Last reviewed 2026-04-20 · How we verify

PF-06804103 + Palbociclib +Letrozole (pf-06804103-palbociclib-letrozole)

PF-06804103 + Palbociclib +Letrozole (generic name: pf-06804103-palbociclib-letrozole) is a Selective estrogen receptor degrader (SERD) + CDK4/6 inhibitor + aromatase inhibitor combination drug developed by Pfizer Inc.. It is currently in discontinued development.

Triple-agent therapy combining estrogen receptor degradation, CDK4/6 inhibition, and aromatase inhibition to block estrogen signaling and cell-cycle progression in HR+ breast cancer.

PF-06804103 combined with palbociclib and letrozole is a discontinued triple-agent hormonal therapy developed by Pfizer for hormone receptor-positive (HR+), HER2-negative breast cancer. The regimen combines PF-06804103 (a selective estrogen receptor degrader, SERD) with palbociclib (a CDK4/6 inhibitor) and letrozole (an aromatase inhibitor), targeting multiple points in the estrogen signaling pathway to overcome endocrine resistance. The combination was evaluated in Phase 1 dose-escalation studies but was terminated before advancing to later-stage development, suggesting either safety concerns, lack of efficacy signals, or strategic portfolio decisions by Pfizer. This triple-agent approach represented an attempt to improve upon dual-therapy regimens (CDK4/6 inhibitor + endocrine therapy) by adding SERD-mediated estrogen receptor degradation. The discontinuation reflects the competitive landscape in HR+/HER2− breast cancer, where established combinations like palbociclib + letrozole and ribociclib + letrozole already dominate clinical practice. No commercial revenue was generated as the program did not reach regulatory approval.

At a glance

Mechanism of action

This combination therapy targets hormone receptor-positive breast cancer through three complementary mechanisms. PF-06804103 acts as a selective estrogen receptor degrader (SERD), binding to the estrogen receptor and promoting its proteasomal degradation, thereby eliminating both ligand-dependent and ligand-independent signaling. Palbociclib is a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor that blocks the G1/S cell-cycle checkpoint by preventing phosphorylation of the retinoblastoma protein, halting cancer cell proliferation. Letrozole is a non-steroidal aromatase inhibitor that reduces circulating estrogen levels by blocking the conversion of androgens to estrogen in postmenopausal women. Together, these three agents create a multi-layered blockade: letrozole reduces estrogen availability, palbociclib prevents cell-cycle progression even when estrogen signaling occurs, and PF-06804103 degrades any remaining estrogen receptors, theoretically overcoming resistance mechanisms that develop with dual-therapy approaches.

Approved indications

No approved indications tracked.

Pipeline indications

• Hormone receptor-positive, HER2-negative breast cancer — Phase 1

Common side effects

No common side effects on file.

Key clinical trials

• PF-06804103 Dose Escalation in HER2 Positive and Negative (Negative Only in Part 2) Solid Tumors (PHASE1)

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• PF-06804103 + Palbociclib +Letrozole CI brief — competitive landscape report
• PF-06804103 + Palbociclib +Letrozole updates RSS · CI watch RSS
• Pfizer Inc. portfolio CI

Frequently asked questions about PF-06804103 + Palbociclib +Letrozole

Related

• Drug class: All Selective estrogen receptor degrader (SERD) + CDK4/6 inhibitor + aromatase inhibitor combination drugs
• Target: All drugs targeting Estrogen receptor alpha (ERα), CDK4/6, aromatase
• Manufacturer: Pfizer Inc. — full pipeline
• Therapeutic area: All drugs in Oncology
• Compare: PF-06804103 + Palbociclib +Letrozole vs similar drugs
• Pricing: PF-06804103 + Palbociclib +Letrozole cost, discount & access