...the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for the investigation of vepdegestrant (ARV-471) for monotherapy in the treatment of adults with estrogen receptor (ER) positive/human growth epidermal growth factor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer previously treated with endocrine-based therapy.

With 12 months of additional follow-up from the first data report, durable clinical activity with vepdegestrant 200 mg QD was seen in heavily pretreated patients with ER+/HER2- advanced breast cancer, in addition to sustained reduction in circulating mutant ESR1 tumor DNA levels.

Clinical benefit rate (rate of confirmed complete or partial response [PR] or stable disease ≥24 wks) for evaluable pts (n=76) was 37% (95% CI: 26–49). Of 64 pts with baseline measurable disease, 6 had a confirmed and 4 an unconfirmed PR….Vepdegestrant continued to be well tolerated across all doses and showed clinical activity in heavily pretreated pts with ER+/HER2- advanced breast cancer...

CBR with ARV-471 200 mg QD was 37.1% (95% CI: 21–55) in all evaluable pts (n=35) and 47.4% (95% CI: 24–71)…CBR with ARV-471 200 mg QD was 37.1% (95% CI: 21–55) in all evaluable pts (n=35) and 47.4% (95% CI: 24–71)...After longer follow-up, ARV-471 200 mg QD continued to show clinical activity and was well tolerated in heavily pretreated pts with ER+/HER2- advanced breast cancer.

In VERITAC, ARV-471 monotherapy was administered at doses of 200 mg once daily (QD) or 500 mg QD to patients with ER+/HER2- locally advanced/metastatic breast cancer….CBR was 37.1% (95% CI: 21–55) in 35 evaluable patients treated at 200 mg QD and 38.9% (95% CI: 23– 57) in 36 evaluable patients treated at 500 mg QD. CBR in evaluable patients with mutant ESR1 in the 200 mg QD (n=19) and 500 mg QD (n=22) cohorts was 47.4% (95% CI: 24–71) and 54.5% (95% CI: 32–76), respectively....In the phase 2 VERITAC expansion cohorts of patients with ER+/HER2- locally advanced/metastatic breast cancer and prior CDK4/6 inhibitor treatment, ARV-471 monotherapy showed evidence of clinical activity based on CBR, which was further enhanced in the subgroup with ESR1 mutations.

As of the data cut-off date of November 11, 2020, 21 adult patients with locally advanced or metastatic ER+/HER2- breast cancer completed at least one treatment cycle with ARV-471 (orally, once-daily) in the Phase 1 clinical trial...one patient in the ARV-471 trial had a confirmed PR with a 51% reduction in target lesion size as assessed by RECIST. Two additional patients had unconfirmed PRs and one additional patient demonstrated stable disease with >50% target lesion shrinkage…Five of 12 patients (42%) achieved CBR (CBR defined as PRs + complete responses + stable disease at 6 months).