atirmociclib (PF-07220060) / Pfizer - LARVOL DELTA

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 • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Targeted Protein Degradation

Effect of atirmociclib plus endocrine therapy (ET) on serum thymidine kinase activity (TKa) in a phase 1 study of patients with HR+/HER2_ metastatic breast cancer (mBC) (ESMO-BC 2025) - No abstract available

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor

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

Characterization of BTX-9341, a bifunctional degrader of CDK4 and CDK6 for HR+/HER2- breast cancer. (SABCS 2024) - "CDK4/6 inhibitors (CDK4/6i) such as palbociclib, abemaciclib and ribociclib are used to treat HR+/HER2- breast cancer, but patients can develop resistance via many mechanisms, several of which converge on upregulation of the cyclin D-CDK4/6 signaling node...BTX-9341 mediated downregulation of CDK2 and cyclin E1, which are known to drive resistance to CDK4/6i, was more pronounced and more sustained than that mediated by CDK4/6 inhibitors including approved inhibitors such as palbociclib and inhibitors under clinical development such as PF-07220060...These results indicate that utilizing a degrader such as BTX-9341 may be more effective in a post CDK4/6i setting than switching to a new CDK4/6 inhibitor. Based on this data, we have initiated a Phase 1 clinical trial with BTX-9341 as a monotherapy and in combination with fulvestrant, for HR+/HER2- breast cancer patients who have progressed on CDK4/6i therapy."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • CDK2 • CDK4 • CDK6 • CRBN • ER • HER-2

Preclinical characterization of BGB-43395, a potential best-in-class CDK4 selective inhibitor with potent pharmacodynamic and anti-tumor activity in HR+HER2- breast cancer models (SABCS 2024) - P1 | "In the biochemical assay, BGB-43395 exhibits superior kinase inhibition against CDK4 compared to approved CDK4/(6) inhibitors (palbociclib, ribociclib and abemaciclib) and investigational CDK4 inhibitor PF-07220060...BGB-43395 in combination with fulvestrant also demonstrated a greater tumor growth inhibition compared to palbociclib in combination with fulvestrant in HR+HER2- MCF7 xenograft models. In summary, BGB-43395 is a potential best-in-class CDK4 inhibitor with high potency and selectivity over CDK6 and other kinases, providing an opportunity to achieve high exposure and thus maximum on-target CDK4 inhibition for the treatment of HR+HER2- breast cancer and other CDK4 dependent cancers. BGB-43395 is currently undergoing clinical investigation as monotherapy or in combination with endocrine therapies in patients with metastatic HR+HER2- BC and other advanced solid tumors (NCT06120283)."

PK/PD data • Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • RB1

Pfizer Showcases Scientific Leadership in Breast Cancer…at…SABCS (Pfizer Press Release) - "Key SABCS Presentations: Data from 30 company-sponsored, investigator-sponsored, and collaborative research abstracts will be presented at SABCS, including nine real-world analyses affirming IBRANCE (palbociclib) as a first-line standard-of-care treatment for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). The company will also present new data from its expanding pipeline of innovative, next-generation therapy candidates that have the potential to address critical unmet patient needs across all subtypes and stages of breast cancer, including new and updated Phase 1 data for atirmociclib, vepdegestrant, and the novel KAT6 inhibitor, PF-07248144."

Clinical data • Real-world • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Expansion Study Collaboration Updates (Businesswire) - "Scorpion Therapeutics and Pfizer Inc...entered into a new clinical trial collaboration and supply agreement to evaluate atirmociclib...in combination with STX-478 and fulvestrant in patients with PI3Kα-mutated, HR+/HER2- metastatic breast cancer in the frontline metastatic setting. Under the terms of the agreement, Scorpion and Pfizer will equally share the development costs of the study. In addition, Pfizer will supply atirmociclib for use in the study and Scorpion will manage the conduct of the study. The STX-478 + atirmociclib + fulvestrant triplet combination is planned to begin in 2H25."

Commercial • Trial status • Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

Randomized phase 2 window of opportunity trial comparing the effect of preoperative atirmociclib (PF-07220060) plus letrozole versus letrozole alone on Ki-67 tumor expression in postmenopausal women with HR+/HER2+ breast cancer (SABCS 2024) - P2 | "Assessment of changes in the tumor microenvironment using spatial omics, and evaluation of the association between tumor gene expression profiles and treatment outcomes will be exploratory objectives. Enrollment is to begin July 2024 (NCT06465368)."

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

The next-generation CDK4-selective inhibitor atirmociclib (PF-07220060) in combination with letrozole as first-line treatment in patients with HR+/HER2+ metastatic breast cancer (SABCS 2024) - "Combination of atirmociclib + letrozole showed favorable safety/tolerability and promising early activity as first-line treatment in patients with HR+/HER2– mBC."

Clinical • Combination therapy • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK6 • CDKN2A • HER-2

C4391002: A Study to Learn About the Study Medicine (Called PF-07220060 in Combination With PF-07104091) In Participants With Breast Cancer and Solid Tumors (clinicaltrials.gov) - P1/2 | N=192 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2026 ➔ Aug 2026 | Trial primary completion date: Dec 2026 ➔ Aug 2026

Combination therapy • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Longitudinal circulating tumor DNA (ctDNA) dynamics in phase I/IIa study of the first-in-class CDK4-selective inhibitor, PF-07220060, in combination with endocrine therapy in patients with HR+/HER2− metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitors (ESMO 2024) - P1/2 | "We present data from the exploratory ctDNA analysis of the study. ctDNA samples were collected at baseline (cycle 1, day 1 [C1D1]), C1D15 and end-of-treatment (EOT) in patients (pts) with HR+/HER2− mBC treated with oral 300 or 400 mg BID PF-07220060, with fulvestrant (Part 1B, n=18) or letrozole (Part 1C, n=15) and analyzed with the Guardant360 platform (Guardant Health). Longitudinal ctDNA profiling enabled the identification of key genetic alterations and demonstrated that PF-07220060 plus ET may benefit pts with or without ESR1 and PI3K pathway mutations. Early ctDNA MR trended with favorable clinical outcomes, while pts with undetectable ctDNA on treatment had improved PFS."

Circulating tumor DNA • Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN • TP53

Synergistic preclinical efficacy through combination of the CDK4 and CDK2 selective inhibitors, PF-07220060 and PF-07104091, respectively, in HR+ HER2- breast cancer (ESMO 2024) - P1/2 | "Combining the highly selective CDK2i (PF-07104091) and CDK4i (PF-07220060) for HR+/HER2- breast cancer circumvents inhibition of CDK6, resulting in less hematologic toxicity. Further, increased anti-tumor efficacy and tumor regression seen with this combination (unlike with the single agents, or the combination of CDK2i and palbociclib) provide the rationale for the current clinical trial NCT05262400."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CCNE1 • CDK4 • CDKN2A • HER-2 • RB1

Phase Ib/II first-in-class novel combination trial of next generation CDK4-selective inhibitor PF-07220060 and next generation CDK2-selective inhibitor PF-07104091 in HR+ HER2- metastatic breast cancer and advanced solid tumors (ESMO 2024) - P1/2 | "BC pts could start fulvestrant at Cycle 3. PF-60/PF-91 combination was generally well tolerated with promising antitumor activity in heavily pretreated post-CDK4/6i mBC pts, including 5 PRs in mBC pts with ESR1 mutations and mPFS 8.3 months. Dose expansions are enrolling CDK4/6i-treated and naïve mBC pts."

Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2