NCT04553133

Brief Summary

To assess the safety and tolerability of increasing doses of PF-07104091 and to estimate the Maximum Tolerated Dose (MTD) and/or select the Recommended Phase 2 dose (RP2D) for PF-07104091 as a single agent in participants with advanced or metastatic small cell lung, breast and ovarian cancers.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
157

participants targeted

Target at P75+ for phase_2

Timeline
8mo left

Started Sep 2020

Longer than P75 for phase_2

Geographic Reach
4 countries

22 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress90%
Sep 2020Dec 2026

First Submitted

Initial submission to the registry

August 21, 2020

Completed
26 days until next milestone

Study Start

First participant enrolled

September 16, 2020

Completed
1 day until next milestone

First Posted

Study publicly available on registry

September 17, 2020

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

May 6, 2026

Status Verified

May 1, 2026

Enrollment Period

6.3 years

First QC Date

August 21, 2020

Last Update Submit

May 4, 2026

Conditions

Keywords

Hormone receptor-positive human epidermal growth factor receptor 2 negative breast cancerCyclin-Dependent Kinase 2 InhibitorPF-07104091palbociclibletrozolecyclin-dependent kinaseIbrance

Outcome Measures

Primary Outcomes (6)

  • Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle

    Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level

    28 days

  • To evaluate incidence of treatment emergent adverse events and laboratory abnormalities

    Type, incidence, severity, timing, seriousness and relationship to study treatment of adverse events and any laboratory abnormalities will be summarized by dose level

    From baseline until end of study treatment or study completion (approximately 2 years)

  • Evaluate pulse rate that is out of normal range and changes in pulse rate as compared to baseline

    Identify pulse rate readings that are outside the normal range. The number and percentage of participants who experienced significant pulse rate change from baseline will be summarized by dose level

    From baseline until end of study treatment or study completion (approximately 2 years)

  • Evaluate blood pressure that is out of normal range and changes in blood pressure as compared to baseline

    Identify systolic and diastolic readings that are outside the normal range. The number and percentage of participants who experienced significant blood pressure change from baseline will be summarized by dose level

    From baseline until end of study treatment or study completion (approximately 2 years)

  • To evaluate heart rate corrected QT interval and changes in corrected QT interval as compared to baseline

    Determine the effect of the drug on QT prolongation. The number and percentage of participants who experienced QT interval prolongation will be summarized by dose level

    From baseline until end of study treatment or study completion (approximately 2 years)

  • To evaluate the preliminary antitumor activity of PF-07104091 as a single agent and in combination with palbociclib and in combination with letrozole or fulvestrant or fulvestrant alone by objective response rate (ORR) in dose expansion

    Percentage of participants with a best overall response of complete response (CR) or partial response (PR) using RECIST 1.1

    From baseline through disease progression or study completion (approximately 2 years)

Secondary Outcomes (7)

  • Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose

    Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)

  • Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose

    Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)

  • Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07104091

    Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)

  • Area under the curve of PF-07104091 with or without food

    From baseline through time to event on study or study completion (approximately 2 years)

  • Maximum plasma concentration of PF-07104091 with or without food

    From baseline through time to event on study or study completion (approximately 2 years)

  • +2 more secondary outcomes

Study Arms (7)

PF-07104091

EXPERIMENTAL

CDK2 monotherapy dose escalation

Drug: PF-07104091 monotherapy dose escalation

PF-07104091 + palbociclib + fulvestrant

EXPERIMENTAL

CDK2 + palbociclib + fulvestrant

Drug: PF-07104091 + palbociclib + fulvestrant

PF-07104091 + palbociclib + letrozole

EXPERIMENTAL

CDK2 + palbociclib + letrozole

Drug: PF-07104091 + palbociclib + letrozole

PF-07104091 monotherapy dose expansion (SCLC)

EXPERIMENTAL

PF-07104091 monotherapy dose expansion (SCLC)

Drug: PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 monotherapy dose expansion (ovarian)

EXPERIMENTAL

PF-07104091 monotherapy dose expansion (ovarian)

Drug: PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 + fulvestrant (post CDK4/6) dose expansion

EXPERIMENTAL

PF-07104091 + fulvestrant (post CDK4/6) dose expansion

Drug: PF-0704091 + Fulvestrant (post CDK4/6)

PF-07104091 + fulvestrant (post CDK 4/6) dose escalation

EXPERIMENTAL

CDK2+ fulvestrant (post CDK 4/6) dose escalation

Drug: PF-07104091 + Fulvestrant (post CDK4/6)

Interventions

PF-07104091 will be administered orally

PF-07104091

PF-07104091 + fulvestrant (post 4/6) dose expansion

PF-07104091 + fulvestrant (post CDK4/6) dose expansion

PF-07104091 will be administered orally in combination with palbociclib and fulvestrant

PF-07104091 + palbociclib + fulvestrant

PF-07104091 will be administered orally in combination with palbociclib and letrozole

PF-07104091 + palbociclib + letrozole

PF-07104091 will be administered orally

PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 will be administered orally

PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 will be administered orally in combination with fulvestrant

PF-07104091 + fulvestrant (post CDK 4/6) dose escalation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants with HR-positive HER2-negative advanced or metastatic breast cancer (received at least two prior lines in the advanced or metastatic setting including one prior line of combined CDK4/6 inhibitor and endocrine therapy and no more than two prior lines of cytotoxic chemotherapy)
  • Participants with locally recurrent/advanced or metastatic TNBC who have received up to 2 prior lines of chemotherapy in the advanced or metastatic setting
  • Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC) (histologically or cytologically proven) who have received at least 1 systemic anti-cancer therapy containing a platinum analog
  • Participants with cytological diagnosis of advanced/metastatic SCLC
  • Participants with or cytological diagnosis of advanced/metastatic NSCLC
  • Participants with HR-positive HER2-negative advanced or metastatic breast cancer (second line plus setting) (histologically or cytologically proven).
  • Participants entering the study in the expansion cohort have at least one measurable lesion as defined by RECIST version 1.1 that has not been previously irradiated
  • Performance Status 0 or 1
  • Adequate bone marrow, hematological, kidney and liver function
  • Resolved acute effects of any prior therapy to baseline severity

You may not qualify if:

  • Participants with known symptomatic brain metastases requiring steroids
  • Participants with any other active malignancy within 3 years prior to enrollment
  • Major surgery within 3 weeks prior to study entry
  • Radiation therapy within 3 weeks prior to study entry.
  • Systemic anti cancer therapy within 4 weeks prior to study
  • Prior irradiation to \>25% of the bone marrow
  • Participants with active, uncontrolled bacterial, fungal, or viral infection, including HBV, HCV, and known HIV or AIDS related illness
  • Active COVID-19/SARS-CoV2 infection
  • Baseline 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
  • Any of the following in the previous 6 months: myocardial infarction, long QT syndrome, Torsade de Pointes, arrhythmias, serious conduction system abnormalities, unstable angina, coronary/peripheral artery bypass graft, symptomatic CHF, New York Heart Association class III or IV, cerebrovascular accident, transient ischemic attack, symptomatic pulmonary embolism, and/or other clinical significant episode of thrombo embolic disease.
  • Anticoagulation with vitamin K antagonists or factor Xa inhibitors is not allowed.
  • Hypertension that cannot be controlled by medications
  • Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry.
  • Known or suspected hypersensitivity to active ingredient/excipients in PF 07104091.
  • Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (22)

Medical Oncology & Hematology Associates DBA Mission Cancer and Blood

Clive, Iowa, 50325, United States

Location

Des Moines Oncology Research Association

Des Moines, Iowa, 50309, United States

Location

Medical Oncology & Hematology Associates DBA Mission Cancer and Blood

Des Moines, Iowa, 50309, United States

Location

Medical Oncology & Hematology Associates DBA Mission Cancer and Blood

Des Moines, Iowa, 50314, United States

Location

Norton Hospital

Louisville, Kentucky, 40202, United States

Location

Norton Cancer Institute, St. Matthews Campus

Louisville, Kentucky, 40207, United States

Location

Norton Cancer Institute, Audubon

Louisville, Kentucky, 40217, United States

Location

Norton Brownsboro Hospital

Louisville, Kentucky, 40241, United States

Location

Norton Cancer Institute, Brownsboro Campus

Louisville, Kentucky, 40241, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute - Chestnut Hill

Newton, Massachusetts, 02459, United States

Location

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Cancer Center (IDS Pharmacy)

Long Island City, New York, 11101, United States

Location

Laura & Isaac Perlmutter Cancer Center - NYU ACC

New York, New York, 10016, United States

Location

NYU Langone Medical Center (Tisch Hospital)

New York, New York, 10016, United States

Location

White Plains Hospital

White Plains, New York, 10601, United States

Location

UVA Breast Care Center

Charlottesville, Virginia, 22911, United States

Location

Centro de Investigaciones Medicas y Desarrollo LC

Buenos Aires, Buenos Aires F.D., 1113, Argentina

Location

Complex Oncology Center - Plovdiv EOOD

Plovdiv, 4004, Bulgaria

Location

Complex Oncology Center - Shumen

Shumen, 9700, Bulgaria

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, Tianjin Municipality, 300060, China

Location

Related Links

MeSH Terms

Conditions

Small Cell Lung CarcinomaOvarian NeoplasmsBreast Neoplasms

Interventions

palbociclibFulvestrantLetrozole

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

EstradiolEstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsEstradiol CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsNitrilesOrganic ChemicalsTriazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Pfizer CT.gov Call Center

    Pfizer

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2020

First Posted

September 17, 2020

Study Start

September 16, 2020

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Last Updated

May 6, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will share

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.

More information

Locations