Sponsor: Pfizer (industry)
Phase: 3
Start date: Jan. 6, 2025
Planned enrollment: 1020
PF-07220060, also known as atirmociclib, is an investigational, orally bioavailable, highly selective cyclin-dependent kinase 4 (CDK4) inhibitor developed by Pfizer. It is being evaluated for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer (mBC), particularly in patients who have progressed after prior CDK4/6 inhibitor and endocrine therapy.
PF-07220060 selectively inhibits CDK4, a serine/threonine kinase that plays a crucial role in cell cycle progression from the G1 phase to the S phase. By inhibiting CDK4, PF-07220060 prevents the phosphorylation of the retinoblastoma protein (Rb), leading to cell cycle arrest and suppression of tumor cell proliferation. Notably, PF-07220060 exhibits significant sparing of CDK6, potentially reducing associated toxicities compared to non-selective CDK4/6 inhibitors. (mycancergenome.org)
In a Phase 1/2a study involving patients with HR+/HER2− mBC who had progressed on prior CDK4/6 inhibitors and endocrine therapy, PF-07220060 demonstrated promising efficacy. Among patients with measurable disease (n=21), the study reported:
Additionally, 30.8% of patients continued treatment without progression for up to 60 weeks. (ascopubs.org)
PF-07220060, both as monotherapy and in combination with endocrine therapy, was generally well tolerated. Common treatment-emergent adverse events (TEAEs) included:
No Grade 4 or higher TEAEs were reported. The incidence of Grade 3 neutropenia and other TEAEs was low, enabling high relative dose intensity and continuous target coverage. (ascopubs.org)
Last updated: Apr 2025
As of August 3, 2025, the FOURLIGHT-3 trial (NCT06760637) is actively recruiting participants. This Phase 3 study, initiated by Pfizer, aims to evaluate the safety and efficacy of PF-07220060 in combination with letrozole compared to standard CDK4/6 inhibitors plus letrozole in adults with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer who have not received prior systemic treatment for advanced disease. (ichgcp.net)
The trial commenced on January 6, 2025, and is expected to continue until January 2, 2029. As of the latest update on June 17, 2025, no interim results or analyses have been published. Consequently, there is currently no publicly available information regarding the trial's outcomes or its potential impact on breast cancer treatment. (fdaaa.trialstracker.net)
For oncologists and patients considering participation, it's important to note that the trial is ongoing, and detailed results will be available upon its completion. Interested individuals should consult with healthcare providers or contact the study coordinators for the most current information.
Key References:
Last updated: Aug 2025
Goal: To compare the safety and efficacy of PF-07220060 plus letrozole versus standard-of-care CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus letrozole as first-line therapy for patients with HR-positive, HER2-negative, locally advanced or metastatic breast cancer.
Patients: Adults (over 18 years) with histologically confirmed HR-positive, HER2-negative, locally advanced or metastatic breast cancer, with no prior systemic treatment for advanced/metastatic disease. Patients must have measurable or non-measurable bone-only disease per RECIST 1.1. Patients with visceral crisis, CNS metastases, or inadequate organ function are excluded.
Design: Interventional, open-label, randomized, multicenter phase 3 trial with two arms comparing PF-07220060 plus letrozole to investigator's choice of CDK4/6 inhibitor plus letrozole. Allocation is randomized.
Treatments: The investigational arm receives PF-07220060, an oral CDK4-selective inhibitor, in combination with letrozole. PF-07220060 is designed to selectively block CDK4 while sparing CDK6, potentially reducing hematologic toxicity such as neutropenia and allowing for greater drug exposure compared with dual CDK4/6 inhibitors. Early-phase studies of PF-07220060 in pretreated HR+/HER2- breast cancer have shown a 32% objective response rate and a median progression-free survival of 8.1 months, with a favorable safety profile and high relative dose intensity. The comparator arm receives oral letrozole with the investigator's choice of palbociclib, ribociclib, or abemaciclib, which are standard CDK4/6 inhibitors approved in the first-line setting for HR+/HER2- advanced breast cancer.
Outcomes: The primary endpoint is progression-free survival (PFS) by blinded independent central review per RECIST 1.1. Key secondary endpoints include overall survival, investigator-assessed PFS, objective response rates, duration of response, safety and tolerability (incidence and severity of adverse events and serious adverse events), patient-reported quality of life (EORTC QLQ C30, EQ-5D-5L, BPI-SF, EORTC BR42), and mean change from baseline in circulating tumor DNA (ctDNA).
Burden on patient: Burden on participants is expected to be low to moderate, similar to other phase 3 registration trials for advanced breast cancer using oral agents. Patients will have regular study visits for clinical assessments, laboratory tests, and imaging (scans every 8 weeks initially, then every 12 weeks), consistent with standard-of-care monitoring. Quality of life questionnaires and ctDNA blood sampling may be performed periodically, but there is no mention of protocol-mandated tumor biopsies or frequent pharmacokinetic sampling, limiting additional burden. Both treatment arms use oral agents, minimizing infusion visits.
Inclusion Criteria:
* Histological confirmation of breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
* Documented estrogen receptor (ER) and/or progesterone receptor (PR)-positive tumor
* Documented HER2-negative tumor
* Previously untreated with any systemic anticancer therapy for their locally advanced or metastatic disease.
* Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1
Exclusion Criteria:
* In visceral crisis at risk of immediately life-threatening complications in the short term.
* Current or past history of central nervous system metastases.
* Have received prior (neo)adjuvant endocrine therapy (ET) and had recurrence during or within 12 months after the last dose of ET.
* Have received prior (neo)adjuvant CDK4/6i and had recurrence during or within 12 months after the last dose of CDK4/6i.
* Inadequate renal function, hepatic dysfunction, or hematologic abnormalities.
Woolloongabba, Queensland, 4102, Australia
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Douglas, Queensland, 4814, Australia
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Capel Sound, Victoria, 3940, Australia
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Parkville, Victoria, 3052, Australia
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Frankston, Victoria, 3199, Australia
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Melbourne, Victoria, 3000, Australia
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Gilly, Hainaut, 6060, Belgium
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Gent, Oost-vlaanderen, 9000, Belgium
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Leuven, Vlaams-brabant, 3000, Belgium
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Aalst, 9300, Belgium
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Sofia, Sofia (stolitsa), 1632, Bulgaria
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Shumen, 9700, Bulgaria
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Sofia, 1330, Bulgaria
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Plovdiv, 4004, Bulgaria
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Haskovo, 6300, Bulgaria
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Gabrovo, 5300, Bulgaria
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Burgas, 8000, Bulgaria
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Fredericton, New Brunswick, E3B 5N5, Canada
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Toronto, Ontario, M5G 2M9, Canada
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Beijing, Beijing, 100021, China
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Beijing, Beijing, 100142, China
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Beijing, Beijing, 100034, China
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Foshan, Guangdong, 528000, China
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Guangzhou, Guangdong, 510060, China
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Wuhan, Hubei, 430030, China
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Changsha, Hunan, 410013, China
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Nanjing, Jiangsu, 210031, China
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Changchun, Jilin, 130021, China
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Dalian, Liaoning, 116023, China
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Shenyang, Liaoning, 110015, China
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Xi'an, Shaanxi, 710061, China
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Linhai, Zhejiang, 317000, China
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Hangzhou, Zhejiang, 310016, China
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Prague, Praha 4, 14059, Czechia
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Praha, Praha 5, 150 06, Czechia
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Nový Jičín, 741 01, Czechia
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Copenhagen, Hovedstaden, 2100, Denmark
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Aarhus, Midtjylland, 8200, Denmark
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Aalborg, Nordjylland, 9000, Denmark
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Esbjerg, Syddanmark, 6700, Denmark
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Soenderborg, Syddanmark, 6400, Denmark
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Tampere, Pirkanmaa, 33520, Finland
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Vaasa, Pohjanmaa, 65130, Finland
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Helsinki, Uusimaa, 00029, Finland
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Turku, Varsinais-suomi, 20520, Finland
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Bordeaux, Aquitaine, 33076, France
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Créteil, Île-de-france, 94000, France
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Rennes, Ille-et-vilaine, 35042, France
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Montpellier, Languedoc-roussillon, 34070, France
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Saint Herblain, Loire-atlantique, 44805, France
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ANGERS cedex 02, Maine-et-loire, 49055, France
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Rouen, Seine-maritime, 76038, France
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La Roche-sur-Yon, Vendée, 85000, France
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Bayonne, 64109, France
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Koblenz, Rheinland-pfalz, 56068, Germany
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Dresden, Sachsen, 01307, Germany
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Dresden, 01307, Germany
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Hamburg, 20249, Germany
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Athens, Attikí, 115 22, Greece
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Marousi, Attikí, 151 23, Greece
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Αθήνα, Attikí, 115 28, Greece
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Athens, 115 28, Greece
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Eger, Heves, 3300, Hungary
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Budapest, 1122, Hungary
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New Delhi, Delhi, 110085, India
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Surat, Gujarat, 395002, India
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Gurugram, Haryana, 122001, India
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Bangalore, Karnataka, 560069, India
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Pune, Maharashtra, 411004, India
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Thane, Maharashtra, 401107, India
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Pune, Maharashtra, 411004, India
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Nashik, Maharashtra, 422009, India
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Mumbai, Maharashtra, 400012, India
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Hyderabad, Telangana, 500034, India
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Kolkata, WEST Bengal, 700054, India
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Dublin, D07 WKW8, Ireland
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Dublin, D07 A8NN, Ireland
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Dublin, D9, Ireland
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Petah Tikva, Hamerkaz, 4941492, Israel
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Ramat Gan, Hamerkaz, 5265601, Israel
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Haifa, Hatsafon, 3109601, Israel
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Tel Aviv, Tell Abīb, 6423906, Israel
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Jerusalem, Yerushalayim, 9112001, Israel
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Meldola, Emilia-romagna, 47014, Italy
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Aviano, Friuli-venezia Giulia, 33081, Italy
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Rome, Roma, 00144, Italy
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Firenze, Toscana, 50134, Italy
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Novara, 28100, Italy
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Milano, 20141, Italy
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Nagoya, Aichi, 464-8681, Japan
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Nagoya, Aichi, 466-8560, Japan
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Nagoya, Aichi, 467-8602, Japan
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Otashi, Gunma, 373-8550, Japan
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Sapporo, Hokkaido, 003-0804, Japan
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Yokohama, Kanagawa, 2418515, Japan
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Sakyo-ku, Kyoto, 606-8507, Japan
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Sendai, Miyagi, 980-8574, Japan
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Suita, Osaka, 565-0871, Japan
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Bunkyo-ku, Tokyo, 113-8431, Japan
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Chuo-ku, Tokyo, 104-0045, Japan
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Koto-ku, Tokyo, 135-8550, Japan
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Shinagawa, Tokyo, 142-8666, Japan
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Shinjuku City, Tokyo, 162-8655, Japan
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Kumamoto, 862-8655, Japan
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Chiba, 260-8717, Japan
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Fukuoka, 811-1395, Japan
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Hiroshima, 730-8518, Japan
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Okayama, 700-8558, Japan
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Osaka, 540-0006, Japan
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Osaka, 541-8567, Japan
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Incheon, Incheon-gwangyeoksi [incheon], 21565, Korea, Republic of
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Gangnam-gu, Seoul-teukbyeolsi [seoul], 06273, Korea, Republic of
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Seoul, Seoul-teukbyeolsi [seoul], 02841, Korea, Republic of
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Seoul, Seoul-teukbyeolsi [seoul], 05505, Korea, Republic of
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Seoul, Seoul-teukbyeolsi [seoul], 07985, Korea, Republic of
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Łódź, Łódzkie, 91-614, Poland
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Kraków, Małopolskie, 30-348, Poland
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Kraków, Małopolskie, 30-727, Poland
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Skórzewo, Wielkopolskie, 60-185, Poland
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Otwock, 05-400, Poland
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Michalovce, Košický KRAJ, 071 01, Slovakia
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Komarno, Nitriansky KRAJ, 945 05, Slovakia
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Banka, Trnavský KRAJ, 921 01, Slovakia
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Elche, Alicante, 03203, Spain
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Barcelona, Barcelona [barcelona], 08035, Spain
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Hospitalet, Barcelona [barcelona], 08907, Spain
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Jerez de la Frontera, Cádiz, 11407, Spain
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Barcelona, Catalunya [cataluña], 08036, Spain
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Madrid, Madrid, Comunidad DE, 28041, Spain
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Malaga, Málaga, 29010, Spain
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Bilbo, PAÍS Vasco, 48013, Spain
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Madrid, 28050, Spain
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Granada, 18016, Spain
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Salamanca, 37007, Spain
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Sevilla, 41009, Spain
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Gävle, Gävleborgs LÄN [se-21], 80187, Sweden
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Stockholm, Stockholms LÄN [se-01], 11883, Sweden
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Uppsala, Uppsala LÄN [se-03], 751 85, Sweden
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Västerås, Västmanlands LÄN [se-19], 721 89, Sweden
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Gothenburg, Västra Götalands LÄN [se-14], 413 45, Sweden
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Sundsvall, 856 40, Sweden
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Jönköping, 553 05, Sweden
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Stockholm, 112 19, Sweden
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Aarau, Aargau, 5000, Switzerland
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Bern, Berne, 3010, Switzerland
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Frauenfeld, Thurgau, 8500, Switzerland
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Olten, 4600, Switzerland
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Münsterlingen, 8596, Switzerland
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Chur, 7000, Switzerland
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Baden, 5404, Switzerland
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Winterthur, 8401, Switzerland
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Zhu Bei City, Hsinchu, 302, Taiwan
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Taoyuan, 333, Taiwan
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Taipei, 112, Taiwan
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Taipei, 11217, Taiwan
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Taipei, 10449, Taiwan
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Taipei, 10002, Taiwan
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Taichung, 407, Taiwan
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Tainan, 704, Taiwan
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Istanbul, İ̇stanbul, 34722, Turkey
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Istanbul, İ̇stanbul, 34214, Turkey
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Istanbul, İ̇stanbul, 34295, Turkey
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Ankara, 06520, Turkey
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Sakarya, 54290, Turkey
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Diyarbakir, 21200, Turkey
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Ankara, 06560, Turkey
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Ankara, 06230, Turkey
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Ankara, 06010, Turkey
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London, Hammersmith AND Fulham, W6 8RF, United Kingdom
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London, London, CITY OF, w1g 6ad, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Glendale, Arizona, 85306, United States
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Status: Recruiting
Mesa, Arizona, 85202, United States
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Mesa, Arizona, 85206, United States
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Scottsdale, Arizona, 85260, United States
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Phoenix, Arizona, 85028, United States
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Chandler, Arizona, 85224, United States
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Gilbert, Arizona, 85297, United States
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Rogers, Arkansas, 72758, United States
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Status: Recruiting
Fayetteville, Arkansas, 72703, United States
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Springdale, Arkansas, 72762, United States
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Status: Recruiting
Pasadena, California, 91105, United States
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Status: Recruiting
Los Alamitos, California, 90720, United States
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Status: Recruiting
Los Angeles, California, 90033, United States
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Status: Recruiting
Los Angeles, California, 90033, United States
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Status: Recruiting
Los Angeles, California, 90033, United States
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Status: Recruiting
Los Angeles, California, 90033, United States
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Status: Recruiting
Newport Beach, California, 92663, United States
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Status: Recruiting
Newport Beach, California, 92663, United States
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Status: Recruiting
West Hills, California, 91307, United States
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Status: Not yet recruiting
Grand Junction, Colorado, 81501, United States
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Status: Recruiting
Denver, Colorado, 80218, United States
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Status: Recruiting
Denver, Colorado, 80218, United States
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Status: Recruiting
Golden, Colorado, 80401, United States
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Status: Recruiting
Golden, Colorado, 80401, United States
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Status: Recruiting
Grand Junction, Colorado, 81501, United States
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Status: Recruiting
Grand Junction, Colorado, 81505, United States
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Status: Recruiting
Washington, District of Columbia, 20010, United States
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Status: Recruiting
Orlando, Florida, 32804, United States
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Status: Recruiting
Altamonte Springs, Florida, 32701, United States
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Status: Recruiting
Altamonte Springs, Florida, 32701, United States
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Status: Recruiting
Altamonte Springs, Florida, 32701, United States
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Status: Recruiting
Aventura, Florida, 33180, United States
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Status: Recruiting
Boca Raton, Florida, 33486, United States
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Status: Not yet recruiting
Miami Beach, Florida, 33140, United States
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Status: Recruiting
Miami Beach, Florida, 33140, United States
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Status: Recruiting
Orange City, Florida, 32763, United States
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Status: Recruiting
Orlando, Florida, 32803, United States
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Status: Recruiting
Orlando, Florida, 32804, United States
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Status: Recruiting
Savannah, Georgia, 31405, United States
No email / No phone
Status: Recruiting
Meridian, Idaho, 83642, United States
No email / No phone
Status: Recruiting
Boise, Idaho, 83712, United States
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Status: Recruiting
Boise, Idaho, 83712, United States
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Status: Recruiting
Fruitland, Idaho, 83619, United States
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Status: Recruiting
Meridian, Idaho, 83642, United States
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Status: Recruiting
Nampa, Idaho, 83687, United States
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Status: Recruiting
Skokie, Illinois, 60077, United States
No email / No phone
Status: Recruiting
Elmhurst, Illinois, 60126, United States
No email / No phone
Status: Recruiting
Evanston, Illinois, 60202, United States
No email / No phone
Status: Recruiting
Hinsdale, Illinois, 60521, United States
No email / No phone
Status: Not yet recruiting
Naperville, Illinois, 60540, United States
No email / No phone
Status: Recruiting
New Lenox, Illinois, 60451, United States
No email / No phone
Status: Not yet recruiting
Skokie, Illinois, 60077, United States
No email / No phone
Status: Recruiting
Annapolis, Maryland, 21401, United States
No email / No phone
Status: Recruiting
Baltimore, Maryland, 21202, United States
No email / No phone
Status: Recruiting
Boston, Massachusetts, 02115, United States
No email / No phone
Status: Not yet recruiting
Boston, Massachusetts, 02215, United States
No email / No phone
Status: Not yet recruiting
Boston, Massachusetts, 02215, United States
No email / No phone
Status: Not yet recruiting
Newton, Massachusetts, 02459, United States
No email / No phone
Status: Not yet recruiting
Saint Paul, Minnesota, 55102, United States
No email / No phone
Status: Recruiting
Coon Rapids, Minnesota, 55433, United States
No email / No phone
Status: Recruiting
Minneapolis, Minnesota, 55407, United States
No email / No phone
Status: Recruiting
Kansas City, Missouri, 64111, United States
No email / No phone
Status: Recruiting
Bozeman, Montana, 59715, United States
No email / No phone
Status: Recruiting
Reno, Nevada, 89502, United States
No email / No phone
Status: Recruiting
Reno, Nevada, 89502, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97225, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97213, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97213, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97213, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97225, United States
No email / No phone
Status: Recruiting
Portland, Oregon, 97225, United States
No email / No phone
Status: Recruiting
Tyler, Texas, 75701, United States
No email / No phone
Status: Recruiting
Tyler, Texas, 75708, United States
No email / No phone
Status: Recruiting
Salt Lake City, Utah, 84106, United States
No email / No phone
Status: Not yet recruiting
Bountiful, Utah, 84010, United States
No email / No phone
Status: Not yet recruiting
Layton, Utah, 84041, United States
No email / No phone
Status: Not yet recruiting
Murray, Utah, 84107, United States
No email / No phone
Status: Not yet recruiting
Ogden, Utah, 84405, United States
No email / No phone
Status: Not yet recruiting
Orem, Utah, 84057, United States
No email / No phone
Status: Not yet recruiting
Pleasant Grove, Utah, 84062, United States
No email / No phone
Status: Not yet recruiting
Provo, Utah, 84604, United States
No email / No phone
Status: Not yet recruiting
West Valley City, Utah, 84119, United States
No email / No phone
Status: Not yet recruiting
Salt Lake City, Utah, 84102, United States
No email / No phone
Status: Not yet recruiting
West Jordan, Utah, 84088, United States
No email / No phone
Status: Not yet recruiting