Clinical Trials /

PF-07104091 as a Single Agent and in Combination Therapy

NCT04553133

Description:

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 small cell lung, non small cell lung ovarian and breast cancers.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: PF-07104091 as a Single Agent and in Combination Therapy
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: C4161001
  • NCT ID: NCT04553133

Conditions

  • Small Cell Lung Cancer
  • Ovarian Cancer
  • Triple Negative Breast Cancer
  • Non-small Cell Lung Cancer
  • Human Receptor-positive Human Epidermal Growth Factor Receptor 2

Interventions

DrugSynonymsArms
PF-07104091 monotherapyPF-07104091
PF-07104091 + palbociclibPF-07104091 + palbociclib
PF-07104091 + palbociclib + letrozolePF-07104091 + palbociclib + letrozole

Purpose

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 small cell lung, non small cell lung ovarian and breast cancers.

Detailed Description

      Study C4161001 is a Phase 1, open label, multi dose, multi center, dose escalation, safety,
      pharmacokinetic (PK) and pharmacodynamic study of PF-07104091 in adult patients with advanced
      or metastatic small cell lung cancer (SCLC), advanced platinum resistant epithelial ovarian
      cancer/fallopian tube cancer/primary peritoneal cancer, locally recurrent/advanced or
      metastatic triple negative breast cancer (TNBC), HR-positive HER2-negative advanced or mBC,
      advanced or metastatic non-small cell lung cancer (NSCLC). This two part study will assess
      the safety and tolerability of increasing dose levels of PF-07104091 in Part 1, and establish
      the recommended Phase 2 dose (RP2D) in Part 2.
    

Trial Arms

NameTypeDescriptionInterventions
PF-07104091ExperimentalCDK2 monotherapy
  • PF-07104091 monotherapy
PF-07104091 + palbociclibExperimentalCDK2 + palbociclib
  • PF-07104091 + palbociclib
PF-07104091 + palbociclib + letrozoleExperimentalCDK2 + palbociclib + letrozole
  • PF-07104091 + palbociclib + letrozole

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 up to 3 prior lines of therapy

          -  Participants with cytological diagnosis of advanced/metastatic SCLC

          -  Participants with or cytological diagnosis of advanced/metastatic NSCLC

          -  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

          -  COVID-19/SARS-CoV2

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Escalation: Number of participants with Dose-limiting toxicities (DLT) during first cycle
Time Frame:28 days
Safety Issue:
Description:Number of participants with DLTs, which are typically Grade 3 or higher adverse events will be summarized by dose level

Secondary Outcome Measures

Measure:Maximum plasma concentration (Cmax) of PF-07104091 after a single dose and multiple dose
Time Frame:Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Peak concentration of PF-07104091 during selected cycles
Measure:Time to maximum plasma concentration (Tmax) of PF-07104091 after a single dose and multiple dose
Time Frame:Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:Time to peak concentration of PF-07104091 during selected cycles
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
Time Frame:Day 1 and Day 15 of Cycle 1 (each cycle is 28 days)
Safety Issue:
Description:AUC of PF-07104091 will be calculated at selected cycles
Measure:Area under the curve of PF-07104091 with or without food
Time Frame:From baseline through time to event on study or study completion (approximately 2 years)
Safety Issue:
Description:AUC of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
Measure:Maximum plasma concentration of PF-07104091 with or without food
Time Frame:From baseline through time to event on study or study completion (approximately 2 years)
Safety Issue:
Description:Peak concentrations of PF-07104091 in plasma and whether absorption of the drug is affected when taken by food
Measure:To document any preliminary evidence of antitumor activity of PF-07104091 as a single agen and in combination with palbociclib and in combination with letrozole by objective response rate (ORR) in dose escalation
Time Frame:From baseline and every 8 weeks through disease progression or study completion (approximately 2 years)
Safety Issue:
Description:Percentage of participants with a best overall response of CR or PR using RECIST 1.1
Measure:To document any preliminary evidence of antitumor activity of PF-07104091 by time to event endpoints
Time Frame:From baseline through time to event on study or study completion (approximately 2 years)
Safety Issue:
Description:Time from first assessment of event endpoint to last assessment of using RECIST 1.1

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Small cell lung cancer
  • Ovarian cancer
  • Triple negative breast cancer
  • Human receptor-positive human epidermal growth factor receptor 2
  • Non-small cell lung cancer
  • Cyclin-Dependent Kinase 2 Inhibitor
  • PF-07104091
  • palbociclib
  • letrozole
  • cyclin-dependent kinase
  • Ibrance
  • Femara

Last Updated

September 18, 2020