atirmociclib (PF-07220060) / Pfizer - LARVOL DELTA

C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=320 | Recruiting | Sponsor: Pfizer | Trial completion date: Jan 2028 ➔ Sep 2029

Trial completion date • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • CDKN2A • ER • HER-2

Randomized phase 2 trial of preoperative atirmociclib plus letrozole on Ki-67 tumor expression in HR+/HER2− early breast cancer (ESMO 2025) - No abstract available

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Randomized phase 3 clinical trial evaluating atirmociclib plus letrozole versus a CDK4/6 inhibitor plus letrozole as first-line treatment for patients with HR+/HER2− advanced/metastatic breast cancer (ESMO 2025) - No abstract available

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Long-term safety and efficacy of first-line atirmociclib + letrozole for the treatment of patients with HR+/HER2− metastatic breast cancer (mBC) (ESMO 2025) - No abstract available

Clinical • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2

Synthesis of potent and selective CDK4 inhibitors (ACS-Fall 2025) - "These agents, however, show neutropenia, likely due to the role of CDK6 in hematopoiesis. Herein described is the synthesis of a series of selective CDK4 inhibitors including atirmociclib (PF-07220060) which is currently in a phase 3 clinical trial."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Solid Tumor • CDK6 • HER-2

Discovery of Atirmociclib (PF-07220060), a potent and selective CDK4 inhibitor (ACS-Fall 2025) - "These agents, however, show neutropenia, likely due to the role of CDK6 in hematopoiesis. Herein described is the design and synthesis of a series of selective CDK4 inhibitors including atirmociclib (PF-07220060) which is currently in a phase 3 clinical trial."

Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Solid Tumor • CDK6 • HER-2

A Study to Compare Two Tablet Formulations of Study Medicine Atirmociclib in Healthy Participants (clinicaltrials.gov) - P1 | N=34 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A Study to Learn if the Study Medicine Called Carbamazepine Changes How the Body Processes PF-07220060 (clinicaltrials.gov) - P1 | N=14 | Completed | Sponsor: Pfizer | Not yet recruiting ➔ Completed

Trial completion

C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=320 | Recruiting | Sponsor: Pfizer | N=186 ➔ 320 | Trial completion date: Mar 2027 ➔ Jan 2028 | Trial primary completion date: Aug 2025 ➔ Jan 2028

Enrollment change • Trial completion date • Trial primary completion date • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • CDKN2A • ER • HER-2

Effect of atirmociclib plus endocrine therapy (ET) on serum thymidine kinase activity (TKa) in a phase I study of patients with HR+/HER2− metastatic breast cancer (mBC) (ESMO-BC 2025) - P1 | "Here, we evaluated the effect of atirmociclib + ET on serum TKa and its relationship with progression-free survival (PFS) in pts with prior CDK4/6i use in Parts 1B (300 mg/400 mg atirmociclib BID + letrozole) and 1C (300 mg/400 mg atirmociclib BID + fulvestrant), and treatment-naïve pts in Part 2B (300 mg atirmociclib BID + letrozole). Blood samples were collected at baseline (Cycle 1 Day 1 [C1D1]), C1D15 and C2D1. In this phase I study, atirmociclib + ET achieved strong inhibition of TKa in pts with HR+/HER2− mBC, demonstrating PD effects. Overall, lower baseline TKa was associated with longer PFS. Pts with sustained complete inhibition of TKa tended to have longer PFS, suggesting that deeper CDK4 target modulation by atirmociclib may lead to improved clinical outcomes."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK6 • HER-2

Relay Therapeutics Reports First Quarter 2025 Financial Results and Corporate Updates (GlobeNewswire) - "RLY-2608 Highlights: Breast Cancer (i) Initiation of Phase 3 ReDiscover-2 trial of RLY-2608 + fulvestrant in PI3Kα-mutated, CDK4/6 pre-treated, HR+/HER2- advanced breast cancer remains on track for mid-2025; (ii) Abstract accepted to ASCO for update of Phase 1b ReDiscover trial of RLY-2608 + fulvestrant: Focus of the abstract is updated 600mg BID (fasted) doublet data with median follow-up now greater than 12 months...; (iii) Continued advancement of the ongoing triplet cohorts with RLY-2608 + fulvestrant + atirmociclib or ribociclib."

New P3 trial • P1 data • Trial status • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

TACTIVE-K: A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer. (clinicaltrials.gov) - P1/2 | N=65 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Targeting the Cell Cycle Machinery in Breast Cancer – Where to from Here? (GBCC 2025) - "Atirmociclib, a potent CDK4-selective inhibitor, has demonstrated early signs of clinical efficacy and reduced neutropenia in both preclinical models and early-phase trials, underscoring its potential as first-line or salvage therapy when combined with endocrine agents...Additionally, the variable toxicity profiles across agents highlight the need for caution until more robust evidence is available. In conclusion, as we deepen our understanding of cell cycle regulation in breast cancer, precision targeting of CDKs remains a cornerstone of therapeutic innovation"

Breast Cancer • Hematological Disorders • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • CCNE1

C4391022: A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment (clinicaltrials.gov) - P2 | N=333 | Active, not recruiting | Sponsor: Pfizer | Phase classification: P3 ➔ P2 | Trial completion date: Dec 2028 ➔ Jan 2028 | Trial primary completion date: Dec 2025 ➔ Jun 2025

Phase classification • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

A Study to Learn if the Study Medicine Called Carbamazepine Changes How the Body Processes PF-07220060 (clinicaltrials.gov) - P1 | N=14 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A CDK4-selective inhibitor puts the brakes on cancer cells. (PubMed, Cancer Cell) - "describe the discovery and preclinical testing of the first-in-class CDK4-selective inhibitor atirmociclib. By sparing CDK6, atirmociclib has the potential to ameliorate dose-limiting hematological toxicities that limit drug exposure and treatment continuity and, by extension, the antitumor efficacy of dual CDK4/6 inhibitors."

Journal • Hematological Disorders • Oncology

CDK4 selective inhibition improves preclinical anti-tumor efficacy and safety. (PubMed, Cancer Cell) - "This prompted us to develop atirmociclib (PF-07220060), a next-generation CDK4 selective inhibitor...Realized dose intensification led to greater CDK4 inhibition and deeper anti-tumor responses, pointing to CDK4 target coverage as a limiting factor of CDK4/6 inhibitor efficacy. We also highlight combinatorial agents that may counter acquired resistance to CDK4 selective inhibition and widen its clinical application."

Journal • Preclinical • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • HER-2

Randomized phase 2 window of opportunity trial of preoperative atirmociclib (PF-07220060) plus letrozole versus letrozole on Ki-67 tumor expression in postmenopausal women with HR+/HER2−breast cancer (SG-BCC 2025) - "n/a"

Clinical • P2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK6 • HER-2

Atirmociclib Plus Letrozole Demonstrates Preliminary Efficacy and Safety in HR+/HER2-Negative Metastatic Breast Cancer (OncLive) - P1/2a | N=337 | NCT04557449 | Sponsor: Pfizer | "A preliminary analysis of an ongoing phase 1/2a study (NCT04557449) evaluating the safety, tolerability, and efficacy of atirmociclib (PF-07220060) in combination with letrozole demonstrated preliminary antitumor activity and a favorable safety profile in treatment-naive patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer....Findings showed that. in the overall study population (n = 34), all confirmed responses were partial responses (PRs), leading to an overall response rate (ORR) of 58.8% (95% CI, 40.7%-75.4%). The clinical benefit rate (CBR), defined as ORR or stable disease (SD) lasting at least 24 weeks, was 94.1% (95% CI, 80.3%-99.3%). The median time to response was 3.7 months (range, 1.6-15.6), and the median duration of response (DOR) was not reached."

P1/2 data • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=186 | Recruiting | Sponsor: Pfizer | Trial completion date: Nov 2026 ➔ Mar 2027 | Trial primary completion date: May 2025 ➔ Aug 2025

Trial completion date • Trial primary completion date • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Prostate Cancer • Solid Tumor • CDKN2A • ER • HER-2

ReDiscover: First-in-Human Study of Mutant-selective PI3Kα Inhibitor, RLY-2608, As a Single Agent in Advanced Solid Tumor Patients and in Combination with Fulvestrant in Patients with Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=890 | Recruiting | Sponsor: Relay Therapeutics, Inc. | N=400 ➔ 890

Enrollment change • Breast Cancer • Endometrial Cancer • Head and Neck Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • BRCA1 • BRCA2 • HER-2 • PIK3CA

C4391001: Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (clinicaltrials.gov) - P1 | N=337 | Recruiting | Sponsor: Pfizer | Phase classification: P1/2 ➔ P1

Phase classification • Breast Cancer • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Liposarcoma • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • CCND1 • CD4 • CDKN2A

FourLight-3: Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease (clinicaltrials.gov) - P3 | N=1020 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

FourLight-3: Study of PF-07220060 With Letrozole in Adults With HR-positive HER2-negative Breast Cancer Who Have Not Received Anticancer Treatment for Advanced/Metastatic Disease (clinicaltrials.gov) - P3 | N=1020 | Not yet recruiting | Sponsor: Pfizer

New P3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

C4391022: A Study to Learn About the Study Medicine Called PF-07220060 in Combination With Fulvestrant in People With HR-positive, HER2-negative Advanced or Metastatic Breast Cancer Who Progressed After a Prior Line of Treatment (clinicaltrials.gov) - P3 | N=333 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=500 ➔ 333

Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR