| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| HR-positive HER2-negative metastatic/advanced BC |
|
| E.1.1.1 | Medical condition in easily understood language |
| Breast cancer and other solid tumors |
|
| 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 1: Combination of PF-07220060 and PF-07104091 Dose Escalation
• To assess the safety and tolerability of increasing doses of PF-07220060 and PF-07104091 as a combination treatment in participants with advanced solid tumors, in order to estimate MTD and select the RDE.
Part 2: Combination of PF-07220060 and PF-07104091 and ET Dose Expansion
• 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(s) in participants with HR-positive HER2-negative advanced or mBC.
|
|
| E.2.2 | Secondary objectives of the trial |
Part 1: Combination of PF-07220060 and PF-07104091 Dose Escalation
• To evaluate PK of PF-07220060 and PF-07104091 when given in combination.
• To evaluate PK of PF 07220060 and PF 07104091 when given in combination, with food.
• To assess tolerability of PF 07220060 and PF 07104091 when given in combination, with food.
• To document any preliminary evidence of anti-tumor activity of PF-07220060 in combination with PF-07104091 in participants with advanced solid tumors.
Part 2: Combination of PF-07220060 and PF-07104091 and ET Dose Expansion
• 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(s) 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. |
|
| 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. |
|
| 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 7 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 (Section 6.8.7).
• 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). |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Part 1: Combination of PF-07220060 and PF-07104091 Dose Escalation
• 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).
Part 2: Combination of PF-07220060 and PF-07104091 and ET Dose Expansion
• 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. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
Part 1: Combination of PF-07220060 and PF-07104091 Dose Escalation
PK parameters of PF-07220060 & PF-07104091:
• Single dose (PF-07104091) - Cmax, Tmax, AUClast, and as data permit, AUCinf, CL/F, Vz/F, and t1/2.
• Multiple Dose (PF-07220060 & PF-07104091; assuming steady state is achieved) - Css,max, Tss,max, AUCss,τ, Css,min, CLss/F, and as data permit, Vss/F, t1/2, and Rac (AUCss,τ/AUCsd,τ) for PF-07104091.
• 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.
• ORR, as assessed using RECIST version 1.1.
• TTE endpoints: eg, DoR, PFS, and TTP.
Part 2: Combination of PF-07220060 and PF-07104091 and ET Dose Expansion
• 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. |
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| 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 | Yes |
| 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 | Yes |
| E.6.13.1 | Other scope of the trial description |
| Tolerability, Anti-tumor activity |
|
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| 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 | Information not present in EudraCT |
| 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 |
| Czechia |
| Spain |
|
| 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. |
|
| 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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