Study of PF-07224826, as a Single Agent or in Combination With Endocrine Therapy in Participants With Breast Cancer and Other Advanced Solid Tumors.

Pfizer

Status and phase: Withdrawn; Phase 1

Conditions: Endometrial; Non-small Cell Lung Cancer (NSCLC); Breast Cancer; Solid Tumors; Ovarian Cancer; Liposarcoma

Treatments: Combination Product: Fulvestrant; Drug: PF-07224826

Study type: Interventional

Funder types: Industry

Identifiers

NCT05905341

C5331001

Details and patient eligibility

About

This is a Phase 1, open-label, multicenter, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of PF-07224826, as a single agent or in combination with endocrine therapy in participants with advanced solid tumors. This study will be divided into dose escalation/finding (Part 1) and dose expansion (Part 2).

In Part 1, participants with locally recurrent/advanced or metastatic Triple Negative Breast Cancer (TNBC), platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy.

In Part 2 (Arm A), PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative advanced or mBC participants who have received prior CDK4/6 inhibitor. In Part 2 (Arm B), PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative locally advanced or mBC participants whose disease has progressed on prior endocrine therapy and is naïve to CDK4/6 inhibitors.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Part 1:

  • Participants with HR-positive HER2-negative locally advanced or metastatic breast cancer.
  • Participants with locally recurrent/advanced or metastatic TNBC.
  • Participants with advanced platinum resistant epithelial ovarian cancer (EOC)/fallopian tube cancer/primary peritoneal cancer (PPC).
  • Other advanced solid tumor types: Tumors other than BC or Ovarian: NSCLC, prostate, endometrial, liposarcoma, or other tumors with cyclin D (CCND) and cyclin E (CCNE) implicated in pathogenesis either by gene amplification or overexpression.

• Part 2 (Arm A): Participants with HR positive HER2 negative locally advanced or mBC (post CDK4/6 inhibitors).

• Part 2 (Arm B): Participants with HR positive HER2 negative locally advanced or mBC (naïve to CDK4/6 inhibitors).

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1.

• Adequate Bone Marrow Function

Exclusion criteria

• Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease as indicated by clinical symptoms, Cerebral edema, and/or progressive growth. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated (eg, radiotherapy, stereotactic surgery) and are clinically stable off anticonvulsants and steroids for at least 4 weeks before enrollment and have no evidence of progression at time of study enrollment.
• Participants with advanced/metastatic, symptomatic, visceral spread, that are at risk of life-threatening complications in the short term (eg, including participants with massive uncontrolled effusions [pleural, pericardial, peritoneal], pulmonary lymphangitis, and over 50% liver involvement).
• 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.
• Last anticancer treatment within 2 weeks (or 5 half-lives, whichever is shorter), unless the last immediate anticancer treatment contained an antibody-based agent(s) (approved or investigational), then the interval of 4 weeks or 5 half-lives (whichever is shorter) is required prior to receiving the study intervention.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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0 participants in 7 patient groups

Part 1 Dose Escalation-Dose Level 1

Experimental group

Description:

In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 2

Experimental group

Description:

In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 3

Experimental group

Description:

In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 4

Experimental group

Description:

In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 1 Dose Escalation-Dose Level 5

Experimental group

Description:

In Part 1, participants with locally recurrent/advanced or metastatic TNBC, platinum resistant ovarian cancer and other advanced solid tumors will receive PF-07224826 as a single agent. Participants with HR-positive HER2-negative advanced or mBC will receive PF-07224826 in combination with endocrine therapy. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 2 - Arm A

Experimental group

Description:

In Part 2 Arm A, PF-07224826 will be evaluated in combination with fulvestrant in HR positive HER2 negative advanced or mBC participants who have received prior CDK4/6 inhibitor. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Part 2 - Arm B

Experimental group

Description:

In Part 2 Arm B, PF-07224826 will be evaluated in combination with fulvestrant in HR-positive HER2-negative locally advanced or mBC participants whose disease has progressed on prior endocrine therapy and is naïve to CDK4/6 inhibitors. PF-07224826 will be administered orally, once daily, on a continuous basis.

Treatment:

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Drug: PF-07224826

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant

Combination Product: Fulvestrant