Item 7.01 Regulation FD Disclosure.
On May 29, 2020, Arvinas, Inc. (the “Company”) issued a press release announcing updated data from the dose escalation portion of its Phase 1/2 clinical trial ofARV-110 in men with metastatic castration-resistant prostate cancer (“mCRPC”). The Company will present the updated data on a conference call and webcast on May 29, 2020. Copies of the press release and presentation are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form8-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 May 29, 2020, the Company announced updated data from the dose escalation portion of its Phase 1/2 clinical trial ofARV-110 in men with mCRPC to be reported by study investigators at the 2020 American Society of Clinical Oncology (“ASCO”) Annual Meeting.
The dose escalation portion of the Company’s Phase 1/2 clinical trial ofARV-110 is designed to assess safety, tolerability and pharmacokinetics (“PK”) ofARV-110 in men with mCRPC who have progressed on standard of care therapies, as well as to identify a recommended Phase 2 dose. To date,ARV-110 has shown a favorable safety profile, and PK have been generally dose proportional, reaching exposures associated with tumor inhibition in preclinical models at 140 mg. In the data released today, the Company also shared evidence ofin-tumor androgen receptor (“AR”) reduction, the first demonstration of successful targeted protein degradation by a PROTAC protein degrader in humans.
ARV-110 has demonstrated evidence of activity at doses and in AR mutational backgrounds in which responses would be expected based on preclinical data. As of the April 20, 2020 datacut-off, 20 patients were evaluable for prostate-specific antigen (“PSA”) response, including 12 patients treated at 140 mg or higher. These 12 patients exclude one patient who received two weeks of therapy prior to discontinuing due to a rosuvastatin-related dose limiting toxicity.
Of the 12 patients treated at 140 mg and above, circulating tumor DNA analysis of five patients showed AR forms (L702H point mutations andAR-V7 splice variants) not degradable byARV-110 in preclinical studies. In the group of seven remaining patients who had degradable forms of AR (other AR point mutations, AR amplification and wildtype AR), two patients achieved confirmed PSA responses that remain ongoing with additionalfollow-up since the abstract was submitted for consideration by ASCO.
One of these patients had a 74% decline from baseline in PSA and remained without progression after 30 weeks, as of the datacut-off. This patient did not have measurable disease at baseline for assessment by Response Evaluation Criteria in Solid Tumors (“RECIST”), a standardized set of rules for response assessment based on tumor shrinkage. The second patient had both a deep PSA response (97% decline from baseline) and a confirmed RECIST response (80% decrease from baseline in tumor mass) and remains without progression after 18 weeks, as of the datacut-off. Both responses, which were in patients at the 140 mg dose, were achieved byARV-110 despite prior treatment with enzalutamide, abiraterone, chemotherapy and other therapies. Tumors from both patients have H875Y and T878A point mutations in AR, which are known to drive resistance to current standard of care treatments and have been degraded byARV-110 in preclinical studies. In addition to these two patients, PSA reductions were observed in other patients but did not meet a 50% reduction in PSA threshold at data cutoff, and four patients remain onARV-110 without radiographic progression for at least 20 weeks.
A potential drug-drug interaction betweenARV-110 and rosuvastatin (“ROS”) was identified during the trial. Of the 22 patients enrolled, two had concurrent use of ROS. One patient receiving 280 mgARV-110 experienced a Grade 4 dose-limiting toxicity (DLT) of elevated aspartate transaminase/alanine transaminase (“AST/ALT”) liver enzymes followed by acute renal failure. The second patient, receiving 70 mgARV-110, experienced a Grade 3 AST/ALT
