atirmociclib (PF-07220060) / Pfizer - LARVOL DELTA

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

International phase 3 clinical trial evaluating PF-07220060 plus fulvestrant in patients with HR+/HER2− advanced/metastatic breast cancer with progression after a prior CDK4/6 inhibitor. (ASCO 2024) - P3 | "Approximately 500 patients will be randomly assigned (1:1) to receive PF-07220060 (orally and continuously in a 28-day cycle) plus fulvestrant (intramuscular injection on days 1 and 15 of cycle 1 and then on day 1 of each cycle thereafter) or investigator's choice of fulvestrant alone or everolimus plus exemestane, which must be declared before randomization. JCO. 2023; 41:3009."

Clinical • Metastases • P3 data • 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 • BRCA • ER • HER-2 • PIK3CA • PTEN

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

OP-1250-003: Phase 1b Study of OP-1250 (Palazestrant) in Combination With Ribociclib, Alpelisib, Everolimus, or Atirmociclib in ER+, HER2- Breast Cancer (clinicaltrials.gov) - P1 | N=190 | Active, not recruiting | Sponsor: Olema Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • 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 • ER • 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=235 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Aug 2026 ➔ Feb 2027 | Trial primary completion date: Aug 2026 ➔ Feb 2027

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

Development and ICH M10-compliant validation of an LC-MS/MS method for quantification of atirmociclib in mouse plasma and its application to preclinical pharmacokinetic studies. (PubMed, J Chromatogr B Analyt Technol Biomed Life Sci) - "The analyte (atirmociclib) and internal standard (warfarin) were detected using Q1/Q3 (m/z) mass transitions 464.2/303.9 and 309.0/163.0 respectively. All validation parameters, including stability in biological matrices and solution, met the predefined acceptance criteria. This sensitive, and reproducible method was successfully applied to support preclinical pharmacokinetic study of atirmociclib in mouse, providing a valuable analytical tool."

Journal • PK/PD data • Preclinical • 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 • 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) - P2 | "Conclusions At 24.8 months of follow-up, ATI + LET continues to show favorable safety/tolerability and promising efficacy when used as 1L treatment in pts with HR+/HER2− mBC. A randomized phase 3 trial of ATI + LET has been initiated based on these data."

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

First-in-human first-in-class phase 1/2a study of the next generation CDK4-selective inhibitor PF-07220060 in patients (pts) with advanced solid tumors, enriched for HR+ HER2- mBC who progressed on prior CDK4/6 inhibitors and endocrine therapy. (ASCO 2023) - P1/2 | " At data cut off (Nov 1, 2022), 34 pts with advanced solid tumors received PF-07220060 in monotherapy dose escalation (Part 1A: 100–500 mg BID), and 26 pts with HR+/HER2- mBC in combination (300mg/400mg BID) with letrozole or fulvestrant (Parts 1B + 1C). PF-07220060 + ET showed efficacy in pts with HR+/HER2- mBC who progressed on prior CDK4/6i+ET. Tolerability of PF-07220060 alone and in combination with ET was encouraging. Dose expansions with PF-07220060 + ET in pts with HR+/HER2- mBC post CDK4/6i and in CDK4/6i naïve pts are ongoing."

Clinical • Metastases • P1/2 data • Breast Cancer • Hematological Disorders • HER2 Breast Cancer • Leukopenia • Neutropenia • Oncology • Solid Tumor • Thrombocytopenia • HER-2

Efficacy and safety of atirmociclib (ATI) + fulvestrant (FUL) in patients (pts) with HR+/HER2– advanced/metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitor (CDK4/6i) in a randomized phase 2 study (FOURLIGHT-1) (ESMO 2026) - No abstract available

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

Neoadjuvant atirmociclib plus letrozole versus letrozole alone in HR+/HER2− breast cancer: Results from FourLight-2, a randomized phase 2 window of opportunity study. (ASCO 2026) - P2 | "ATI + LET demonstrated substantially greater antiproliferative effects than LET alone, with a tolerable safety profile in pts with HR+/HER2− BC, suggesting that ATI + LET may have value in early BC."

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

First-in-human phase I/IIa study of the first-in-class, next-generation CDK4-selective inhibitor PF-07220060 in combination with endocrine therapy (ET) in patients (pts) with HR+/HER2- metastatic breast cancer (mBC) who progressed on prior CDK4/6 inhibitors (CDK4/6i): Safety and efficacy update (ESMO-BC 2024) - P1/2 | "Results At data cutoff (Nov 1, 2023), 33 pts received PF-07220060 (300mg/400mg BID) in combination with letrozole or fulvestrant (Parts 1B + 1C). Confirmed objective responses (PRs) were observed irrespective of ESR1 or PI3K pathway mutations. Conclusions PF-07220060 + ET showed a favorable safety profile with few hematologic adverse events and infrequent dose modifications, and promising efficacy despite prior CDK4/6i treatment, irrespective of key mutations."

Clinical • Combination therapy • Metastases • P1/2 data • Breast Cancer • Hematological Disorders • HER2 Positive Breast Cancer • Neutropenia • Oncology • Solid Tumor • CDK6 • CDKN2A • ER • HER-2

Study About Whether Atirmociclib/PF-07220060 Proportionally Increases Exposure as Dose Increases in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Pfizer | Recruiting ➔ Completed

Trial completion

A Study to Learn How the Study Medicine Called Atirmociclib is Handled by the Body in People With Normal Liver Function and Different Levels of Liver Disease (clinicaltrials.gov) - P1 | N=28 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatitis C • Hepatology • Liver Failure

Recent Progress (GlobeNewswire) - "(i) Completed enrollment in the pivotal Phase 3 OPERA-01 trial of palazestrant as a monotherapy in patients with second or third-line estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer (MBC)...; (ii) Completed enrollment in the Phase 1b/2 study of palazestrant in combination with atirmociclib in ER+/HER2- MBC."

Enrollment closed • Estrogen Receptor Positive Breast Cancer • HER2 Negative Breast Cancer

Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=792 | Recruiting | Sponsor: Hoffmann-La Roche | N=56 ➔ 792

Enrollment change • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

Morpheus-TNBC: A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Metastatic or Locally Advanced Breast Cancer (clinicaltrials.gov) - P1/2 | N=1132 | Recruiting | Sponsor: Hoffmann-La Roche | N=792 ➔ 1132

Enrollment change • Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • PD-L1

PIKture-01: First-in-Human Study of OKI-219 in Advanced Solid Tumors and Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=200 | Active, not recruiting | Sponsor: OnKure, Inc. | Recruiting ➔ Active, not recruiting | Trial primary completion date: Jun 2026 ➔ Dec 2026

Enrollment closed • First-in-human • Monotherapy • Trial primary completion date • Breast Cancer • Colorectal Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • HER-2 • KRAS • PI3K

Study to Assess the Safety and Tolerability of PF-07220060 in Combination With PF-07104091 in Participants With Breast Cancers or Solid Tumors and to Assess the Safety and Tolerability of PF-07220060 and PF-07104091 in Combination With Endocrine Therapy in Participants With Breast Cancer. (clinicaltrials.gov) - P1b/2 | N=144 | Recruiting | Sponsor: Pfizer | Trial completion date: Oct 2027 ➔ Jan 2028 | Trial primary completion date: Oct 2026 ➔ Jan 2027

Combination therapy • 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

Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (clinicaltrials.gov) - P1; N=118; Recruiting; Sponsor: Pfizer; N=52 ➔ 118; Trial completion date: Mar 2024 ➔ Apr 2025; Trial primary completion date: Mar 2024 ➔ Apr 2025

Clinical • Combination therapy • Enrollment change • Trial completion date • Trial primary completion date • Breast 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 • Prostate Cancer • Sarcoma • Solid Tumor • CCND1 • CD4

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

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) - P1b/2 | N=144 | Recruiting | Sponsor: Pfizer | Trial completion date: Jul 2027 ➔ Sep 2026

Trial 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

Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (clinicaltrials.gov) - P1/2 | N=337 | Recruiting | Sponsor: Pfizer | Trial completion date: Oct 2027 ➔ May 2028 | Trial primary completion date: Aug 2026 ➔ Mar 2027

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast 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 • Prostate Cancer • Sarcoma • Solid Tumor • CCND1 • CD4 • CDKN2A

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=240 | Recruiting | Sponsor: Pfizer | Trial completion date: Sep 2026 ➔ Dec 2026 | Trial primary completion date: Sep 2026 ➔ Dec 2026

Combination therapy • 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

Study to Test the Safety and Tolerability of PF-07220060 in Participants With Advance Solid Tumors (clinicaltrials.gov) - P1/2 | N=337 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2026 ➔ Sep 2027 | Trial primary completion date: Feb 2026 ➔ Jul 2026

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast 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 • Prostate Cancer • Sarcoma • Solid Tumor • CCND1 • CD4 • CDKN2A

Study to Assess the Safety and Tolerability of PF-07220060 in Combination With PF-07104091 in Participants With Breast Cancers or Solid Tumors and to Assess the Safety and Tolerability of PF-07220060 and PF-07104091 in Combination With Endocrine Therapy in Participants With Breast Cancer. (clinicaltrials.gov) - P1b/2 | N=144 | Recruiting | Sponsor: Pfizer | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • 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