A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.

JRCT ID: jRCT2031230677

Registered date:05/03/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: ER+/HER2- advanced or metastatic breast cancer
• Date of first enrollment: 19/02/2024
• Target sample size: 65
• Study type: Interventional

Intervention(s)

Drug: vepdegestrant
Daily oral dosages of vepdegestrant continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days
Other Name: ARV-471 / PF07850327

Drug: PF-07220060
Daily oral dosages of PF-07220060 continuously, dose escalation/de-escalation in Phase 1b until recommended phase 2 dose (RP2D) determined, cycles lasting 28 days

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Phase 1b: Number of Participants With Dose Limiting Toxicities [ Time Frame: 28 days ]
Dose Limiting Toxicities (DLTs) rate for Vepdegestrant in combination with PF-07220060, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).

2.Phase 2: Percentage of Participants With Objective Response by investigator assessment [ Time Frame: Up to approximately 1 year ]
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.

Secondary Outcome

1. Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
2. Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - Hematology and coagulation parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
3. Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
4. Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
5. Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
6. Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities- Hematology and coagulation parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
7. Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
8. Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters) [ Time Frame: First study drug dose through a minimum of 28 Days After Last study drug administration ]
9. Phase 1b: To evaluate antitumor activity of Vepdegestrant in combination with PF-07220060 [ Time Frame: Up to approximately 1 year ]
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.
10. Phase 1b and Phase 2: Duration of Response by investigator assessment. [ Time Frame: Up to approximately 1 year ]
Duration of Response (DoR) is defined for participants with confirmed OR (CR or PR) as the time from the first documentation of OR to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
11. Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment. [ Time Frame: Up to approximately 1 year ]
Clinical Benefit Response (CBR) is defined as the proportion of participants with Best Overall Response of confirmed CR or PR at any time, or Stable Disease (SD) >=24 weeks
12. Phase 1b and Phase 2: Progression Free Survival by investigator assessment. [ Time Frame: Up to approximately 1 year ]
Progression Free Survival (PFS) is defined as the time from the date of first dose of study interventions to the date of first documentation of PD or death due to any cause, whichever occurs first.
13. Phase 1b and Phase 2: Plasma concentrations of Vepdegestrant, ARV-473 and PF-07220060 when given in combination. [ Time Frame: Phase 1b: Pre-dose Day 8; Pre-, 0.5, 1, 2, 4, 6, 8, 12h post-dose Day 15; Pre- and 4-8h post-dose 29; Pre- and 4-8h post-dose Day 43; Pre-dose Days 57, 113 and 169. Phase 2: Pre- and 4-8h post-dose Days 15, 29 and 43; Pre-dose Days 57, 113 and 169 ]
14. Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination [ Time Frame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7 ]
Steady-state Cmax (maximum observed serum concentration of drug [Micrograms per milliliter]) of vepdegestrant, ARV-473, and PF-07220060.
15. Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination [ Time Frame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7 ]
Steady-state Tmax (time taken (in hours) to reach the maximum serum drug concentration) of vepdegestrant, ARV-473, and PF-07220060.
16. Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination [ Time Frame: Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7 ]
Steady-state AUClast (Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) of vepdegestrant, ARV-473, and PF-07220060.
17. Phase 2:ctDNA plasma quantitative changes from pre-treatment [ Time Frame: Phase 2 (each cycle is 28 days): Pre-dose on Day 1 of Cycles 1, 2 and 3 and after last treatment administration. ]
To assess changes from baseline levels in plasma circulating tumor DNA (ctDNA) with treatment and to evaluate potential predictability of their associations with clinical outcomes.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Inclusion Criteria:

* Histological or cytological diagnosis of breast cancer. At time of enrollment this must not be amenable to surgical resection with curative intent (>=1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).
* prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Prior fulvestrant allowed; <=1 prior chemotherapy line (no antibody-drug conjugates permitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines of ET in A/MBC setting and most recent ET-based regimen for >6 months.

1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimen of cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting; Prior fulvestrant allowed.

* Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion as defined by RECIST v1.1. (Phase2) are eligible.
* ECOG PS = 0 or 1 (Phase1b) ; <=2 (Phase2)

Exclude criteria

Exclusion Criteria:

* visceral crisis at risk of life-threatening complications in the short term.
* Any condition precluding an adeguate absorption of study interventions.
* newly diagnosed brain metastases, or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 28 days prior to enrollment in the of study.
* history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix. Inflammatory breast cancer are excluded
* impaired cardiovascular function or clinically significant cardiovascular diseases.
* concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only) and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
* renal impairment, not adequate liver function and/or bone marrow function.
* known active infection

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT06206837