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Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (CDK4)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04557449
Recruitment Status : Recruiting
First Posted : September 21, 2020
Last Update Posted : January 31, 2022
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

This is a Phase 1, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.

In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D).

In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively).

In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted.

Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A.

Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively.


Condition or disease Intervention/treatment Phase
Liposarcoma CRC Prostate Cancer Breast Neoplasms Adenocarcinoma of Lung Solid Tumors Drug: PF-07220060 Combination Product: Letrozole Combination Product: Fulvestrant Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 118 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description: Part 1A: dose escalation of PF-07220060 Part 1B: dose finding of PF-07220060 in combination with letrozole Part 1C:dose finding of PF-07220060 in combination with fulvestrant Part 1D: food effect assessment of PF-07220060 at RP2D in Part 1A Part 2A: dose expansion of PF-07220060 in combination with letrozole Part 2B: dose expansion of PF-07220060 in combination with fulvestrant
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A PHASE 1/1B STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTI-TUMOR ACTIVITY OF PF-07220060 AS A SINGLE AGENT AND AS PART OF COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Actual Study Start Date : September 23, 2020
Estimated Primary Completion Date : April 11, 2025
Estimated Study Completion Date : April 11, 2025


Arm Intervention/treatment
Experimental: 1A Monotherapy Escalation Arm 1
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1A Monotherapy Escalation Arm 2
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1A Monotherapy Escalation Arm 3
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1A Monotherapy Escalation Arm 4
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1B Combination Dose Finding Arm 1
PF-07220060 with Letrozole combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Letrozole
Endocrine Therapy
Other Name: Femara

Experimental: 1B Combination Dose Finding Arm 2
PF-07220060 with Letrozole Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Letrozole
Endocrine Therapy
Other Name: Femara

Experimental: 1C Combination Dose Finding Arm 1
PF-07220060 with Fulvestrant Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Fulvestrant
Endocrine Therapy
Other Name: Faslodex

Experimental: 1C Combination Dose Finding Arm 2
PF-07220060 with Fulvestrant Combination Escalation
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Fulvestrant
Endocrine Therapy
Other Name: Faslodex

Experimental: 2B Combination Dose Expansion
PF-07220060 with Letrozole Combination Expansion
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Letrozole
Endocrine Therapy
Other Name: Femara

Experimental: 2C Combination Dose Expansion
PF-07220060 with fulvestrant Combination Expansion
Drug: PF-07220060
CDK4 inhibitor

Combination Product: Fulvestrant
Endocrine Therapy
Other Name: Faslodex

Experimental: 1D Monotherapy Food Effect
PF-07220060 Monotherapy Food Effect
Drug: PF-07220060
CDK4 inhibitor

Experimental: 1A Monotherapy Escalation Arm 5
PF-07220060 Monotherapy Escalation
Drug: PF-07220060
CDK4 inhibitor




Primary Outcome Measures :
  1. Number of participants with dose limiting toxicities in the Dose Escalation Portion [ Time Frame: Baseline up to day 28 of Cycle 1. ]
    First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C)

  2. Incidence of clinically significant AEs [ Time Frame: Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days ]
    Adverse Events

  3. Incidence of clinically significant laboratory assessments [ Time Frame: Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months ]
    safety laboratory abnormalities

  4. Incidence of clinically significant abnormal vital and ECG parameters [ Time Frame: Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days) ]
    vital signs and heart rate corrected QT interval (Parts 1A, 1B, 1C, 1D)

  5. Food Effect [ Time Frame: Day -7 through the end of Cycle 1 ]
    Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D)


Secondary Outcome Measures :
  1. Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  2. Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  3. Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  4. Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion [ Time Frame: Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  5. Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  6. Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  7. Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  8. Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  9. Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  10. Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  11. Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  12. Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  13. Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  14. Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C)

  15. Tumor Response per RECIST v1.1 [ Time Frame: baseline up to approximately 24 months ]
    Per RECIST v1.1

  16. Duration of Response (DOR) [ Time Frame: baseline up to approximately 24 months ]
    Per RECIST v1.1

  17. Progression Free Survival (PFS) [ Time Frame: baseline up to approximately 24 months ]
    PFS per RECIST v.1.1

  18. Time to Progression (TTP) [ Time Frame: baseline up to approximately 24 months ]
    TTP per RECIST v1.1

  19. Clinical Benefit Rate (CBR) [ Time Frame: baseline up to approximately 24 months ]
    CBR per RECIST v1.1 (Parts 2B, 2C)

  20. Peak and Trough Concentration of PF-07220060 [ Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months ]
    Peak and trough concentration (Parts 2B, 2C)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Part 1: Breast Cancer (BC)

    • Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC
    • Part 1A/Part 1D also include: Refractory HR-positive/HER2-positive BC
  • Part 1: Tumors other than BC (Part 1A/Part 1D): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests
  • Part 2:

    • HR-positive/HER2-negative BC
    • Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C only)
  • Lesion:

    • Part 1: evaluable lesion (including skin or bone lesion only)
    • Part 2: measurable lesion per RECIST v1.1
  • Prior systemic Treatment

    • Part 1: HR-positive/HER2-negative BC

      • At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator
      • At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease
      • HR-positive/HER2-positive BC (Parts 1A/1D): at least 1 prior treatment of approved HER2 targeting therapy
      • Tumors other than BC (Parts 1A/1D): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available
    • Part 2B: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic BC
    • Part 2C:

      • Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or
      • Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal
      • One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy

General Inclusion Criteria

  • All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
  • Adequate renal, liver, and bone marrow function

Exclusion Criteria:

  • Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal
  • Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor
  • Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway
  • Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease
  • Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ
  • Major surgery or radiation within 4 weeks prior to study intervention
  • Last anti-cancer treatment within 2 weeks prior to study intervention
  • Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry
  • Pregnant or breastfeeding female participant
  • Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04557449


Contacts
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Contact: Pfizer CT.gov Call Center 1-800-718-1021 ClinicalTrials.gov_Inquiries@pfizer.com

Locations
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United States, Connecticut
Smilow Cancer Hospital at Yale - New Haven Recruiting
New Haven, Connecticut, United States, 06510
Smilow Cancer Hospital Phase 1 Unit Recruiting
New Haven, Connecticut, United States, 06511
United States, Massachusetts
Brigham & Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Dana-Farber Cancer Institute (DFCI) Recruiting
Boston, Massachusetts, United States, 02215
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
United States, Michigan
START Midwest Recruiting
Grand Rapids, Michigan, United States, 49546
United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT04557449    
Other Study ID Numbers: C4391001
2020-002938-33 ( EudraCT Number )
First Posted: September 21, 2020    Key Record Dates
Last Update Posted: January 31, 2022
Last Verified: January 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Liposarcoma
Adenocarcinoma of Lung
Neoplasms by Site
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Breast Diseases
Skin Diseases
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Sarcoma
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Letrozole
Fulvestrant
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Estrogen Receptor Antagonists