Condition médicale (spécialité visée)
Choix aire thérapeutique
Cancérologie / Radio-oncologie/ tumeurs solides
Stades de cancer
Avancé
Autre
Platinum-Resistant Ovarian Cancer
Biomarqueur
Autre
Cyclin E1
Profil des participants
Limites d'âge
Sexe(s) des participants
Femmes
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion :
* Diagnostic histologique de cancer épithélial séreux de haut grade de l'ovaire, de la trompe de Fallope, ou du péritoine primaire.
* Avoir une maladie résistante au platine.
* Les participants n'ayant eu qu'une seule ligne de thérapie à base de platine doivent avoir reçu au moins 4 cycles de régime contenant du platine.
* Les participants ayant reçu de 2 à 4 lignes de thérapie à base de platine doivent avoir progressé lors ou dans les 6 mois suivant la dernière dose de platine.
* Un bloc de tissu tumoral FFPE d'archive ou des lames d'un spécimen datant de moins de 5 ans doivent être disponibles. Si non disponibles, le participant doit être prêt à subir une biopsie tumorale prétraitement.
* Avoir reçu au moins 1 et pas plus de 4 lignes de thérapie systémique après le diagnostic initial, après quoi une chimiothérapie en monothérapie est considérée comme une option thérapeutique suivante appropriée.
* Devrait avoir reçu un traitement antérieur avec du bevacizumab sauf s'il y avait une contre-indication à son utilisation.
* Devrait avoir reçu un traitement antérieur avec du mirvetuximab soravtansine si la tumeur est positive pour FRα, sauf s'il existe une exception à son utilisation pour des raisons médicales.
* Maladie mesurable selon RECIST v1.1.
Critères d'exclusion :
* Avoir une histologie endométrioïde, à cellules claires, mucineuse, ou sarcomateuse, des tumeurs mixtes contenant l'une de ces histologies, ou un cancer de l'ovaire de bas grade/frontière.
* Avoir une maladie primaire réfractaire au platine, définie comme une progression lors ou dans les 3 mois après la dernière dose de thérapie contenant du platine de première ligne.
* Maladie cardiaque cliniquement significative ou non contrôlée dans les 6 mois avant la première dose du traitement de l'étude.
* Métastases CNS actives connues et/ou méningite carcinomateuse.
* Malignité supplémentaire connue qui progresse ou nécessite un traitement actif, ou antécédents d'autres malignités dans les 3 ans avant la première dose du traitement de l'étude.
* Anomalies gastro-intestinales cliniquement significatives.
D'autres critères d'inclusion/exclusion définis par le protocole peuvent s'appliquer.
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 FRα, 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.
Critères d'exclusion
1. Have endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of these histologies, or low-grade/borderline ovarian cancer,
2. Have primary platinum-refractory disease, defined as progression on or within 3 months after the last dose of first-line platinum-containing therapy,
3. Clinically significant or uncontrolled cardiac disease within 6 months before the first dose of study treatment, including but not limited to unstable angina pectoris or acute myocardial infarction, or New York Heart Association Class III or IV cardiac disease, congestive heart failure, and uncontrolled arrhythmia, or other clinically significant heart disease. Participants with a pacemaker and well-controlled rhythm for at least 1 month before the first dose of study treatment are allowed,
4. History or presence of an ECG abnormality that, in the investigator's opinion, is clinically meaningful. Participants with screening QTcF interval > 470 milliseconds are excluded; in the event that a single QTc interval measurement is > 470 milliseconds, the participant may enroll if the average QTc interval length for the 3 ECGs is < 470 milliseconds,
5. For participants assigned to receive PLD only: LVEF below the institutional limit of normal as measured by ECHO or MUGA scan,
6. Known active CNS metastases and/or carcinomatous meningitis. Note: Participants with previously treated and clinically stable brain or CNS metastases (without evidence of progression by imaging for at least 4 weeks before the first dose of study treatment and any neurologic symptoms have returned to baseline), who have no evidence of new or enlarging brain metastasis or CNS edema, and who have not required steroids for at least 7 days before the first dose of study treatment are eligible,
7. 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. Exceptions include: cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year after treatment with curative intent,
8. Participants with laboratory values at screening defined in Table 7,
9. Significant concurrent, uncontrolled medical condition,
10. Clinically significant gastrointestinal abnormality, including the following:
a. Hospitalization for or clinical findings consistent with a gastrointestinal obstruction within 3 months of signing the main ICF or radiographic evidence of gastrointestinal obstruction at the time of screening. Gastrointestinal obstruction from an uncomplicated isolated lesion that has resolved following primary resection within 3 months of consent may be considered on a case-by-case basis in consultation with the medical monitor to determine suitability for participation.
b. Ascites requiring paracentesis more often than every 4 weeks for symptomatic management. Enrollment of participants with an indwelling peritoneal catheter may be considered in consultation with the medical monitor to determine suitability for participation.
c. Abdominal/pelvic fistula that still requires active management.
d. Requirement for enteral or parenteral nutrition.
e. Malabsorption syndromes and prior surgical procedures that might affect the gastrointestinal transit and absorption of orally taken medication.
f. Known endoscopically-determined active gastroduodenal ulcer(s).
g. Gastrointestinal bleeding (e.g. hematemesis, hematochezia, and melena) within 3 months before the first dose of study treatment.
11. For participants assigned to receive paclitaxel only: unresolved > Grade 1 neuropathy,
12. History of thromboembolism while on optimal anticoagulation therapy,
13. History of thromboembolism and having been on therapeutic anticoagulation for less than 2 weeks before the first dose of study treatment,
14. Toxic effects of prior therapy and/or complications from prior surgical intervention that have not improved to ≤ Grade 1 before the first dose of study treatment, with the exception of ≤ Grade 2 alopecia and skin hypo-/hyperpigmentation,
15. Prior treatment with any CDK2 inhibitor,
16. Any prior chemotherapy, biological therapy or targeted therapy within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment,
17. Any major surgery within 28 days before the first dose of study treatment,
18. Any radiation therapy within 14 days before the first dose of study treatment. Note: Radiation-related toxicities must have improved to ≤ Grade 1,
19. Current treatment with another investigational medication or having been treated with an investigational medication other than the study treatment within 5 half-lives or 28 days (whichever is shorter) before the first dose of study treatment,
20. Current use of prohibited medication,
21. For participants assigned to receive INCB123667 only: current treatment with any strong CYP3A4/CYP3A5 inhibitor or inducer (Drug Interaction Database 2024) or having been treated with a strong CYP3A4/CYP3A5 inhibitor or inducer within 5 half-lives or 28 days (whichever is shorter) before the first dose of INCB123667,
22. Known history of HBV infection with detectable HBV DNA. In cases of chronic HBV infection with active disease, HBV DNA ≥ 500 IU/mL during screening is exclusionary. Additionally, these participants are also excluded if they:
• have not been on anti-HBV treatment (per local practice) for a minimum of 14 days before the first dose of study treatment, and
• are not willing to continue on anti-HBV treatment during the study,
23. Known history of HCV infection with detectable HCV RNA.
Note: Participants who have completed treatment for HCV and are HCV RNA negative are eligible,
24. Known history of HIV infection and any of the following:
• CD4+ T-cell count < 350 cells/μL, • Detectable HIV RNA, or
• On an ART regimen containing drugs that are strong CYP3A4/CYP3A5 inhibitors or inducers.
Note: Switching to an alternative ART regimen with drugs that are weak or moderate CYP3A4/CYP3A5 inhibitors or inducers is allowed but must be taken for at least 28 days before the first dose of study treatment,
25. Any other infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment within 1 week before the first dose of study treatment,
26. For participants assigned to receive PLD only: previous clinical diagnosis of noninfectious ILD, including noninfectious pneumonitis,
27. Known hypersensitivity or severe reaction to any component of study drug(s)/treatment or formulation components,
28. Women who are pregnant (including women who may possibly be pregnant based on medical interview by investigators in Japan), breastfeeding, or expecting to conceive, starting with the screening visit through 180 days after the last dose of study treatment. For Japan, women who are breastfeeding and wish to enroll must discontinue breastfeeding at least 90 days before receiving study treatment. They must also refrain from breastfeeding during the course of study and for 90 days after the last dose of study treatment,
29. Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the participant; or interfere with interpretation of study data,
30. The following participants are excluded in France: vulnerable populations according to article L.1121-6 of the French Public Health Code and adults under legal protection or who are unable to express their consent per article L.1121-8 of the French Public Health Code, not affiliated to a social security per article L.1121-8-1 of the French Public Health Code,