PF-07220060: Pfizer's Next generation CDK4 inhibitor

Pfizer's PF-07220060

PF-07220060 is a novel, potent oral CDK4-selective inhibitor with significant sparing of CDK6. According to the results presented at ASCO 2023, at data cutoff (November 1, 2022), around 34 pts with advanced solid tumors received PF-07220060 in monotherapy dose escalation (Part 1A: 100–500 mg BID), and 26 pts with HR+/HER2- mBC in combination (300mg/400mg BID) with letrozole or fulvestrant (Parts 1B + 1C). The safety results are described on the basis of Part 1A, Part 1B and C, that are been explained below

PART 1A: Advanced solid tumors

  • All patients in the PF-07220060 monotherapy BID cohort had treatment-emergent adverse events (TEAEs). Apparently, across all dose levels the grade 3 TEAEs were neutropenia (14.7%), anemia (8.8%), diarrhea (5.9%), leukopenia (5.9%), and nausea (2.9%)
  • No Grade 4 TEAEs occurred
  • Serious adverse events (SAEs) of any casualty occurred in 11 patients, with COVID-19 accounting for 2 cases, and the remaining SAEs reported in 1 patient each
  • Dose-limiting toxicities occurred with PF-07220060 monotherapy at 500 mg BID

PART 1B and 1C: HR+/HER2- mBC

  • Around 25 (96.2%) patients had TEAEs
  • The grade 3 TEAEs with PF-07220060 BID + ET were neutropenia (15.4%), and nausea (3.8%)
  • SAEs occurred in 4 (15.4%) patients, all in part 1C
  • Dose-limiting toxicities occurred with PF-07220060 400 mg BID + fulvestrant

In terms of efficacy findings, the below mentioned table explains each parameter.

Best overall response based on investigator assessment 

n (%)

Part 1A



Part 1B and 1C

(combination with ET)a


Complete response (CR)


1 (4.8)

Partial response (PR)


5 (23.8)

Stable disease 

18 (62.1)

12 (57.1)

Disease control rate

22 (75.9)

18 (85.7)

Clinical benefit response

10 (34.5)

11 (52.4)

Objective response (CR + PR)


6 (28.6)

Median PFS, weeks (95% CI)

23.9 (15.7, 46.4)

24.7 (23.1, 47.4)

a: patients with prior CDK4/6i

CI- confidence interval, mBC- metastatic breast cancer, PFS- progression free survival 


KOL insights 

“A 21-patient hormone therapy combo arm fared better, with one complete response and five partial responses.” –Expert Opinion.

“Next generation CDK4-selective inhibitor PF-07220060 shows promising activity and great tox profile in a heavily pretreated (100% post cdk4/6) HR+HER2- #bcsm population. ORR 28.6% mPFS 24.7 months.”- Expert Opinion.

“Pfizer also has a CDK4 selective inhibitor in development, PF-07220060, although it doesn’t seem to have much single-agent activity”-Expert Opinion.


According to the statistics from Surveillance, Epidemiology, and End Results (SEER), more than 200,000 cases of breast cancer are diagnosed every year among the female population in the US. The prognosis of invasive breast cancer is strongly influenced by the stage of the disease—that is, the extent or spread of the cancer when it is first diagnosed. Based on the above findings, it is clear that the combination of PF-07220060 and ET delivered promising results in HR+/HER2-mBC patients. Moreover, PF-07220060 demonstrated impressive tolerability alone and in synergy with endocrine therapy. Apart from that, Pfizer is moving forward with PF-07220060, initiating expansion cohorts targeting both resistant and CDK4/6-naive patients. This strategic move aligns with the growing understanding of CDK4's paramount significance in breast cancer, surpassing the role of CDK6. Lastly, the dose expansion study with PF-07220060 + ET in patients with HR+/HER2- mBC post CDK4/6i and in CDK4/6i naive patients is ongoing. 

Among the approved therapies, CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) have attracted the most attention. CDK4/6 regulate cell cycle progression through their reversible interaction with cyclin D1. Approximately 29 and 14% of patients with HR+/HER2− BC were found to have amplification of cyclin D1 and CDK4, respectively.

Get a more detailed overview of the key developments in the domain at: ER+/ HER2 -ve Breast Cancer Market, HER2-Positive Breast Cancer Market, ESR1 Mutated Metastatic Breast Cancer Market, ESR1-Mutated Metastatic Breast Cancer Pipeline Insight, Triple Negative Breast Cancer (TNBC) Market, Triple Negative Breast Cancer (TNBC) Pipeline Insight, Metastatic triple-negative breast cancer (mTNBC) Market, Metastatic Triple-Negative Breast Cancer (mTNBC) Pipeline Insight