Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (CDK4i)

Pfizer

Status and phase: Active, not recruiting; Phase 2

Conditions: Breast Neoplasms; Adenocarcinoma of Lung; Prostate Cancer; Liposarcoma

Treatments: Drug: Midazolam; Combination Product: Letrozole; Combination Product: Enzalutamide; Combination Product: Fulvestrant; Drug: PF-07220060

Study type: Interventional

Funder types: Industry

Identifiers

NCT04557449

C4391001

2024-512120-11-00 (Registry Identifier)

Details and patient eligibility

About

This is a Phase 1/2A, 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.

The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide.

In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion 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 In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A.

Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC.

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

Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide.

Part 2E is an expansion cohort to evaluate PF-07220060 Monotherapy versus PF-07220060 plus fulvestrant combination therapy. The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants.

The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.

Enrollment: 362 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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/Part1E also include: Refractory HR-positive/HER2-positive BC

• Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests

• Part 1F: prostate cancer

• Part 2A, 2B, 2C and 2E:

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

• Part 1D: metastatic castration resistant prostate cancer

• Lesion:

  • Part 1: evaluable lesion (including skin or bone lesion only)
  • Part 2A, 2B, 2C and 2E: measurable lesion per RECIST v1.1
  • Part 2D: Participants with evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded.

• 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/1E): at least 1 prior treatment of approved HER2 targeting therapy
    • Tumors other than BC (Parts 1A/1D/1E/1F): 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 2A and 2E: participants must have received at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed

  • 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

  • Part 2D:

    • Received prior abiraterone; enzalutamide and CDK4i naive
    • 0-1 line of chemotherapy is allowed 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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362 participants in 17 patient groups

1A Monotherapy Escalation Arm 1

Experimental group

Description:

PF-07220060 Monotherapy Escalation

Treatment:

Drug: PF-07220060

1A Monotherapy Escalation Arm 2

Experimental group

Description:

PF-07220060 Monotherapy Escalation

Treatment:

Drug: PF-07220060

1A Monotherapy Escalation Arm 3

Experimental group

Description:

PF-07220060 Monotherapy Escalation

Treatment:

Drug: PF-07220060

1A Monotherapy Escalation Arm 4

Experimental group

Description:

PF-07220060 Monotherapy Escalation

Treatment:

Drug: PF-07220060

1B Combination Dose Finding Arm 1

Experimental group

Description:

PF-07220060 with Letrozole combination Escalation

Treatment:

Drug: PF-07220060

Combination Product: Letrozole

1B Combination Dose Finding Arm 2

Experimental group

Description:

PF-07220060 with Letrozole Combination Escalation

Treatment:

Drug: PF-07220060

Combination Product: Letrozole

1C Combination Dose Finding Arm 1

Experimental group

Description:

PF-07220060 with Fulvestrant Combination Escalation

Treatment:

Drug: PF-07220060

Combination Product: Fulvestrant

1C Combination Dose Finding Arm 2

Experimental group

Description:

PF-07220060 with Fulvestrant Combination Escalation

Treatment:

Drug: PF-07220060

Combination Product: Fulvestrant

2B Combination Dose Expansion

Experimental group

Description:

PF-07220060 with Letrozole Combination Expansion

Treatment:

Drug: PF-07220060

Combination Product: Letrozole

2C Combination Dose Expansion

Experimental group

Description:

PF-07220060 with fulvestrant Combination Expansion

Treatment:

Drug: PF-07220060

Combination Product: Fulvestrant

1D Monotherapy Food Effect

Experimental group

Description:

PF-07220060 Monotherapy Food Effect

Treatment:

Drug: PF-07220060

1A Monotherapy Escalation Arm 5

Experimental group

Description:

PF-07220060 Monotherapy Escalation

Treatment:

Drug: PF-07220060

1F Combination Dose Finding

Experimental group

Description:

PF-07220060 with Enzalutamide Escalation

Treatment:

Drug: PF-07220060

Combination Product: Enzalutamide

1E DDI Cohort

Experimental group

Description:

PF-07220060 DDI with Midazolam

Treatment:

Drug: PF-07220060

Drug: Midazolam

2D Combination Dose Expansion

Experimental group

Description:

PF-07220060 with enzalutamide Combination Expansion

Treatment:

Drug: PF-07220060

Combination Product: Enzalutamide

2A Combination Dose Expansion

Experimental group

Description:

PF-07220060 with fulvestrant combination dose expansion

Treatment:

Drug: PF-07220060

Combination Product: Fulvestrant

2E Combination Dose Expansion

Experimental group

Description:

PF-07220060 Monotherapy OR PF-07220060 plus fulvestrant combination therapy

Treatment:

Drug: PF-07220060

Combination Product: Fulvestrant