Item 7.01 Regulation FD Disclosure.
On December 10, 2021, Arvinas, Inc. (the “Company”) issued a press release announcing clinical program updates for its PROTAC® protein degrader ARV-471, including updated data. The Company will present the updates on a conference call and webcast on December 10, 2021. Copies of the press release and presentation are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K and are incorporated herein by reference.
The information in this Item 7.01, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 8.01 Other Events.
On December 10, 2021, the Company announced updated data, as of the data cut-off date of September 30, 2021, from the dose escalation portion of its Phase 1/2 clinical trial of ARV-471 in patients with locally advanced or metastatic ER+/HER2- breast cancer to be presented as a virtual spotlight poster session at the 2021 San Antonio Breast Cancer Symposium (SABCS).
The dose escalation portion of the Company’s Phase 1/2 clinical trial of ARV-471 is designed to assess safety, tolerability and pharmacokinetics (“PK”) of ARV-471 in patients with locally advanced or metastatic ER+/HER2- breast cancer, as well as measures of anti-tumor activity as secondary endpoints.
Enrollment
As of the data cut-off date, 60 adult patients with locally advanced or metastatic ER+/HER2- breast cancer were treated in the Phase 1 dose escalation portion of the study with total daily ARV-471 doses ranging from 30 mg to 700 mg. This patient group is heavily pretreated, with a median of four prior therapies. All patients were previously treated with cyclin-dependent kinase (“CDK”) 4/6 inhibitors; 80% of patients received prior fulvestrant; and 78% received prior chemotherapy.
Efficacy
Of 47 patients who were evaluable for clinical benefit (confirmed complete response, partial response, or stable disease ³ 24 weeks) the clinical benefit rate was 40%. As of the data cutoff date, 14 patients were continuing to receive study treatment, including two patients who had been on treatment for over 18 months. Three confirmed partial responses were observed among the 38 patients with baseline response evaluation criteria in solid tumors (RECIST) measurable disease and at least one on-treatment tumor assessment.
Safety
Patients were treated in the monotherapy escalation at total daily doses of 30 mg (n=3), 60 mg (n=3), 120 mg (n=7), 180/200 mg (n=11), 360 mg (n=15), 500 mg (n=17), and 700 mg was administered BID (300 mg in the morning / 400 mg in the evening) (n=4). A maximum tolerated dose was not reached and no dose limiting toxicities or Grade ³4 treatment-related adverse events (“TRAEs”) were observed. Of the 60 patients, 37% had Grade 1 TRAEs and 57% had Grade £2 TRAEs, and the most common TRAEs were nausea (29%), fatigue (20%), and vomiting (10%). No Grade 1 or 2 TRAEs led to discontinuation or dose reduction of ARV-471. Four patients experienced six Grade 3 TRAEs that were potentially related to ARV-471, including: headache lasting 1-day, single occurrence of asymptomatic increased amylase and lipase, nausea and asymptomatic QTc prolongation, and post-biopsy venous embolism. The patient with the venous embolism was the only Grade 3 patient who discontinued ARV-471 due to a TRAE, and the patient with Grade 3 nausea was the only patient with a dose reduction due to a TRAE (reduced from 500 mg to 400 mg daily).
ER Degradation
In paired biopsies from 14 patients across all doses up to 500 mg daily, robust ER degradation of up to 89% was observed, regardless of ESR1 mutation status. Median and mean ER degradation across dose levels were 67% and 64%, respectively.
