| Item 7.01 | Regulation FD Disclosure. |
On December 14, 2020, Arvinas, Inc. (the “Company”) issued a press release announcing clinical program updates for its PROTAC® protein degraders ARV-471 and ARV-110, including updated data. The Company will present the updates on a conference call and webcast on December 14, 2020. 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.
ARV-471 Clinical Update
On December 14, 2020, the Company announced updated interim data from the dose escalation portion of its ongoing Phase 1/2 clinical trial of ARV-471 in patients with locally advanced or metastatic ER+/HER2- breast cancer. The dose escalation portion of the Company’s Phase 1/2 clinical trial of ARV-471 is designed to assess the safety, tolerability and pharmacokinetics (“PK”) of ARV-471 and also includes measures of anti-tumor activity as secondary endpoints.
As of the data cut-off date of November 11, 2020, 21 adult patients with locally advanced or metastatic ER+/HER2- breast cancer were dosed with ARV-471 (orally, once-daily) in the Phase 1 clinical trial. 100% of these patients were previously treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor, 71% of patients also received prior fulvestrant, and 23% of patients were also pretreated with investigational selective estrogen receptor degraders (“SERDs”). Overall, patients had a median of five prior therapies.
One patient in the ARV-471 trial had a confirmed partial response, with a 51% reduction in target lesion size as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), a standardized set of rules for response assessment based on tumor shrinkage. In addition to the confirmed partial response, two additional patients had unconfirmed partial responses and one additional patient demonstrated stable disease with greater than 50% target lesion shrinkage. For a clinical benefit rate (“CBR”) evaluation, 12 patients had sufficient follow-up to be included. Five of 12 patients (42%) achieved CBR. CBR is defined to include partial responses, complete responses and stable disease at 6 months. Three of these five patients had previously received fulvestrant, and another was treated with two investigational SERDs.
ARV-471 has also been well tolerated at all dose levels, as of the data cut-off date. The most common treatment-related Grade 1-2 adverse events were nausea (24%), arthralgia (19%), fatigue (19%), and decreased appetite (14%). None of these led to discontinuation or dose reduction of ARV-471. No patients reported treatment-related Grade 3 of 4 adverse events, and no dose-limiting toxicities have been reported. A maximum tolerated dose has not been reached and dose escalation continues.
The plasma exposures of ARV-471 have been dose proportional up to and including 360 mg orally once daily and have substantially exceeded the Company’s predicted thresholds of efficacy based on preclinical studies. The estimated half-life of ARV-471 is 28 hours, supporting a once-daily schedule of administration. Analysis of five paired tumor biopsies at doses up to 120 mg provide compelling proof of mechanism for ARV-471. At those doses, the Company has observed ER degradation up to 90% (average of 62%).
The Company believes that the interim data from its ongoing clinical trial compares favorably to previously reported Phase 1 clinical trial results of other SERDs with respect to tolerability, ER degradation and efficacy signals.
