression.
Approximately 466 participants will be randomly assigned in a 1:2 ratio to receive either INCB123667 or the chemotherapy selected by the investigator. Before entering the study and starting treatment, all interested patients must provide tumor tissue (fresh tissue or tissue collected within the last 5 years) for examination of Cyclin E1 overexpression. Imaging scans of the tumor will be performed prior to receiving study treatment, every 6 weeks for the first 36 weeks, and then every 12 weeks. RECIST criteria V1.1 will be used to assess changes in the tumor. Safety will be monitored from the time of signing the patient information and consent form until 30 days after administration of the last dose of study treatment or until the start of a new cancer treatment (whichever occurs first).
Study population
Women aged at least 18 years with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with Cyclin E1 overexpression whose cancer is no longer responding to platinum-based treatment will be included in the study. Participants must have good physical performance status (ECOG performance status 0 or 1), adequate organ function, and laboratory results within the defined limits in the study protocol. Side effects from previous cancer treatments must have resolved to at least grade 1 (mild).
Treatments (interventions)
Participants will be randomly assigned in a 1:1 ratio to receive either INCB123667 or the standard chemotherapy selected by the investigator. Participants receiving INCB123667 will take it twice daily in continuous 28-day cycles for as long as they derive benefit and do not meet criteria for discontinuation of treatment. Participants receiving standard chemotherapy will receive it as an intravenous infusion in either 21- or 28-day cycles for as long as they derive benefit and do not meet criteria for discontinuation of treatment. Participants will undergo regular blood and urine tests, and their cancer will be monitored using imaging techniques.
Ethical considerations including expected benefits and risks of the clinical study
INCB123667 is being evaluated in an ongoing Phase I study (INCB 123667-101) in participants with advanced cancer, including ovarian cancer. Initial safety results indicate that the most common side effects affect the digestive system (such as nausea and vomiting) and the bone marrow (effects on red and white blood cells). Most side effects were reversible and can be treated. Additionally, early signs of efficacy have been observed, particularly in participants with PROC with Cyclin E1 overexpression. These early results suggest that INCB123667 may be a new treatment option for women with this type of ovarian cancer.
Disease or condition being studied: Platinum-resistant ovarian cancer (PROC) with Cyclin E1 overexpression.
Treatment under investigation
The aim of this study is to assess the efficacy, safety, and tolerability of INCB123667 compared to the standard chemotherapy selected by the investigator (Paclitaxel, pegylated liposomal Doxorubicin [PLD], Gemcitabine, or Topotecan) in participants with ovarian cancer that no longer responds to platinum-based treatments (referred to as platinum-resistant ovarian cancer or PROC) and exhibits Cyclin E1 overexpression.
Participants will be randomly assigned in a 1:1 ratio to receive either INCB123667 or the standard chemotherapy selected by the investigator. Participants receiving INCB123667 will take it twice daily in continuous 28-day cycles for as long as they derive benefit and do not meet criteria for discontinuation of treatment. Participants receiving standard chemotherapy will receive it as an intravenous infusion in either 21- or 28-day cycles for as long as they derive benefit and do not meet criteria for discontinuation of treatment. Participants will undergo regular blood and urine tests, and their cancer will be monitored using imaging techniques.
The purpose of the combined IVD study is to describe the use of the device for examining Cyclin E1 expression in the clinical study (INCB123667-305) and to define the rationale, objectives, design, analysis, methodology, monitoring, conduct, and retention of study records.
(BASEC)
Malattie studiate
Platinum-resistant ovarian cancer (PROC) with Cyclin E1 overexpression
(BASEC)
Histological diagnosis of high-grade serous, endometrioid, or clear cell epithelial ovarian, fallopian tube, or primary peritoneal cancer. Presence of platinum-resistant disease. Participants who have previously been treated with only 1 line of platinum-based therapy must have received at least 4 cycles of a platinum-containing treatment regimen. The cancer of participants who previously received 2–4 lines of platinum-based therapy must have progressed during the last treatment or within 6 months after the last dose of platinum. Archived FFPE tumor tissue blocks or slides with tissue sections from samples not older than 5 years must be available. If no tumor tissue is available, the interested patient must be willing to undergo a biopsy before entering the study and starting treatment. Additional inclusion criteria will be discussed and reviewed by the physician. (BASEC)
Criteri di esclusione
1. Endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors with any of these histologies, or low-grade/borderline ovarian cancer. 2. Primary, platinum-refractory disease, defined as progression of cancer during or within 3 months after the last dose of a platinum-containing first-line therapy. 3. Clinically significant or uncontrolled heart disease within 6 months prior to the first dose of study treatment. Additional exclusion criteria will be reviewed by the physician. (BASEC)
Luogo dello studio
Bellinzona, Ginevra, Losanna, Altro
(BASEC)
Frauenfeld
(BASEC)
Sponsor
Incyte Corporation
(BASEC)
Contatto per ulteriori informazioni sullo studio
Persona di contatto in Svizzera
Dr. Ilaria Colombo
+41 7645 28823
ilaria.colombo@cluttereoc.chOncology Institute of Southern Switzerland
(BASEC)
Nome del comitato etico approvante (per studi multicentrici solo il comitato principale)
Commissione d'etica Ticino
(BASEC)
Data di approvazione del comitato etico
21.04.2026
(BASEC)
ID di studio ICTRP
NCT07214779 (ICTRP)
Titolo ufficiale (approvato dal comitato etico)
A Phase 3, Randomized, Open-Label Study of INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum Resistant Ovarian Cancer With Cyclin E1 Overexpression (MAESTRA 2) (BASEC)
Titolo accademico
A Phase 3, Randomized, Open-Label Study of INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (ICTRP)
Titolo pubblico
Study to Evaluate INCB123667 Versus Investigator's Choice of Chemotherapy in Participants With Platinum-Resistant Ovarian Cancer With Cyclin E1 Overexpression (ICTRP)
Malattie studiate
Ovarian Cancer (ICTRP)
Intervento studiato
Drug: INCB123667Drug: Investigator's choice of chemotherapy (ICTRP)
Tipo di studio
Interventional (ICTRP)
Disegno dello studio
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Criteri di inclusione/esclusione
Inclusion Criteria:
- Histological diagnosis of high-grade serous epithelial ovarian, fallopian tube, or
primary peritoneal cancer.
- Have platinum-resistant disease.
- Participants who have only had 1 line of platinum-based therapy must have
received at least 4 cycles of platinum containing regimen.
- Participants who have received 2 to 4 lines of platinum-based therapy must have
progressed on or within 6 months after the last dose of platinum.
- Archival FFPE tumor tissue block or slides from a specimen no older than 5 years
must be available. If not available, participant must be willing to undergo a
pretreatment tumor biopsy.
- Received at least 1 and no more than 4 prior lines of systemic therapy following the
initial diagnosis, after which single-agent chemotherapy is considered an
appropriate next therapeutic option.
- Should have received prior treatment with bevacizumab unless there was a
contraindication for its use.
- Should have received prior treatment with mirvetuximab soravtansine if the tumor is
positive for FRa, unless there is an exception for its use on medical grounds.
- Measurable disease per RECIST v1.1.
Exclusion Criteria:
- Have endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors
containing any of these histologies, or low-grade/borderline ovarian cancer.
- Have primary platinum-refractory disease, defined as progression on or within 3
months after the last dose of first line platinum-containing therapy.
- Clinically significant or uncontrolled cardiac disease within 6 months before the
first dose of study treatment.
- Known active CNS metastases and/or carcinomatous meningitis.
- Known additional malignancy that is progressing or requires active treatment, or
history of other malignancy within 3 years before the first dose of study treatment.
- Clinically significant gastrointestinal abnormalities.
Other protocol-defined Inclusion/Exclusion Criteria may apply. (ICTRP)
non disponibile
Endpoint primari e secondari
Progression-Free Survival (PFS) by BICR;Overall Survival (OS) (ICTRP)
Objective response by BICR;Duration of Response (DOR) by BICR;Progression-Free Survival (PFS) by investigator;Objective response by investigator;DOR by investigator;Treatment Emergent Adverse Events (TEAEs);TEAEs leading to dose interruptions, dose reductions or discontinuation of study treatment;Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 30 (C30) at each postbaseline visit;Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-Core 28 (C28) score at each postbaseline visit;Change from baseline in EQ-5D-5L score at each postbaseline visit (ICTRP)
Data di registrazione
non disponibile
Inclusione del primo partecipante
non disponibile
Sponsor secondari
ENGOT Foundation;GOG Foundation (ICTRP)
Contatti aggiuntivi
Incyte Medical MonitorIncyte Corporation Call Center (US), medinfo@incyte.com, 1.855.463.3463, Incyte Corporation (ICTRP)
ID secondari
2025-522748-42-00, GOG-3137, ENGOT-OV95, INCB123667-305 (ICTRP)
Risultati-Dati individuali dei partecipanti
non disponibile
Ulteriori informazioni sullo studio
https://clinicaltrials.gov/study/NCT07214779 (ICTRP)
Risultati dello studio
Riepilogo dei risultati
non disponibile
Link ai risultati nel registro primario
non disponibile