Resumen

Evaluar la seguridad y tolerabilidad de dosis crecientes de PF-07104091 y estimar la dosis máxima tolerada (DMT) y/o seleccionar la dosis recomendada para la fase 2 (DRF2) para PF-07104091 como agente único en participantes con cáncer de pulmón de células pequeñas, cáncer de mama y cáncer de ovario avanzados o metastásicos.

Descripción detallada

El estudio C4161001 es un estudio de fase 1, abierto, de dosis múltiples, multicéntrico, de escalamiento de dosis, seguridad, farmacocinética (FC) y farmacodinámica de PF-07104091 en pacientes adultos con cáncer de pulmón de células pequeñas (CPCP) avanzado o metastásico, cáncer epitelial de ovario/cáncer de trompa de Falopio/cáncer peritoneal primario avanzado resistente al platino, cáncer de mama triple negativo (CMTN) localmente recurrente/avanzado o metastásico, cáncer de mama avanzado o metastásico RH-positivo HER2-negativo, cáncer de pulmón de células no pequeñas (CPCNP) avanzado o metastásico. Este estudio de dos partes evaluará la seguridad y tolerabilidad de niveles de dosis crecientes de PF-07104091 en la Parte 1, y establecerá la dosis recomendada para la fase 2 (DRF2) en la Parte 2.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

Participants with HR-positive HER2-negative advanced or metastatic breast cancer (received at least two prior lines in the advanced or metastatic setting including one prior line of combined CDK4/6 inhibitor and endocrine therapy and no more than two prior lines of cytotoxic chemotherapy)
Participants with locally recurrent/advanced or metastatic TNBC who have received up to 2 prior lines of chemotherapy in the advanced or metastatic setting
Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven) who have received at least 1 systemic anti-cancer therapy containing a platinum analog
Participants with cytological diagnosis of advanced/metastatic SCLC
Participants with or cytological diagnosis of advanced/metastatic NSCLC
Participants with HR-positive HER2-negative advanced or metastatic breast cancer (second line plus setting) (histologically or cytologically proven).
Participants entering the study in the expansion cohort have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated
Performance Status 0 or 1
Adequate bone marrow, hematological, kidney and liver function
Resolved acute effects of any prior therapy to baseline severity

Criterios de exclusión

Participants with known symptomatic brain metastases requiring steroids
Participants with any other active malignancy within 3 years prior to enrollment
Major surgery within 3 weeks prior to study entry
Radiation therapy within 3 weeks prior to study entry.
Systemic anti cancer therapy within 4 weeks prior to study
Prior irradiation to \>25% of the bone marrow
Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, and known HIV or AIDS related illness
Active COVID-19/SARS-CoV2 infection
Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, arrhythmias, serious conduction system abnormalities, unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo embolic disease.
Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed.
Hypertension that cannot be controlled by medications
Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.
Known or suspected hypersensitivity to active ingredient/excipients in PF 07104091.
Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short
Participants with an indwelling catheter that has an external component such as those used for drainage of effusion(s) or central venous catheter that is externally
Previous high dose chemotherapy requiring stem cell rescue
Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin (if applicable).
Current use or anticipated need for food or drugs that are known strong CYP3A4/5 or UGT1A9 inhibitors or inducers
Current use or anticipated need for drugs that are known sensitive UGT1A1 substrates with narrow therapeutic
Serum pregnancy test positive at screening
Other medical or psychiatric condition

Intervenciones

drug

PF-07104091 monotherapy dose escalation

PF-07104091 will be administered orally

drug

PF-07104091 + palbociclib + fulvestrant

PF-07104091 will be administered orally in combination with palbociclib and fulvestrant

drug

PF-07104091 + palbociclib + letrozole

PF-07104091 will be administered orally in combination with palbociclib and letrozole

drug

PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 will be administered orally

drug

PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 will be administered orally

drug

PF-07104091 + Fulvestrant (post CDK4/6)

PF-07104091 will be administered orally in combination with fulvestrant

drug

PF-0704091 + Fulvestrant (post CDK4/6)

PF-07104091 + fulvestrant (post 4/6) dose expansion

ESTUDIO DE FASE 1/2A DE ESCALAMIENTO DE DOSIS, DETERMINACIÓN DE DOSIS Y EXPANSIÓN QUE EVALÚA LA SEGURIDAD, TOLERABILIDAD, FARMACOCINÉTICA, FARMACODINÁMICA Y ACTIVIDAD ANTITUMORAL DE PF-07104091 COMO AGENTE ÚNICO Y EN TERAPIA COMBINADA

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

PF-07104091 monotherapy dose escalation

PF-07104091 + palbociclib + fulvestrant

PF-07104091 + palbociclib + letrozole

PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 + Fulvestrant (post CDK4/6)

PF-0704091 + Fulvestrant (post CDK4/6)

Ubicaciones

Centro Oncologico Korben

Fundación Cenit Para La Investigación En Neurociencias

Centro Polivalente de Asistencia e Investigacion Clinica - CER San Juan

Patrocinadores