On January 9, 2023, the Company and Pfizer Inc. ("Pfizer") provided updated guidance related to the anticipated initiation of the VERITAC-3 first-line, metastatic estrogen receptor positive/HER2 negative (ER+/HER2-) breast cancer Phase 3 study of ARV-471 in combination with IBRANCE® (palbociclib).
In the most recent analysis of data from the ongoing Phase 1b combination study of ARV-471 with palbociclib, an increase in palbociclib exposure was observed relative to historical palbociclib pharmacokinetic data.
In light of the recent data analysis, the Company and Pfizer have proposed a modification to the planned VERITAC-3 Phase 3 study and requested a meeting with the U.S. Food and Drug Administration (the "FDA") to review the proposed update to the VERITAC-3 Phase 3 study protocol for ARV-471 in combination with palbociclib to determine the optimal dose of palbociclib as part of the trial design. In the event that the FDA agrees with the proposed amendment, the Company and Pfizer expect to initiate enrollment of the VERITAC-3 Phase 3 study in the second half of 2023. The Company and Pfizer expect to provide a regulatory update after meeting with the FDA.
In the most recent analysis of data from the ongoing Phase 1b study of ARV-471
in combination with palbociclib, the following were observed:
•An approximate increase of 50% in mean palbociclib exposure (i.e.,
pharmacokinetic area under the curve and Cmax) in the fed state was observed
relative to historical palbociclib pharmacokinetic data in the fasted state.
•Grade 3/4 neutropenia, a known dose-related adverse reaction associated with
palbociclib, was 76% for 200 mg ARV-471 with 125 mg palbociclib (n=21).
As per the U.S. Package Insert, (USPI) the starting dose of palbociclib for
patients with HR+/HER2- metastatic breast cancer is 125 mg. As per the
palbociclib USPI, a Grade ?3 decrease in neutrophil counts was reported in 66%
of patients receiving IBRANCE plus letrozole in Study 1 (PALOMA-2) and 66% of
patients receiving IBRANCE plus fulvestrant in Study 2 (PALOMA-3).
There was no increase in the rate of infection reported in the ARV-471 with
palbociclib Phase 1b investigation relative to the rates reported in the
registrational Phase 3 studies of palbociclib.
•The neutropenia events in the ARV-471 Phase 1b study were manageable with
standard dose reductions of palbociclib.
•In the arm combining palbociclib with 200 mg ARV-471, one of 21 patients
discontinued.
In addition to the above, the Company also provided the updated guidance set forth below related to its other programs. •VERITAC-2, a Phase 3 pivotal trial (First Subject First Visit) with ARV-471 as a second-line treatment in patients with ER+/HER2- metastatic breast cancer, is actively recruiting.
The Company initiated the TACTIVE-U, the Phase 1b trial with ARV-471 in
combination with ribociclib and abemaciclib, in two of the combination arms in
the fourth quarter of 2022.
•The Company expects to present data from the Phase 1b combination trial of
ARV-471 with palbociclib in the second quarter of 2023.
•The Company expects to initiate a Phase 3 trial with ARV-471 in the adjuvant
setting.
The Company expects to initiate a pivotal trial for bavdegalutamide (ARV-110)
for the treatment of men with metastatic castration-resistant prostate cancer in
the second half of 2023.
•The Company expects to report data from the Phase 1 dose escalation trial of
ARV-766 for the treatment of men with metastatic castration-resistant prostate
cancer in the second quarter of 2023.
The Company expects to submit an investigational new drug ("IND") application
or clinical trial application ("CTA") for its BCL6 PROTAC® degrader in the
second half of 2023.
•The Company expects to submit an IND or CTA for its PROTAC® LRRK2 degrader in
the second half of 2023.
•The Company expects to have two additional programs in IND-enabling studies by
the end of 2023.https://www.marketscreener.com/quote/stock/ARVINAS-INC-46353308/news/ARVINAS-INC-Regulation-FD-Disclosure-Other-Events-Financial-Statements-and-Exhibits-form-8-K-42691455/
