On May 2, 2023 Arvinas, Inc. (Nasdaq: ARVN) and Quantum Leap Healthcare Collaborative reported that Arvinas’ vepdegestrant (ARV-471), a novel PROTAC estrogen receptor (ER) protein degrader being co-developed with Pfizer Inc. will be evaluated in the ongoing I-SPY TRIAL endocrine program sponsored by Quantum Leap (Press release, Arvinas, MAY 2, 2023, View Source [SID1234630825]). This study targets patients with newly diagnosed ER positive invasive cancer. Vepdegestrant is in Phase 3 clinical development for the treatment of patients with locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer.

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The I-SPY-2 Endocrine Optimization Platform (EOP) study (NCT01042379) will include a vepdegestrant monotherapy arm and a vepdegestrant in combination with letrozole arm. This study is focused on patients with clinically high-risk (stage 2/3) ER+/HER2- breast cancer, but molecularly low risk (MammaPrint low risk signature), a subset of patients with substantial risk for late recurrence.

Quantum Leap opened the EOP program in 2021 to specifically assess treatment options for this subset of patients, and work to find an early endpoint to measure the success of therapy. EOP is a sub-study within the main I-SPY-2 clinical trial utilizing neoadjuvant endocrine therapy in patients whose tumors are predicted to be sensitive to endocrine therapy but for whom chemotherapy is expected to provide little or no benefit.

"I-SPY TRIALs focus on high-impact experimental treatments that may benefit patients, providers, and researchers, and Arvinas is thrilled to be part of this innovative I-SPY-2 clinical trial," said John Houston, Ph.D., president and chief executive officer at Arvinas. "There is an unmet medical need for novel agents in life-threatening diseases and this research is vital to advancing patient outcomes. In all of our investigational research, our commitment is to patient safety and care, and we are excited by vepdegestrant’s potential to become a new standard of care for patients with ER+/HER2- breast cancer."

"The heart of the I-SPY TRIALs is to change how new breast cancer treatments are developed, to find treatments that are more personalized, effective, and less toxic, faster. We are excited to be partnering with Arvinas and investigating the potential positive benefits of vepdegestrant. Women need better and more tolerable options for extended endocrine therapy. We hope this will be one of them." said Dr. Laura Esserman, co-principal investigator of the I-SPY TRIAL and founder of Quantum Leap.

Arvinas will provide vepdegestrant and financial support to Quantum Leap for this investigational study. Quantum Leap is the sponsor of the I-SPY program, which includes 41 open sites. All I-SPY sites have the EOP program open.

About vepdegestrant (ARV-471)
Vepdegestrant is an investigational, orally-bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with early and locally advanced or metastatic ER positive/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Use of vepdegestrant in the ongoing and planned clinical trials will continue to monitor and evaluate patient safety and anti-tumor activity.

In preclinical studies, vepdegestrant demonstrated up to 97% ER degradation in tumor cells, induced tumor shrinkage when dosed as a single agent in multiple ER-driven xenograft models, and showed increased anti-tumor activity when compared to a standard of care agent, fulvestrant, both as a single agent and in combination with a CDK4/6 inhibitor. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will equally share worldwide development costs, commercialization expenses, and profits.