Study of PF-07248144 in Advanced or Metastatic Solid Tumors
PHASE2RECRUITING
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 other agents.
Study details:
Study has two parts, Part 1 (dose escalation) and Part 2 (dose expansion). Part 1 is divided into Parts 1A, 1B, 1C, 1D and 1E and Part 2 is divided into Parts 2A, 2B, 2D and 2E. 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, 1C, 1D and 1E PF-07248144 will be administered in combination with either fulvestrant (Part 1B); palbociclib + letrozole (Part 1C) or PF-07220060+fulvestrant (Part 1D) or vepdegestrant (Part 1E). 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. After determination of the triple combination RDE from Part 1D, PF-07248144 in combination with PF-07220060 + fulvestrant will be evaluated in a combination dose-expansion cohort, Part 2D. After determination of the combination RDE from Part 1E, PF-07248144 in combination with vepdegestrant will be evaluated in a combination dose-expansion cohort, Part 2E.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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, Part 1C, Part 1D and Part 1E (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, combination with fulvestrant) Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy.. Participants must not have received more than 3 prior lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant.
- Part 2D (ER+HER2- breast cancer 2-4L, combination with PF-07220060 (CDK4i) and fulvestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy. Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have but are not required to have prior treatment with fulvestrant.
- Part 2E (ER+HER2- breast cancer 2-4L, combination with vepdegestrant): Histological or cytological diagnosis of advanced or metastatic ER+HER2- breast cancer. Participants must have progressive disease after at least 1 prior line of a CDK4/6 inhibitor and at least 1 prior line of endocrine therapy; Participants must have not received more than 3 lines of systemic therapies including up to 1 line of cytotoxic chemotherapy for visceral disease in advanced or metastatic setting; Participants may have received fulvestrant.
- 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.
- Female participants with ER+HER2- advanced or metastatic breast cancer of nonchildbearing potential must meet at least 1 criteria of achieving postmenopausal status.
- 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) (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 3 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.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE2
Study ID
NCT04606446
Intervention or treatment
DRUG: PF-07248144
DRUG: Fulvestrant
DRUG: Letrozole
DRUG: Palbociclib
DRUG: PF-07220060
DRUG: PF-07850327, ARV-471, vepdegestrant
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
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
Chris O'Brien Lifehouse
Select from list below to view details:
Chris O'Brien Lifehouse
Camperdown, New South Wales, Australia
Cancer Research South Australia
Adelaide, South Australia, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
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Who is running the clinical trial?
P
Pfizer
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: 1A Monotherapy Dose Escalation
| Drug: PF-07248144 |
EXPERIMENTAL: 1B Combination Dose Escalation
| Drug: PF-07248144, Drug: Fulvestrant |
EXPERIMENTAL: 1C Combination Dose Escalation
| Drug: PF-07248144, Drug: Letrozole, Drug: Palbociclib |
EXPERIMENTAL: 2A Monotherapy Dose Expansion Arm
| Drug: PF-07248144 |
EXPERIMENTAL: 2B Combination Dose Expansion Arm
| Drug: PF-07248144, Drug: Fulvestrant |
EXPERIMENTAL: 1D Combination Dose Escalation
| Drug: PF-07248144, Drug: Fulvestrant, Drug: PF-07220060 |
EXPERIMENTAL: 2D Combination Dose Expansion Arm
| Drug: PF-07248144, Drug: Fulvestrant, Drug: PF-07220060 |
EXPERIMENTAL: China Monotherapy Dose Expansion
| Drug: PF-07248144 |
EXPERIMENTAL: 1E Combination Dose Escalation
| Drug: PF-07248144, Drug: PF-07850327, ARV-471, vepdegestrant |
EXPERIMENTAL: 2E Combination Dose Expansion Arm
| Drug: PF-07248144, Drug: PF-07850327, ARV-471, vepdegestrant |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose-limiting toxicities in the Dose Escalation Arms. | Dose-limiting toxicities (DLTs) | Up to 29 days |
| Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Escalation Arms. | Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. | Up to 24 months |
| Safety and Tolerability through monitoring of laboratory assessments for participants enrolled in the Dose Escalation Arms. | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Up to 24 months |
| Safety and Tolerability as assessed by adverse event monitoring for participants enrolled in the Dose Expansion Arms | Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy. | Up to 24 months |
| Safety and Tolerability through monitoring of laboratory assessments for participants enroled in the Dose Expansion Arms | Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing. | Up to 24 months |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Single Dose: Maximum Observed Concentration (Cmax) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Single Dose: Time to Maximum concentration (Tmax) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Single Dose: AUC from time zero to time of last measurable concentration (AUClast) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Single and Multiple Dose: Terminal Elimination half-life (t1/2) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Multiple Dose: Steady-State Cmax (Cmax,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Multiple Dose: Steady-state Tmax (Tmax,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Multiple Dose: Steady state AUC during a dosage interval (τ) (AUCτ,ss) in the Dose Escalation and Dose Finding Arms | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Multiple Dose: Steady-state Cmin (Cmin,ss) in the Dose Escalation and Dose Finding Arms. | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Multiple Dose: Steady-state apparent total clearance (CLss/F) in the Dose Escalation and Dose Finding Arms. | Pharmacokinetic (PK) assessments for PF-07248144, PF-07220060 (Part 1D) and vepdegestrant and ARV-473 (Part 1E) | Up to 24 months |
| Palbociclib trough concentrations at steady instate (Cmin,ss) in the 1C combination dose finding arm. | Pharmacokinetic (PK) assessment for palbociclib exposure. | Up to 24 months |
| Peak concentrations of PF-07248144, PF-07220060 (Part 2D) and vepdegestrant and ARV-473 (Part 2E) for selected cycles in the Dose Expansion Arms | Pharmacokinetic (PK) assessment for PF-07248144, PF-07220060 (Part 2D) and vepdegestrant and ARV-473 (Part 2E) | Up to 24 months |
| Trough concentrations of PF-07248144 for selected cycles in the Dose Expansion Arms | Pharmacokinetic (PK) assessment for PF-07248144 , PF-07220060 (Part 2D) and vepdegestrant and ARV-473 (Part 2E) | Up to 24 months |
| Maximum Observed Concentration (Cmax) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF-07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) |
| Time to Maximum concentration (Tmax) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF-07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) |
| AUC from time zero to time of last measurable concentration (AUClast) in the participants in the food effect subset in monotherapy dose expansion arm | The effect of food on the PK of PF 07248144. | Cycle 1 Day -7 and Cycle 1 Day 1 (each cycle is 28 days) |
| Amount of PF-07248144 excreted in urine relative to dose administered (%) in a sub-set of participants in monotherapy dose expansion arm. | Evaluate urine pharmacokinetic (PK) of PF-07248144. | Up to 24 months |
| Renal clearance (CLr) in a sub-set of participants in monotherapy dose expansion arm | Evaluate urine pharmacokinetic (PK) of PF-07248144. | Up to 24 months |
| Progression Free Survival (PFS) observed in participants in the Dose Expansion Arms | Not Specified | Up to 24 months |
| Time to Progression (TTP) observed in participants enrolled in the Dose Expansion Arms | Not Specified | Up to 24 months |
| Overall survival (OS) observed in participants enrolled in Dose Expansion Arms | Not Specified | Up to 24 months |
| Best Overall Response (BOR) observed in participants in the dose expansion arms | Not Specified | Up to 24 months |
| Duration of Response (DOR) observed in participants in the dose expansion arms | Not Specified | up to 24 months |
| Clinical Benefit Rate (CBR) observed in participants in the Dose Expansion Arms | Not Specified | up to 24 months |
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References
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