A Phase 1b/2 Study of PF-07220060 in Combination with PF-07104091 Plus Endocrine Therapy in Participants with BC and other Advanced Solid Tumors

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

20 Mar 2023 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2023-509504-15-00

EudraCT number

2022-002173-28

ClinicalTrials.gov

NCT05262400

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Others, Pharmacodynamic

Part 1:
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(s).
Part 2:
To assess the safety and tolerability of the combination therapy of PF07220060, PF07104091, and ET (fulvestrant for Parts 2A and 2B; letrozole for Part 2C) at the selected RDE(s) in participants with HRpositive HER2negative advanced or mBC.

Secondary objectives 6

1. Part 1: To evaluate PK of PF-07220060 and PF-07104091 when given in combination.
2. Part 1: To evaluate PK of PF-07220060 and PF-07104091 when given in combination, with food.
3. Part 1: To assess tolerability of PF-07220060 and PF-07104091 when given in combination, with food.
4. Part 1: To document any preliminary evidence of anti-tumor activity of PF-07220060 in combination with PF-07104091 in participants with advanced solid tumors.
5. 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 (s) in participants with HR-positive HER2-negative advanced or mBC.
6. Part 2: To further evaluate PK of PF-07220060, PF-07104091 in combination with letrozole or fulvestrant.

Conditions and MedDRA coding

HR-positive HER2-negative metastatic/advanced BC

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Male and female participants ≥ 18 years of age at Visit 1.
2. Histological or cytological diagnosis of locally advanced or metastatic solid tumor/diagnosis which is unresectable.
3. Evaluable lesion (including skin or bone lesion only, Part 1).
4. 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.
5. Cancer type: • HR-positive HER2negative 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.

Exclusion criteria 8

1. 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.
2. Inadequate organ function.
3. Known bleeding disorders.
4. Participation in other studies involving investigational drug(s) within 4 weeks (or 5 half--lives, whichever is shorter) prior to study entry.
5. 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.
6. 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.
7. Previous high-dose chemotherapy requiring stem cell rescue.
8. 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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 8

1. Part 1: First cycle DLTs.
2. Part 1: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) timing, seriousness, and relationship to study intervention.
3. Part 1: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
4. Part 1: Vital sign abnormalities.
5. Part 1: Heart rate corrected QT interval (eg, QTcF).
6. Part 2: First cycle DLTs (for the safety run-in).
7. Part 2: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study treatment.
8. Part 2: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0, and timing.

Secondary endpoints 8

1. Part 1: PK parameters of PF-07220060 and 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.
2. Part 1: AEs as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0) timing, seriousness, and relationship to study intervention.
3. Part 1: Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
4. Part 1: • ORR, as assessed using RECIST version 1.1.
5. Part 1: TTE endpoints: eg, DoR, PFS, and TTP.
6. Part 2: ORR and CBR as assessed using RECIST version 1.1.
7. Part 2: TTE endpoints: DoR, PFS, and TTP.
8. Part 2: Concentrations of PF-07220060 and PF-07104091 at selected time points.

Investigational products

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

Test 6

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 10

Locations

3 EU/EEA countries · 12 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 39 files

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

Application history

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