P1, N=6, Active, not recruiting, Pfizer | Trial completion date: Sep 2024 --> Mar 2025

P1, N=12, Not yet recruiting, Pfizer

P1, N=52, Completed, Pfizer | Active, not recruiting --> Completed

P1, N=6, Active, not recruiting, Pfizer | Trial completion date: Mar 2024 --> Sep 2024

We developed and validated a sensitive and rapid liquid chromatography-tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs.

P2, N=152, Completed, Arvinas Inc. | Active, not recruiting --> Completed

P3, N=560, Recruiting, Pfizer | Trial primary completion date: Aug 2024 --> Nov 2024

Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and ESR1 mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers.Clinical trial registration: NCT05654623 (ClinicalTrials.gov).

Tamoxifen and fulvestrant represent standard therapy options in estrogen-mediated disease but have their own limitations. Isatin-based triple angiokinase inhibitor BIBF1120 (Nintedanib) and multikinase inhibitor Sunitinib (Sutent) have been approved by the FDA...Finally, molecular dynamics (MD) simulations indicated stable behavior of the protein-ligand complex between ERα and its ligand 5i. Overall, these results suggest that the new isatin derivative 5i holds promise as a new ERα degrader.

P1, N=52, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P3, N=1180, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

P1, N=12, Completed, Pfizer | Recruiting --> Completed

Vepdegestrant achieved greater ER degradation in-vivo compared to fulvestrant, which correlated with improved tumor growth inhibition, suggesting vepdegestrant could be a more effective backbone ET for patients with ER+/HER2- breast cancer.

P1, N=15, Completed, Pfizer | Recruiting --> Completed

P1/2, N=217, Active, not recruiting, Arvinas Estrogen Receptor, Inc. | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Sep 2024

Distinct functional disparities between estrogen subtypes emerge, with estradiol synergistically promoting ER+ BC cell growth with LINC00173, while estrone (E1) facilitated LITAF-transcriptional activation. In terms of therapeutic significance, silencing LINC00173 alongside moderate addition of E1 heightened TNFα and induced apoptosis, effectively inhibiting ER+ BC progression.

P1, N=48, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P1/2, N=67, Recruiting, Pfizer | Trial completion date: Aug 2027 --> Jan 2027 | Trial primary completion date: Feb 2027 --> Jul 2026

P1, N=21, Terminated, Accutar Biotechnology Inc | N=30 --> 21 | Trial completion date: Dec 2024 --> Apr 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2024 --> Apr 2024; Voluntarily terminate the study since the sponsor's development strategy was adjusted.

P1, N=30, Active, not recruiting, Accutar Biotechnology Inc | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Jan 2024 --> Dec 2024

P1, N=48, Not yet recruiting, Pfizer

P1, N=16, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P1/2, N=67, Recruiting, Pfizer | Trial completion date: Feb 2027 --> Aug 2027 | Trial primary completion date: Aug 2026 --> Feb 2027

P1, N=12, Recruiting, Pfizer | Not yet recruiting --> Recruiting

P1/2, N=47, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2 | N=35 --> 47 | Trial completion date: Oct 2027 --> Dec 2026 | Trial primary completion date: Apr 2026 --> Dec 2026

P1/2, N=65, Recruiting, Pfizer | Not yet recruiting --> Recruiting | Trial completion date: Nov 2026 --> Feb 2026 | Trial primary completion date: May 2026 --> Aug 2025

P1/2, N=67, Recruiting, Pfizer | Phase classification: P2 --> P1/2

P1, N=12, Not yet recruiting, Pfizer

P1/2, N=40, Recruiting, Pfizer | Phase classification: P1b/2 --> P1/2 | Trial completion date: Jun 2027 --> Dec 2025

P2, N=67, Recruiting, Pfizer

P1, N=16, Not yet recruiting, Pfizer

P2, N=67, Recruiting, Pfizer | Not yet recruiting --> Recruiting

As of the end of 2022, more than 20 drugs have entered clinical trials, with ARV-471 targeting estrogen receptor (ER) showing remarkable progress by entering phase III clinical studies...In this review, we aimed to update the PROTAC degraders as potential anticancer agents covering articles published in 2022. The design strategies, degradation effects, and anticancer activities were highlighted, which might provide an updated sight to develop novel PROTAC degraders with great potential as anticancer agents as well as favorable drug-like properties.

P1, N=6, Terminated, Accutar Biotechnology Inc | Trial completion date: Dec 2024 --> Sep 2023 | Active, not recruiting --> Terminated; Voluntarily terminate the study since the sponsor's development strategy was adjusted.

P1, N=32, Active, not recruiting, Arvinas Estrogen Receptor, Inc. | Recruiting --> Active, not recruiting | Phase classification: P1b --> P1

P2, N=152, Active, not recruiting, Arvinas Inc. | Recruiting --> Active, not recruiting

P1, N=9, Active, not recruiting, Pfizer | Trial primary completion date: Nov 2023 --> Mar 2024

P1, N=12, Completed, Pfizer | Active, not recruiting --> Completed

P1/2, N=65, Not yet recruiting, Pfizer

P1, N=12, Active, not recruiting, Pfizer | Recruiting --> Active, not recruiting

Modulation of estrogen activity with therapeutics such as tamoxifen and aromatase inhibitors have been the mainstay therapeutic strategy for ER-positive breast cancer. Several ER-directed therapies have been developed to antagonize the oncogenic ER function, including Selective ER Degraders (SERDs) such as fulvestrant which is approved to treat patients with advanced or metastatic breast cancer...Enrollment began in December 2022 with five sites in the United States planned. NCT05654532.

Eligible patients (aged ≥18 years) must have histologically or cytologically confirmed ER+/HER2- locoregionally recurrent or metastatic breast cancer, with no prior treatment in the advanced setting, and no prior treatment in any setting with CDK4/6 inhibitors, vepdegestrant, fulvestrant, elacestrant, or other investigational agents (including novel endocrine therapy, selective ER degraders, selective ER covalent antagonists, and complete ER antagonists). The primary efficacy endpoint of the phase 3 portion is progression-free survival based on blinded independent central review. Enrollment began June 2023 and is ongoing.