The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Clinical Trial Details

Geo Regions

Category

Breast Cancer

Category

Gynecological Cancer

Category

Thoracic Cancer

CDK2 Inhibitor

PF-07104091 is an investigational compound. Its safety and efficacy have not been established.

PHASE 1/2A DOSE ESCALATION, FINDING AND EXPANSION STUDY EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS AND ANTI TUMOR ACTIVITY OF PF-07104091 AS A SINGLE AGENT AND IN COMBINATION THERAPY
Phase 1 /2
NCT04553133

Active enrolling

Globe
Locations

United States, China, Japan, Mexico

Study design

Participant Group/Arm

EXPERIMENTAL: PF-07104091

CDK2 monotherapy dose escalation

Intervention/Treatment

DRUG: PF-07104091 monotherapy dose escalation

PF-07104091 will be administered orally

Participant Group/Arm

EXPERIMENTAL: PF-07104091 + palbociclib + fulvestrant

CDK2 + palbociclib + fulvestrant

Intervention/Treatment

DRUG: PF-07104091 + palbociclib + fulvestrant

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

Participant Group/Arm

EXPERIMENTAL: PF-07104091 + palbociclib + letrozole

CDK2 + palbociclib + letrozole

Intervention/Treatment

DRUG: PF-07104091 + palbociclib + letrozole

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

Participant Group/Arm

EXPERIMENTAL: PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 monotherapy dose expansion (SCLC)

Intervention/Treatment

DRUG: PF-07104091 monotherapy dose expansion (SCLC)

PF-07104091 will be administered orally

Participant Group/Arm

EXPERIMENTAL: PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 monotherapy dose expansion (ovarian)

Intervention/Treatment

DRUG: PF-07104091 monotherapy dose expansion (ovarian)

PF-07104091 will be administered orally

Participant Group/Arm

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

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

Intervention/Treatment

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

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

Participant Group/Arm

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

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

Intervention/Treatment

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

PF-07104091 will be administered orally in combination with fulvestrant

Study design table for Clinical Trial

Key eligibility criteria

Inclusion criteria
  • 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
Exclusion criteria
  • 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.
  • Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life threatening complications in the short
  • Participants with an indwelling catheter that has an external component such as those used for drainage of effusion(s) or central venous catheter that is externally
  • Previous high dose chemotherapy requiring stem cell rescue
  • Known abnormalities in coagulation such as bleeding diathesis, or treatment with anticoagulants precluding intramuscular injections of goserelin (if applicable).
  • Current use or anticipated need for food or drugs that are known strong CYP3A4/5 or UGT1A9 inhibitors or inducers
  • Current use or anticipated need for drugs that are known sensitive UGT1A1 substrates with narrow therapeutic
  • Serum pregnancy test positive at screening
  • Other medical or psychiatric condition

Key dates

Study start date
  • September 2020
Estimated primary completion date
  • January 2026

Key endpoints

Primary Outcome Measures
Outcome Measure

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

Measure Description

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

Time Frame

28 days

Outcome Measure

To evaluate incidence of treatment emergent adverse events and laboratory abnormalities

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Outcome Measure

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

Measure Description

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

Time Frame

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

Primary Outcome Measures table for Clinical Trial
Secondary Outcome Measures:
Outcome Measure

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

Measure Description

Peak concentration of PF-07104091 during selected cycles

Time Frame

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

Outcome Measure

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

Measure Description

Time to peak concentration of PF-07104091 during selected cycles

Time Frame

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

Outcome Measure

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

Measure Description

AUC of PF-07104091 will be calculated at selected cycles

Time Frame

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

Outcome Measure

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

Measure Description

AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food

Time Frame

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

Outcome Measure

Maximum plasma concentration of PF-07104091 with or without food

Measure Description

Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food

Time Frame

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

Outcome Measure

To document any preliminary evidence of 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 escalation

Measure Description

Percentage of participants with a best overall response of CR or PR using RECIST 1.1

Time Frame

From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)

Outcome Measure

To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints

Measure Description

Time from first assessment of event endpoint to last assessment of using RECIST 1.1

Time Frame

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

Secondary Outcome Measures table for Clinical Trial

Number of participants

320

Collaborators and investigators

Sponsor: Pfizer

Collaborator: None

This information is current as of March 10th 2023.
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More Information Close NCT# stands for National Clinical Trial number. This is a unique identification code given to each clinical trial registered on ClinicalTrials.gov. The format is "NCT" followed by an 8-digit number (for example, NCT00000419). Also called the ClinicalTrials.gov identifier. NCT04553133