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. (KAT6)

  • STATUS
    Recruiting
  • End date
    Oct 24, 2025
  • participants needed
    108
  • sponsor
    Pfizer
Updated on 23 October 2022

Summary

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.

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 (RDE). In Part 1B and 1C, PF-07248144 will be administered in combination with either fulvestrant or letrozole + palbociclib. After the determination of the monotherapy RDE in Part 1A, PF-07248144 will be evaluated in a dose expansion cohort as a monotherapy in Part 2A.

After determination of the combination RDE from Part 1B, PF-07248144 in combination with fulvestrant, PF-07248144 will be evaluated in a combination dose expansion with fulvestrant in Part 2B. In Part 1C, PF-07248144 in combination with letrozole + palbociclib will be evaluated for dose finding to determine the MTD and RDE for this combination.

Details
Condition 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
Treatment Letrozole, fulvestrant, Palbociclib, PF-07248144
Clinical Study IdentifierNCT04606446
SponsorPfizer
Last Modified on23 October 2022

Eligibility

Yes No Not Sure

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, CRPC, or 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 2L+, 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 1 line of endocrine therapy
Part 2B (ER+HER2- breast cancer 2-4L, fulvestrant-naive, combination with fulvestrant) Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressed after 1 line of a CDK4/6 inhibitor and 1 line of endocrine therapy
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
Female participants with ER+HER2- advanced or metastatic breast cancer of nonchildbearing potential must meet at least 1 criteria of achieving postmenopausal status
Eastern Cooperative Oncology Group (ECOG) Performance Status PS 0 or 1
Female or male patients aged ≥ 18 years (Japan ≥ 20 years) (South Korea ≥ 19 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
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