Clinical Trials /

Study of PF-07248144 in Advanced or Metastatic Solid Tumors

NCT04606446

Description:

This is an open-label, multi center study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-07248144 and early signs of clinical efficacy of PF-07248144 as a single agent and in combination with either fulvestrant or letrozole + palbociclib.

Related Conditions:
  • Breast Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of PF-07248144 in Advanced or Metastatic Solid Tumors
  • Official Title: A Phase 1 Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, Pharmacokinetic, Pharmacodynamic, and Anti-tumor Activity of PF-07248144 in Participants With Advanced or Metastatic Solid Tumors.

Clinical Trial IDs

  • ORG STUDY ID: C4551001
  • NCT ID: NCT04606446

Conditions

  • Locally Advanced or Metastatic ER+ HER2- Breast Cancer
  • Locally Advanced or Metastatic Castration-resistant Prostate Cancer
  • Locally Advanced or Metastatic Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
PF-072481441A Monotherapy Escalation Dose Level 1
FulvestrantFaslodex1B Combination Dose Finding Arm level 1
LetrozoleFemara1B Combination Dose Finding Arm Level 2
PalbociclibIbrance1B Combination Dose Finding Arm Level 2

Purpose

This is an open-label, multi center study to evaluate safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-07248144 and early signs of clinical efficacy of PF-07248144 as a single agent and in combination with either fulvestrant or letrozole + palbociclib.

Detailed Description

      Study has two parts, Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is divided
      into Parts 1A, 1B, and 1C and Part 2 is divided into Parts 2A and 2B. In Part 1A, single
      escalating doses of PF-07248144 alone will be administered to determine the maximum tolerable
      dose (MTD) and select the recommended dose for expansion (RP2D). In Part 1B and 1C,
      PF-07248144 will be administered in combination with either fulvestrant or letrozole +
      palbociclib.

      After the determination of the monotherapy expansion RP2D in Part 1A, PF-07248144 will be
      evaluated in a dose expansion cohort as a monotherapy in Part 2A. After determination of the
      combination RP2D from Part 1B and Part 1C, PF-07248144 in combination with an either
      fulvestrant (Part 1B) or letrozole + palbociclib (Part 1C) may be evaluated in Part 2B. The
      specific combination partners that will be carried forward to Part 2B will be contingent upon
      preclinical evidence, clinical safety and potential efficacy as well as PK and PD data.
    

Trial Arms

NameTypeDescriptionInterventions
1A Monotherapy Escalation Dose Level 1ExperimentalPF-07248144 Monotherapy Escalation
  • PF-07248144
1A Monotherapy Escalation Dose Level 2ExperimentalPF-07248144 Monotherapy Escalation
  • PF-07248144
1A Monotherapy Escalation Dose Level 3ExperimentalPF-07248144 Monotherapy Escalation
  • PF-07248144
1A Monotherapy Escalation Dose Level 4ExperimentalPF-07248144 Monotherapy Escalation
  • PF-07248144
1B Combination Dose Finding Arm level 1ExperimentalPF-07248144 with Fulvestrant Combination Dose Finding
  • PF-07248144
  • Fulvestrant
1B Combination Dose Finding Arm Level 2ExperimentalPF-07248144 with Fulvestrant Combination Dose Finding
  • PF-07248144
  • Letrozole
  • Palbociclib
1C Combination Dose Finding Arm Level 1ExperimentalPF-07248144 with Letrozole + Palbociclib Combination Dose Finding
  • PF-07248144
1C Combination Dose FInding Arm Level 2ExperimentalPF-07248144 with Letrozole + Palbociclib Combination Dose Finding
  • PF-07248144
  • Fulvestrant
  • Letrozole
  • Palbociclib
2A Monotherapy Dose Expansion ArmExperimentalPF-07248144 Monotherapy Dose Expansion
  • PF-07248144
2B Combination Dose Expansion ArmExperimentalPF-07248144 with either Fulvestrant or Letrozole + Palbociclib Dose Expansion
  • PF-07248144

Eligibility Criteria

        Inclusion Criteria:

          -  Disease Characteristics - Breast, Prostate, and Lung Cancer

               -  Part 1A (Monotherapy Dose Escalation) Histological or cytological diagnosis of
                  locally advanced or metastatic ER+HER2- breast cancer, locally advanced or
                  metastatic CRPC, or locally advanced or metastatic NSCLC that is intolerant or
                  resistant to standard therapy or for which no standard therapy is available.

               -  Part 1B and Part 1C (Combination Dose Escalation) Histological or cytological
                  diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants
                  must have progressed after at least 1 prior line of treatment with an endocrine
                  therapy and CDK4/6 inhibitor in the advanced or metastatic setting.

               -  Part 2A (ER+HER2- breast cancer 3L+, monotherapy) Histological or cytological
                  diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants
                  must have progressed after at least 1 prior line of CDK4/6 inhibitor and 2 lines
                  of endocrine therapy.

               -  Part 2B (ER+HER2- breast cancer 2L, combination) Histological or cytological
                  diagnosis of locally advanced or metastatic ER+HER2- breast cancer. Participants
                  must have progressed after first line combination treatment with letrozole +
                  palbociclib.

               -  Participants with ER+HER2- advanced or metastatic breast cancer must have
                  documentation of ER-positive tumor (≥1% positive stained cells) based on most
                  recent tumor biopsy utilizing an assay consistent with local standards.

               -  Participants with ER+HER2- advanced or metastatic breast cancer must have
                  documentation of HER2-negative tumor: HER2-negative tumor is determined as
                  immunohistochemistry score 0/1+ or negative by in situ hybridization
                  (FISH/CISH/SISH/DISH) defined as a HER2/CEP17 ratio <2 or for single probe
                  assessment a HER2 copy number <4.

               -  Female participants with ER+HER2- advanced or metastatic breast cancer considered
                  to be of childbearing potential (or have tubal ligations only) must be willing to
                  undergo medically induced menopause by treatment with the approved LHRH agonist
                  such as goserelin, leuprolide or equivalent agents to induce chemical menopause.

               -  Participants must have at least 1 measurable lesion as defined by RECIST version
                  1.1 that has not been previously irradiated.

               -  Eastern Cooperative Oncology Group (ECOG) Performance Status PS 0 or 1

               -  Female or male patients aged ≥ 18 years (Japan ≥ 20 years).

               -  Adequate renal, liver, and bone marrow function.

               -  Resolved acute effects of any prior therapy to baseline severity or CTCAE Grade 1
                  except for adverse events (AEs) not constituting a safety risk by investigator
                  judgment.

        Exclusion Criteria:

          -  Unmanageable ascites (limited medical treatment to control ascites is permitted, but
             all participants with ascites require review by sponsor's medical monitor).

          -  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.

          -  Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks prior
             to study entry.

          -  Prior irradiation to >25% of the bone marrow.

          -  ECG clinically relevant abnormalities (eg, QTc >470 msec, complete LBBB, second/third
             degree AV block, ST elevation or EKG changes suggesting myocardial infarction or
             active myocardia ischemia).

          -  Therapeutic anticoagulation. However, low molecular weight heparin is allowed. Vitamin
             K antagonists or factor Xa inhibitors may be allowed following discussion with the
             Sponsor.

          -  Known or suspected hypersensitivity or severe allergy to active ingredient/excipients
             of PF-07248144.

          -  Active inflammatory GI disease, refractory and unresolved chronic diarrhea or previous
             gastric resection, lap band surgery or other GI conditions and surgeries that may
             significantly alter the absorption of PF-07248144 tablets. Gastroesophageal reflux
             disease under treatment is allowed.

          -  Pregnant or breastfeeding female participants.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose-limiting toxicities in the Dose Escalation Arms.
Time Frame:Up to 29 days
Safety Issue:
Description:Dose-limiting toxicities (DLTs)

Secondary Outcome Measures

Measure:Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Multiple Dose: Steady state AUC during a dosage interval (τ) (AUCτ,ss) in the Dose Escalation and Dose Finding Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms.
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms.
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessments for PF-07248144
Measure:Best Overall Response (BOR) in participants in the Dose Escalation Arms
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Duration of Response (DOR) in participants enrolled in the Dose Escalation Arms
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Peak concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessment for PF-07248144
Measure:Trough concentrations of PF-07248144 for selected cycles in the Dose Escalation Arms
Time Frame:Up to 24 months
Safety Issue:
Description:Pharmacokinetic (PK) assessment for PF-07248144
Measure:Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm
Time Frame:Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Description:The effect of food on the PK of PF-07248144.
Measure:Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm
Time Frame:Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Description:The effect of food on the PK of PF-07248144.
Measure:AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm
Time Frame:Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days)
Safety Issue:
Description:The effect of food on the PK of PF 07248144.
Measure:Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms
Time Frame:Up to 24 months
Safety Issue:
Description:
Measure:Overall survival (OS) observed in participants enrolled in Dose Expansion Arms
Time Frame:Up to 24 months
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Solid tumors

Last Updated

October 22, 2020