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

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

Sponsors

Lead Sponsor: Pfizer

Source 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). Part 1B and Part 1C may be enrolled and conducted in parallel at the completion of Part 1A.

Overall Status Not yet recruiting
Start Date October 1, 2020
Completion Date September 4, 2024
Primary Completion Date September 4, 2024
Phase Phase 1
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of participants with dose limiting toxicities in the Dose Escalation Portion Baseline up to day 28 of Cycle 1.
Incidence of clinically significant AEs Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days
Incidence of clinically significant laboratory assessments Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months
Incidence of clinically significant abnormal vital and ECG parameters 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)
Secondary Outcome
Measure Time Frame
Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
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 Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
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: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Tumor Response observed in participants in Dose Escalation and Dose Finding portion baseline up to approximately 24 months
Duration of Response (DOR) in participants enrolled in the Dose Escalation and Dose Finding portion baseline up to approximately 24 months
Progression Free Survival (PFS) observed in participants in the Dose Escalation and Dose Finding portion baseline up to approximately 24 months
Time to Progression (TTP) observed in participants enrolled in the Dose Escalation and Dose Finding portion baseline up to approximately 24 months
Overall Survival observed in participants enrolled in the Dose Expansion Arms baseline up to approximately 24 months
Enrollment 52
Condition
Intervention

Intervention Type: Drug

Intervention Name: PF-07220060

Description: CDK4 inhibitor

Intervention Type: Combination Product

Intervention Name: Letrozole

Description: Endocrine Therapy

Other Name: Femara

Intervention Type: Combination Product

Intervention Name: Fulvestrant

Description: Endocrine Therapy

Other Name: Faslodex

Eligibility

Criteria:

Inclusion Criteria - Disease Characteristics - Breast Cancer (Part 1A, Part 1B and Part 1C) - Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) breast cancer (2L + with prior CDK 4/6) locally advance or metastatic breast cancer. Participants should have received at least 1 line of SOC, including CDK4/6 inhibitor therapy, or at least 1 line of anti-endocrine therapy in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease - Part 1A only: Refractory HR-positive (HR+), Human Epidermal Growth Factor Receptor 2 Positive (HER2+) breast cancer - Evaluable lesion (including skin or bone lesion only) - Disease Characteristics - Part 1A: Tumors other than BC - Participants with advanced or metastatic disease - Participants with histological or cytological diagnosis of adenocarcinoma of NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests, that is resistant to at least 2 lines of standard systemic therapy for advanced or recurrent disease or for which no standard therapy is available - Participants must not be eligible to undergo therapy with curative intent (surgery or radiation therapy with or without chemotherapy 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: - 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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Pfizer CT.gov Call Center Study Director Pfizer
Overall Contact

Last Name: Pfizer CT.gov Call Center

Phone: 1-800-718-1021

Email: [email protected]

Location
Facility: The University of Texas - MD Anderson Cancer Center
Location Countries

United States

Verification Date

September 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 8
Arm Group

Label: Monotherapy Escalation Arm 1

Type: Experimental

Description: PF-07220060 Monotherapy Escalation

Label: Monotherapy Escalation Arm 2

Type: Experimental

Description: PF-07220060 Monotherapy Escalation

Label: Monotherapy Escalation Arm 3

Type: Experimental

Description: PF-07220060 Monotherapy Escalation

Label: Monotherapy Escalation Arm 4

Type: Experimental

Description: PF-07220060 Monotherapy Escalation

Label: 1B Combination Dose Finding Arm 1

Type: Experimental

Description: PF-07220060 with Letrozole combination Escalation

Label: 1B Combination Dose Finding Arm 2

Type: Experimental

Description: PF-07220060 with Letrozole Combination Escalation

Label: 1C Combination Dose Finding Arm 1

Type: Experimental

Description: PF-07220060 with Fulvestrant Combination Escalation

Label: 1C Combination Dose Finding Arm 2

Type: Experimental

Description: PF-07220060 with Fulvestrant Combination Escalation

Acronym CDK4
Patient Data No
Study Design Info

Allocation: Non-Randomized

Intervention Model: Sequential Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov