Condition médicale (spécialité visée)
Choix aire thérapeutique
Cancérologie / Radio-oncologie/ tumeurs solides
Stades de cancer
Non applicable
Biomarqueur
Non applicable
Profil des participants
Limites d'âge
Sexe(s) des participants
TOUS
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion :
* Participants masculins et féminins âgés d'au moins 18 ans au moment de la signature du formulaire de consentement éclairé (ICF).
* Cholangiocarcinome histologiquement ou cytologiquement confirmé, non traité auparavant et considéré comme non résécable et/ou métastatique (Stade IV selon le manuel de stadification du cancer de l'American Joint Committee on Cancer (AJCC)).
* Maladie mesurable ou évaluable radiographiquement par CT ou IRM selon les critères RECIST v1.1.
* Statut de performance de l'Eastern Cooperative Oncology Group de 0 à 1.
* Réarrangement FGFR2 documenté.
* Volonté d'éviter une grossesse ou de procréer.
Critères d'exclusion :
* Avoir reçu un traitement systémique anticancéreux antérieur pour une maladie non résécable et/ou métastatique (ne comprenant pas le traitement adjuvant/néo-adjuvant terminé au moins 6 mois avant l'inscription, et les participants ayant reçu un traitement pour une maladie localement avancée avec chemoembolisation trans-artérielle ou radiothérapie interne sélective, si des preuves claires de progression radiologique sont observées avant l'inscription, ou inscrits à partir de l'Amendement 6 (ou Amendement 5-JP2) et le participant a reçu 1 cycle de gemcitabine plus cisplatine \[le début du traitement à l'étude {Cycle 1 Jour 1} doit être au moins 14 jours et ≤ 4 semaines {28 jours} après la dernière dose de gemcitabine plus cisplatine\]).
* Child-Pugh B et C.
* Toxicités liées aux thérapies antérieures doivent être ≤ Grade 1 selon les Critères Terminologiques Communs pour les Événements Indésirables (CTCAE) v5.0 au moment du dépistage.
* Thérapie anticancéreuse concomitante, autre que les thérapies testées dans cette étude.
* Le participant est candidat à une chirurgie potentiellement curative.
* Présence actuelle de trouble cornéen ou rétinien cliniquement significatif (y compris mais non limité à la kératopathie bulleuse/bande, abrasion cornéenne, inflammation/ulcération, et kératoconjonctivite) ou trouble rétinien (y compris mais non limité à la rétinopathie séreuse centrale, dégénérescence maculaire/rétinienne, rétinopathie diabétique, décollement de la rétine) confirmé par examen ophtalmologique.
* Radiothérapie administrée dans les 4 semaines précédant l'inscription/randomisation/première dose du traitement de l'étude.
* Métastases du système nerveux central (SNC) connues ou antécédents de crises non contrôlées.
* Malignité supplémentaire connue qui progresse ou nécessite un traitement actif (exceptions : carcinome basocellulaire de la peau, carcinome épidermoïde de la peau, ou cancer du col utérin in situ ayant subi un traitement potentiellement curatif).
* Valeurs de laboratoire lors du dépistage en dehors de la plage définie par le protocole.
* Antécédents de trouble de l'hémostase du calcium et du phosphate ou déséquilibre minéral systémique avec calcification ectopique des tissus mous (exception : calcifications communément observées dans les tissus mous, tels que la peau, les reins, les tendons ou les vaisseaux en raison de blessures, de maladies et du vieillissement, en l'absence de déséquilibre minéral systémique).
* Troubles gastro-intestinaux significatifs susceptibles d'interférer avec l'absorption, le métabolisme ou l'excrétion du pemigatinib.
* Maladie cardiaque cliniquement significative ou non contrôlée.
* Antécédents ou présence d'un ECG anormal, qui, selon l'avis de l'investigateur, est cliniquement significatif.
* Maladie infectieuse chronique ou actuellement active nécessitant un traitement systémique antibiotique, antifongique ou antiviral dans les 2 semaines précédant l'inscription (les participants avec des infections chroniques asymptomatiques sous traitement prophylactique sont autorisés). Note : les participants positifs au VIH sont autorisés si tous les critères suivants sont respectés : compte CD4+ ≥ 300/µL, charge virale indétectable, recevant un traitement antirétroviral qui n'interagit pas avec le médicament à l'étude, et aucune infection opportuniste associée au VIH/SIDA au cours des 12 derniers mois.
* Utilisation de tout inhibiteur puissant du CYP3A4 ou inducteurs ou inducteurs modérés du CYP3A4 dans les 14 jours ou 5 demi-vies (selon la durée la plus longue) avant la première dose du traitement à l'étude. Note : les inhibiteurs modérés du CYP3A4 ne sont pas interdits
* Hypersensibilité connue ou réaction sévère au pemigatinib, à la gemcitabine, au cisplatine ou à leurs excipients.
* Récupération inadéquate des toxicités et/ou complications d'une chirurgie majeure avant le début du traitement.
Inclusion Criteria:
* Male and female participants at least 18 years of age at the time of signing the informed consent form (ICF).
* Histologically or cytologically confirmed cholangiocarcinoma that is previously untreated and considered unresectable and/or metastatic (Stage IV per the American Joint Committee on Cancer (AJCC) Cancer Staging Manual).
* Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria.
* Eastern Cooperative Oncology Group performance status 0 to 1.
* Documented FGFR2 rearrangement.
* Willingness to avoid pregnancy or fathering children.
Exclusion Criteria:
* Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin \[the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin\]).
* Child-Pugh B and C.
* Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening.
* Concurrent anticancer therapy, other than the therapies being tested in this study.
* Participant is a candidate for potentially curative surgery.
* Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination.
* Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment.
* Known central nervous system (CNS) metastases or history of uncontrolled seizures.
* Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy).
* Laboratory values at screening outside the protocol-defined range.
* History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance).
* Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib.
* Clinically significant or uncontrolled cardiac disease.
* History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful.
* Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months.
* Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment. Note: Moderate CYP3A4 inhibitors are not prohibited
* Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients.
* Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
Critères d'exclusion
Received prior anticancer systemic therapy for unresectable and/or metastatic disease (not including adjuvant/neo-adjuvant treatment completed at least 6 months prior to enrollment, and participants that have received treatment for locally advanced disease with trans-arterial chemoembolization or selective internal radiation therapy, if clear evidence of radiological progression is observed before enrollment, or enrolled as of Amendment 6 (or Amendment 5-JP2) and the participant received 1 cycle of gemcitabine plus cisplatin [the start of study drug {Cycle 1 Day 1} must be at least 14 days and ≤ 4 weeks {28 days} from the last dose of gemcitabine plus cisplatin]),
Child-Pugh B and C,
Toxicities related to prior therapy(ies) must be Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1 at the time of screening,
Concurrent anticancer therapy, other than the therapies being tested in this study,
Participant is a candidate for potentially curative surgery,
Current evidence of clinically significant corneal (including but not limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, and keratoconjunctivitis) or retinal disorder (including but not limited to central serous retinopathy, macular/retinal degeneration, diabetic retinopathy, retinal detachment) as confirmed by ophthalmologic examination,
Radiation therapy administered within 4 weeks of enrollment/randomization/first dose of study treatment,
Known central nervous system (CNS) metastases or history of uncontrolled seizures,
Known additional malignancy that is progressing or requires active treatment (exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy),
Laboratory values at screening outside the protocol-defined range,
History of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues (exception: commonly observed calcifications in soft tissues, such as the skin, kidney, tendons or vessels due to injury, disease, and aging, in the absence of systemic mineral imbalance),
Significant gastrointestinal disorders that could interfere with absorption, metabolism, or excretion of pemigatinib,
Clinically significant or uncontrolled cardiac disease,
History or presence of an abnormal ECG, which, in the investigator's opinion, is clinically meaningful,
Chronic or current active infectious disease requiring systemic antibiotics or antifungal or antiviral treatment within 2 weeks prior to enrollment (participants with asymptomatic chronic infections on prophylactic treatment are allowed). Note: HIV-positive participants are allowed if all of the following criteria are met: CD4+ count ≥ 300/µL, undetectable viral load, receiving antiretroviral therapy that does not interact with study drug, and no HIV/AIDS-associated opportunistic infection in the last 12 months,
Use of any potent CYP3A4 inhibitors or inducers or moderate CYP3A4 inducers within 14 days or 5 half-lives (whichever is longer) before the first dose of study treatment. Note: Moderate CYP3A4 inhibitors are not prohibited,
Known hypersensitivity or severe reaction to pemigatinib, gemcitabine, cisplatin, or their excipients,
Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy,