A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Letrozole Compared to Letrozole Alone in Postmenopausal Women 18 Years or Older With HR-Positive, HER2-Negative Breast Cancer in the Neoadjuvant Setting

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

12 Nov 2024 → 11 Jul 2025

Decision date (initial)

2024-10-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-512848-30-00

ClinicalTrials.gov

NCT06465368

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacogenomic, Pharmacodynamic

Evaluate the effects of PF-07220060 plus letrozole and letrozole alone, respectively, on Ki-67 expression in tumors after 2 weeks of treatment.

Secondary objectives 4

1. Evaluate the safety and tolerability of PF-07220060 plus letrozole and letrozole alone after 2 weeks of treatment.
2. Evaluate ctDNA response on treatment after 2 weeks of treatment.
3. To determine steady-state plasma concentrations of PF-07220060 in combination with letrozole.
4. Determine changes in Ki-67 expression.

Conditions and MedDRA coding

HORMONE RECEPTOR-POSITIVE, HER2-NEGATIVE BREAST CANCER

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Female participants ≥18 years (or the minimum age of consent in accordance with local regulations) with natural or surgical postmenopause at screening
2. Histologically confirmed HR-positive and HER2-negative BC (per local assessment).
3. Must have Ki-67 score ≥10% (analyzed locally).
4. Must have unilateral, invasive T1c-T4c, N0-N2, M0 BC (AJCC; Version 8)
5. ECOG PS 0 or 1.
6. Willingness to undergo a baseline biopsy (if not done previously, which meets the sample collection requirement outlined in Section 8.2.1), and an on-treatment biopsy (per Section 8.7.1)

Exclusion criteria 13

1. Any other active malignancy within 3 years prior to enrollment, except for adequately treated basal cell or squamous cell skin cancer, or cervical carcinoma in situ.
2. Any of the following in the previous 6 months: Myocardial infarction; Severe unstable angina; Coronary/peripheral artery bypass graft; Symptomatic congestive heart failure (New York Heart Association class III or IV); Cerebrovascular accident; Transient ischemic attack; Symptomatic pulmonary embolism or other clinically significant episode of thromboembolism
3. Active inflammatory GI disease, chronic diarrhea, known uncontrolled diverticular disease or previous gastric resection or lap band surgery.
4. History of allergy or reaction to any of the drug components for PF-07220060, letrozole (or other study medications), including participants with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
5. Inability to take oral medication without crushing, dissolving, or chewing tablets.
6. Participants with known active, bacterial, fungal, or viral infection, including (but not limited to) HBV, HCV, and known HIV or AIDS-related illness.
7. Major surgery (as defined by the investigator) within 2 weeks of first dose of study intervention or has not recovered from major side effects.
8. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator’s judgment, make the participant inappropriate for the study.
9. Inadequate bone marrow, renal, and/or liver function
10. Prior and/or current prohibited treatment including: Systemic therapy (eg, chemotherapy, hormonal therapy), radiation, surgery, or any investigational agents for the treatment of BC.; Use of HRT or any other estrogen-containing medication (including vaginal estrogen) within 2 weeks prior to diagnostic tissue sample taken; Any live vaccines within 14 days of planned start of first dose of study intervention.; Current use or anticipated need for use of any prohibited food, supplements or concomitant medication(s) or participants unwilling or unable to use a required concomitant medication(s). Refer to Appendix 9.
11. Previous administration with an investigational product within 2 weeks (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products at any time during their participation in this study.
12. Participants who are involuntarily incarcerated. (Note: Under certain specific circumstances a person who has been imprisoned may be included or permitted to continue as a participant. Strict conditions apply and Sponsor approval is required).
13. Investigator site staff directly involved in the conduct of the study and their family members, site staff otherwise supervised by the investigator, and sponsor and sponsor delegate employees directly involved in the conduct of the study and their family members.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CCCA (Ki-67 ≤2.7%) rates at Day 14 (centrally assessed biopsy).

Secondary endpoints 4

1. Incidence of all AEs, SAEs, and AEs leading to study drug discontinuation.
2. ctDNA measurements at baseline and Day 14.
3. Ctrough and peri-biopsy plasma concentrations of PF-07220060.
4. Ki-67 staining.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 9

Locations

8 EU/EEA countries · 44 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 46 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications