prifetrastat (PF-07248144) / Pfizer - LARVOL DELTA

Phase 1/2a trial of prifetrastat in combination with vepdegestrant in patients (pts) with ER+/HER2− advanced/metastatic breast cancer (ABC): Results from dose escalation (ESMO 2026) - No abstract available

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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

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

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

Trial completion

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 | Initiation date: May 2026 ➔ Sep 2026

Biomarker • Trial initiation date • 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 About How Food Affects the Uptake of Study Medicine Prifetrastat Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=12 | Not yet recruiting | Sponsor: Pfizer

New P1 trial

A Study to Learn About How Different Forms of Study Medicine Prifetrastat Are Taken Up Into the Blood in Healthy Adults (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: Pfizer

New P1 trial

104 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 (Cancer Network) - "Up to 400 patients will be randomized (1:1) to receive either PF-07248144 plus fulvestrant vs everolimus plus endocrine therapy (fulvestrant or exemestane). Patients will be stratified by investigator choice of endocrine therapy with everolimus (fulvestrant vs exemestane), prior systemic lines of therapy in metastatic setting (1 vs 2), and disease site (visceral vs non-visceral). The primary end point is progression-free survival by blinded independent central review (BICR). Overall survival is a key secondary end point; other secondary end points include objective response, duration of response, clinical benefit rate, safety, and pharmacokinetics of PF-07248144."

Clinical protocol • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer

C4551017: A Study to Learn About How Different Forms of Study Medicine Prifetrastat are Taken Up Into the Blood in Healthy Adults (clinicaltrialsregister.eu) - P1 | N=32 | Not yet recruiting | Sponsor: Pfizer Inc.

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

Long-term safety results and adverse event (AE) management recommendations in patients with ER+/HER2− metastatic breast cancer (mBC) receiving prifetrastat, a first-in-class KAT6 inhibitor, at the recommended phase 3 dose (RP3D) of 5 mg once-daily (QD). (ASCO 2026) - P2, P3 | "In an ongoing phase 1/2a study (NCT04606446), prifetrastat has demonstrated encouraging antitumor activity and manageable safety when combined with fulvestrant (FUL) in patients with heavily pretreated ER+/HER2– mBC (Mukohara T, et al. After extended follow-up of the phase 1/2a study, the RP3D of prifetrastat (5 mg QD) maintained a manageable safety profile when dose modifications and supportive care measures were implemented for AEs such as neutropenia and dysgeusia. These AE management strategies have been incorporated into the ongoing phase 3 study (KATSIS-1; NCT07062965) in patients with HR+/HER2− mBC after progression on CDK4/6i-based therapy."

Adverse events • Clinical • Metastases • P3 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • Febrile Neutropenia • HER2 Breast Cancer • HER2 Positive Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • ER • HER-2 • KAT6A • KAT6B

UC-GMP-2504: 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 (clinicaltrialsregister.eu) - P1/2 | N=51 | Not yet recruiting | Sponsor: Unicancer

Biomarker • New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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

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

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

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) - "PRIFET 5 mg QD + FUL robustly inhibited KAT6 and ER signaling, resulting in early ctDNA clearance, including resistance-associated ESR1 variants. These findings further support PRIFET 5 mg QD + FUL as the recommended phase 3 regimen and provide mechanistic insight into overcoming ER resistance and inhibiting cell cycle/tumor proliferation in ER+/HER2− mBC. Integration of tumor and ctDNA PD markers offers a powerful approach for dose selection, patient stratification, and real-time monitoring of molecular response in future clinical trials."

Circulating tumor DNA • Metastases • Tumor mutational burden • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • AKT1 • CCNB1 • CCNE1 • ER • FOXD3 • HER-2 • KAT6A • MXI1 • PIK3CA • PTEN • TFF3 • TK1 • TMB • TYMS

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. (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Pfizer

Trial initiation date • 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 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 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion

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. (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Pfizer

Trial initiation date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA • BRCA1 • BRCA2 • ER • HER-2

Identification of novel KAT6A/B inhibitors with enhanced antitumor activity and reduced hematologic toxicity (AACR 2025) - "Additionally, the inhibition of H3K23 acetylation in ZR-75-1 cells was analyzed by Western blotting. HLX97-069/053 emerged as the top two candidates, exhibiting superior enzymatic inhibition and enhanced selectivity against KAT5/7/8, along with more potent cytotoxic effects in ZR-75-1 cells, in head-to-head comparisons with PF-07248144. In summary, these preclinical data provide compelling evidence that we have identified novel KAT6A/B inhibitors with best-in-class potential. Confirmation of the final candidate will depend on the outcomes of the forthcoming pilot toxicity studies, with an IND application anticipated by the end of 2025."

Breast Cancer • Oncology • Solid Tumor • KAT6A

C4551001: Study of PF-07248144 in Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P2 | N=320 | Recruiting | Sponsor: Pfizer | Phase classification: P1 ➔ P2 | Trial primary completion date: Feb 2028 ➔ Jul 2029

Phase classification • Trial primary 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

Discovery and development of IST-477, a selective KAT6A histone acetyl transferase inhibitor and characterization of its anti-tumor efficacy in ER+ HER2- breast cancer and other tumor indications (AACR 2025) - "An inhibitor of KAT6A and KAT6B, PF-07248144, has entered phase 2 clinical studies with durable partial responses reported in estrogen-receptor positive (ER+) HER2- breast cancer patients who had progressed on a prior endocrine therapy and CDK4/6 inhibitor (Mukohara et al, 2024, Nature Medicine 30:2242). Pharmacologic efficacy of this targeted therapeutic will be discussed with an analysis of the relationship to KAT6A and 6B expression in these models. All IND-enabling studies to support clinical progression of IST-477 are planned for completion in mid-2025."

Clinical • Epigenetic controller • Breast Cancer • Esophageal Cancer • Estrogen Receptor Positive 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 • ER • HER-2 • KAT6A • KAT6B

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

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