prifetrastat (PF-07248144) / Pfizer - LARVOL DELTA

Discovery of a highly potent and selective KAT6A degrader ATH-002 that demonstrates robust anti-tumor activity with a low risk of hematotoxicity in preclinical studies (AACR 2026) - "PF-07248144, the first KAT6A/6B dual inhibitor to enter the clinic, demonstrates durable anti-tumor activity in ER+HER2− metastatic breast cancer, especially in combination with fulvestrant. Besides monotherapy, ATH-002 displayed an enhanced anti-proliferation effect in combination with SERDs or CDK4/6 inhibitors without overlapping hematotoxicity, implying a potential application of KAT6A degrader and SOC therapy. Collectively, our findings support ATH-002 as a clinical candidate for the treatment of KAT6A-amplified tumors."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B • KMT2A • PARP1

A Study to Learn if Itraconazole Changes How the Body Processes PF-07248144 (Study Medicine) (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed

KAT6i prifetrastat combines with PI3K pathway inhibitors to drive superior efficacy in preclinical models of PIK3CA mutated ER+ BC (AACR 2026) - "In vitro drug combination studies demonstrate synergy between prifetrastat and several PI3Kα inhibitors including alpelisib and inavolisib as well as mutant selective PI3Kα inhibitors such as tersolisib across cell lines harboring PIK3CA helical or kinase domain mutations. Finally, the triple combination of prifetrastat + Fulvesterant with PI3Kα inhibitors drives deeper tumor growth inhibition in PIK3CA mutant ER+ PDX models in vivo. Overall, we find that KAT6A/B inhibitors can effectively be combined with PI3Kα inhibitors and endocrine therapy to further drive efficacy in PIK3CA-mutant ER+BC indicating that the triplet combination could present a promising therapeutic option for this population."

Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • KAT6A • KAT6B • PIK3CA

A highly selective KAT6/7 dual inhibitor with best-in-class potential and favorable pharmacokinetic profile (AACR 2026) - "In ER+ breast cancer cells, KC1086 durably suppressed H3K23ac/H3K14ac, which outperformed PF-07248144 on biomarker depth and duration...Combinations of KC1086 further demonstrated enhanced efficacy: (i) with Palbociclib (CDK4/6 inhibitor) (TGI 101%) in ZR-75-1 ER+ breast cancer xenograft model; (ii) with Fulvestrant (Estrogen Receptor Antagonist) (TGI 83%) in xxT47D breast cancer models yielding tumor regressions and survival benefit. Furthermore, KC1086 demonstrated favorable PK profile and significant safety window: linear PK, high oral bioavailability, minimum drug accumulation and clean safety pharmacology (eg. CV, CNS and respiratory).In conclusion, we demonstrated equipotent dual inhibition of KAT6/7 delivering potentially deeper chromatin closure than KAT6-selective blockade, which translated into robust monotherapy activity and combination synergy across ER+ breast cancer, ovarian cancer as well as other tumor models, with favorable preclinical safety. These data..."

PK/PD data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Ovarian Cancer • Solid Tumor • HER-2 • KAT6A

Unlocking endocrine resistance: Co-targeting KAT6 and ER with prifetrastat (PF-07248144) and fulvestrant drives tumor and ctDNA response in ER+/HER2− metastatic breast cancer (AACR 2026) - "Abstract is embargoed at this time."

Circulating tumor DNA • Metastases • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Dose optimization of PF-07248144, a first-in-class KAT6 inhibitor, in patients (pts) with ER+/HER2− metastatic breast cancer (mBC): Results from phase 1 study to support the recommended phase 3 dose (RP3D). (ASCO 2025) - P1 | "To inform the RP3D, we evaluated two pharmacokinetically distinguishable doses of PF-07248144 in combination with fulvestrant (FUL) from a phase 1 study in ER+/HER2− mBC in a dose expansion phase... Based on a thorough benefit–risk assessment of two pharmacokinetically distinguishable doses with sufficient number of pts and follow up, 5 mg QD PF-07248144 was identified as the optimal dose in combination with FUL with acceptable safety and encouraging activity. A pivotal phase 3 trial is planned to address the high unmet medical need in ER+/HER2− mBC after progression on CDK4/6i plus ET."

Clinical • Metastases • P1 data • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Febrile Neutropenia • HER2 Breast Cancer • HER2 Positive Breast Cancer • Neutropenia • Oncology • Pneumonia • Solid Tumor • CDK4 • ER • HER-2

KATSIS-1: Randomized phase 3 trial evaluating KAT6 inhibitor PF-07248144 (prifetrastat) plus fulvestrant in HR+HER2− advanced/metastatic breast cancer after progression on CDK4/6 inhibitor-based therapy (MBCC 2026) - No abstract available

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

C4551007: A Study to Learn if Multiple Doses of the Study Medicine Called Carbamazepine Changes How the Body Processes the Other Study Medicine PF-07248144 (clinicaltrialsregister.eu) - P1 | N=12 | Completed | Sponsor: Pfizer Inc.

New P1 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Oncology • Solid Tumor

C4551002: A Study to Learn About the Study Medicine Called PF-07248144 in Combination with Fulvestrant in People with HR-positive, HER2-negative Advanced or Metastatic Breast Cancer who Progressed After a Prior Line of Treatment. (clinicaltrialsregister.eu) - P2/3 | N=153 | Recruiting | Sponsor: Pfizer Inc.

New P2/3 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • ER • HER-2

A Study to Understand What the Body Does to the Study Medicine Called PF-07248144 When Taken by Healthy Adults (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Pfizer

New P1 trial

KAT6 inhibitors under investigation for solid tumors: the preclinical and early phase progress. (PubMed, Expert Opin Investig Drugs) - "Prifetrastat in combination with Fulvestrant is now being evaluated in a phase III trial for pretreated ER+ advanced breast cancer. Additionally, mitigation strategies for dysgeusia and clinically available response-predictive biomarkers should be developed. KAT6 inhibitors with different target spectra, including KAT6A-selective and KAT6/7 inhibitors, may exhibit differential efficacy and safety profiles, offering deeper insights into KAT6-targeted therapy."

Journal • Preclinical • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • KAT6A • KAT6B

Dancing with KAT6A: Current advances and therapeutic potential in oncology of KAT6A inhibitors. (PubMed, Bioorg Chem) - "PF-07248144 has shown antitumor activity in estrogen receptor-positive (ER+) breast cancer models and is currently undergoing clinical evaluation...This review provides a comprehensive overview of the structural and biological functions of KAT6A, its role in tumor progression, and the therapeutic potential of its inhibition. It summarizes the advancements in KAT6A inhibitor development from 2019 to the present, emphasizing the optimization processes from lead compounds to clinical candidates."

Journal • Review • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • KAT6A

Inhibition of lysine acetyltransferase KAT6 in ER+HER2- metastatic breast cancer: a phase 1 trial. (PubMed, Nat Med) - P1 | "In the present study, we report the safety, pharmacokinetics (PK), pharmacodynamics, efficacy and biomarker results from the first-in-human, phase 1 dose escalation and dose expansion study (n = 107) of PF-07248144 monotherapy and fulvestrant combination in heavily pretreated ER+ human epidermal growth factor receptor-negative (HER2-) metastatic breast cancer (mBC). These findings establish KAT6A and KAT6B as druggable cancer targets, provide clinical proof of concept and reveal a potential avenue to treat mBC. clinicaltrial.gov registration: NCT04606446 ."

Journal • Metastases • P1 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B

A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer. (ASCO 2024) - P1 | "We report the clinical safety, efficacy, PK, PD, and biomarker results of a phase 1 dose expansion study (NCT04606446) of PF-07248144 as monotherapy and in combination with fulvestrant in heavily pretreated ER+ HER2− metastatic breast cancer (mBC). PF-07248144 demonstrated a tolerable safety profile and durable efficacy in pts with heavily pretreated ER+ HER2− mBC with and without ESR1 or PIK3CA/AKT1/PTEN mutations. We have provided strong clinical proof of concept targeting KAT6, a novel epigenetic target and opened a new avenue to treat ER+ HER2− mBC."

Clinical • Metastases • P1 data • Anemia • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • AKT1 • ER • HER-2 • PIK3CA • PTEN

A Study to Learn if Itraconazole Changes How the Body Processes PF-07248144 (Study Medicine) (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open

EPIBREAST: Clinical Trial Evaluating the Biological Activity of a New Drug Identified as Prifetrastat (PF-07248144), Combined With Fulvestrant for the Treatment of Patients With Hormone Receptor Positive (HR+) and HER2 Negative (HER2-) Breast Cancer Extended to Other Organs. (clinicaltrials.gov) - P2 | N=51 | Not yet recruiting | Sponsor: UNICANCER

Biomarker • New P2 trial • Tumor mutational burden • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Melanoma • Oncology • Solid Tumor • ER • HER-2

A Study to Learn if Itraconazole Changes How the Body Processes PF-07248144 (Study Medicine) (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A phase 1/2 trial evaluating the safety, tolerability, and efficacy of the KAT6 inhibitor, PF-07248144, in combination with vepdegestrant in patients with ER+/HER2− locally advanced or metastatic breast cancer (SABCS 2025) - P1 | "Patients may have received fulvestrant. Primary endpoints are dose-limiting toxicities (Part 1E only), safety, and tolerability. Secondary endpoints include pharmacokinetics of PF-07248144 and vepdegestrant in both Parts 1E and 2E, and best overall response, duration of response, clinical benefit rate, progression-free survival, time to progression, and overall survival in Part 2E."

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B

Randomized phase 3 trial evaluating KAT6 inhibitor PF-07248144 plus fulvestrant in HR+HER2− advanced/metastatic breast cancer after progression on CDK4/6 inhibitor-based therapy (SABCS 2025) - " This open-label, randomized phase 3 trial is comparing PF-07248144 plus FUL versus everolimus (EVE) plus ET [FUL or exemestane (EXE)]) in patients with HR+HER2− ABC. The primary endpoint is progression-free survival by blinded independent central review. Overall survival is a key secondary endpoint; other secondary endpoints include objective response, duration of response, clinical benefit rate, safety, and pharmacokinetics of PF-07248144."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • KAT6A • KAT6B • PIK3CA • PTEN

Dose optimization of PF-07248144, a first-in-class KAT6 inhibitor, in patients with ER+/HER2− metastatic breast cancer: results from phase 1 study to support the recommended phase 3 dose (SABCS 2025) - "Based on a thorough benefit-risk assessment of two pharmacokinetically distinguishable doses with sufficient number of patients and follow up, 5 mg QD PF-07248144 was identified as the optimal dose in combination with FUL with acceptable safety and encouraging activity. A pivotal phase 3 trial is ongoing to address the high unmet medical need in ER+/HER2− mBC after progression on CDK4/6i plus ET."

Clinical • Metastases • P1 data • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2

Randomized phase 3 trial evaluating KAT6 inhibitor PF-07248144 plus fulvestrant in HR+HER− advanced/metastatic breast cancer after progression on CDK4/6 inhibitor-based therapy (ESMO 2025) - "Trial design This open-label, randomized phase 3 trial is evaluating PF-07248144 plus FUL versus everolimus (EVE) plus ET [FUL/exemestane (EXE)]) in patients with HR+HER2− ABC. The primary endpoint is progression-free survival by blinded independent central review. Overall survival is a key secondary endpoint; other secondary endpoints include objective response, duration of response, clinical benefit rate, safety, and pharmacokinetics of PF-07248144."

Clinical • Metastases • P3 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • KAT6A • KAT6B • PIK3CA • PTEN

PF-07248144 – First-in-class potent, selective KAT6i in ER+HER2−breast cancer (AACR-NCI-EORTC 2025) - "In the Ph1 study, PF-07248144 + Fulvestrant demonstrated deep and durable anti-tumor activity with 37.2% ORR and 10.7 months mPFS. Based on the strength of these data, a pivotal Ph3 trial of PF-07248144 + Fulvestrant is planned in HR+HER2- mBC after progression on CDK4/6i + ET."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • KAT6A • KAT6B • PIK3CA

PF-07248144 – First-in-class potent, selective KAT6i in ER+HER2− breast cancer (AACR-NCI-EORTC 2025) - "In the Ph1 study, PF-07248144 + Fulvestrant demonstrated deep and durable anti-tumor activity with 37.2% ORR and 10.7 months mPFS. Based on the strength of these data, a pivotal Ph3 trial of PF-07248144 + Fulvestrant is planned in HR+HER2- mBC after progression on CDK4/6i + ET."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2 • KAT6A • KAT6B • PIK3CA

A Study to Learn if Multiple Doses of the Study Medicine Called Carbamazepine Changes How the Body Processes the Other Study Medicine PF-07248144 (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: Pfizer

New P1 trial

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