| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HR-positive HER2-negative metastatic/advanced BC |
| CM metastásico/avanzado RH positivo y HER2 negativo |
|
| E.1.1.1 | Medical condition in easily understood language |
| Breast cancer and other solid tumors |
| Cáncer de mama y otros tumores sólidos |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10006187 |
| E.1.2 | Term | Breast cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10055113 |
| E.1.2 | Term | Breast cancer metastatic |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
Part 2:
To assess the safety and tolerability of the combination therapy of PF-07220060, PF-07104091, and ET (fulvestrant for Parts 2A and 2B; letrozole for Part 2C) at the selected RDE in participants with HR-positive HER2-negative advanced or mBC. |
Parte 2:
Evaluar la seguridad y tolerabilidad del tratamiento combinado del PF-07220060, el PF-07104091 y la TE (fulvestrant para las
partes 2A y 2B; letrozol para la parte 2C) en la DRE seleccionada en
participantes con CMM o avanzado RH positivo y HER2 negativo. |
|
| E.2.2 | Secondary objectives of the trial |
Part 2:
To estimate the antitumor activity of PF-07220060, PF-07104091, and ET (fulvestrant for Parts 2A and 2B; letrozole for Part 2C) at the selected RDE in participants with HR-positive HER2-negative advanced or mBC. To further evaluate PK of PF-07220060, PF-07104091 in combination with letrozole or fulvestrant. |
Calcular la actividad antitumoral del PF-07220060, el PF-07104091 y la TE(fulvestrant para las partes 2A y 2B; letrozol para la parte 2C) en la DRE seleccionada en participantes con CMM o avanzado RH positivo y HER2 negativo.
• Evaluar en mayor profundidad la FC del PF-07220060, el PF-07104091 encombinación con letrozol o fulvestrant. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Male and female participants ≥ 18 years of age at Visit 1.
Histological or cytological diagnosis of locally advanced or metastatic solid tumor/diagnosis which is unresectable.
Evaluable lesion (including skin or bone lesion only, Part 1)
Participants entering the study in the expansion cohort have at least 1 measurable lesion as defined by RECIST (version 1.1) that has not been previously irradiated.\
Cancer type:
HR-positive HER2-negative tumor (Part 1 and Part 2)
HR-positive HER2-positive tumor (Part 1)
Advanced solid tumor or metastatic disease (Part 1)
ECOG PS 0 or 1. |
• Participantes hombres y mujeres ≥18 años de edad en la visita 1.
• Diagnóstico histológico o citológico de tumor sólido localmente avanzado o metastásico/diagnóstico irresecable.
• Lesión evaluable (incluida solo la lesión cutánea u ósea, parte 1)
• Los participantes que entren en el estudio en la cohorte de ampliación tienen al menos 1 lesión medible según los RECIST (versión 1.1) que no se ha irradiado con anterioridad.\
• Tipo de cáncer:
• Tumor RH positivo y HER2 negativo (parte 1 y parte 2)
• Tumor RH positivo y HER2 positivo (parte 1)
• Tumor sólido avanzado o enfermedad metastásica (parte 1)
• EF del ECOG 0 o 1. |
|
| E.4 | Principal exclusion criteria |
Prior/concomitant treatment as follows:
- prior treatment with any CDK 4/6 inhibitor, or fulvestrant, or everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway (Part 2B);
- prior neoadjuvant or adjuvant treatment with a non-steroidal AI (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment (Part 2C);
- prior treatment with any CDK4/6 inhibitor for advanced disease (Part 2B and 2C);
- radiation therapy within 4 weeks prior to study enrollment, with the exception of palliative radiotherapy following discussion with the sponsor.
- Inadequate organ function.
- Known bleeding disorders.
- Participation in other studies involving investigational drug(s) within 4 weeks (or 5 half-lives, whichever is shorter) prior to study entry.
- Participants with any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, Bowen’s disease
- Current use or anticipated need for PPI within 14 days prior to first dose of the study intervention. For participants with gastroesophageal reflux disease, concurrent treatment with PPIs is not allowed and treatment with H2 blockers and/or antacids if medically required must be dosed according to protocol guidelines.
- Previous high-dose chemotherapy requiring stem cell rescue.
- Last anticancer treatment within 2 weeks (or 5 half-lives, whichever is shorter, unless the last immediate anticancer treatment contained an antibody-based agent(s) (approved or investigational), then the interval of 4 weeks or 5 half-lives (whichever is shorter) is required prior to receiving the study intervention (except in Part 2C where no systemic anticancer treatment in advanced or metastatic setting is allowed). |
Tratamiento previo/concomitante siguientes:
• tratamiento previo con cualquier inhibidor de CDK 4/6, fulvestrant o everólimus, o cualquier fármaco cuyo mecanismo de acción consista en inhibir la vía PI3K-mTOR (parte 2B);
• tratamiento neoadyuvante o adyuvante previo con un IA no esteroideo (p. ej., anastrozol o letrozol) con recidiva de la enfermedad durante o dentro de los 12 meses posteriores al tratamiento (parte 2C);
• tratamiento previo con cualquier inhibidor de CDK4/6 para la enfermedad avanzada (partes 2B y 2C);
• radioterapia dentro de las 4 semanas anteriores a la inscripción en el estudio, a excepción de la radioterapia paliativa tras comentarlo con el promotor.
• Funcionamiento orgánico inadecuado.
• Trastornos hemorrágicos conocidos.
• Participación en otros estudios que impliquen el/los fármaco(s) en investigación en las 4 semanas (o 5 semividas, lo que sea más corto), anteriores a la entrada en el estudio.
• Participantes con cualquier otra neoplasia maligna activa en los 3 años anteriores a la inscripción, excepto carcinoma basocelular o espinocelular, o carcinoma in situ del cuello uterino, enfermedad de Bowen, tratados adecuadamente.
• Uso actual o necesidad prevista de IBP en los 14 días anteriores a la primera dosis del tratamiento del estudio. En el caso de los participantes con enfermedad de reflujo gastroesofágico, no se permite el tratamiento concomitante con IBP. Por otra parte, si el tratamiento con antagonistas H2 o antiácidos es médicamente necesario, las dosis deben administrarse de acuerdo con las directrices del protocolo.
• Quimioterapia anterior a dosis alta que ha requerido rescate de células madre.
• Último tratamiento antineoplásico en el plazo de 2 semanas o 5 semividas (lo que sea más corto), a menos que el último tratamiento antineoplásico inmediato contenga un fármaco o fármacos basados en anticuerpos (aprobados o en investigación), entonces se requiere el intervalo de 4 semanas o 5 semividas (lo que sea más corto) antes de recibir el tratamiento del estudio (excepto en la parte 2, en la que se no se permite seguir un tratamiento antineoplásico sistémico en contextos avanzados o metastásicos). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
• First cycle DLTs.
• AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) timing, seriousness, and relationship to study intervention.
• Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
• Vital sign abnormalities
• Heart rate corrected QT interval (eg, QTcF).
• First cycle DLTs (for the safety run-in).
• AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study treatment.
• Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0, and timing. |
• TLD en el primer ciclo.
• AA caracterizados por tipo, frecuencia, intensidad (según la clasificación CTCAE del NCI, versión 5.0), momento de aparición, gravedad y relación con el tratamiento del estudio.
• Anomalías analíticas caracterizadas por tipo, frecuencia, intensidad (clasificada según los CTCAE del NCI, versión 5.0) y momento de aparición.
• Anomalías en las constantes vitales
• Intervalo QT corregido de la frecuencia cardíaca (p. ej., QTcF). |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
ORR and CBR as assessed using RECIST version 1.1.
TTE endpoints: DoR, PFS, and TTP.
Concentrations of PF-07220060 and PF-07104091 at selected time points. |
• TRO y TBC evaluadasmediante los criterios RECIST, versión 1.1.
• Criterios de valoración de ThA: DR, SSP y THP.
• Concentraciones de PF-07220060 y PF-07104091 en determinados puntos temporales. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 7 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Argentina |
| Brazil |
| Mexico |
| South Africa |
| Bulgaria |
| Spain |
| Czechia |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study is defined as the date of the last visit of the last participant in the study. |
| El final del estudio se define como la fecha de la última visita del último participante en el estudio. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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