Arvinas and Pfizer Report Positive Phase 1b Data: Vepdegestrant Combined with Palbociclib Achieves 42% ORR in Heavily Pretreated ER+/HER2- Breast Cancer

▎WuXi

Edited by Kant Content Team

Arvinas and Pfizer announced positive data from the Phase 1b clinical trial of the investigational PROTAC protein degrader vepdegestrant (ARV-471) in combination with the CDK4/6 inhibitor Ibrance (palbociclib). The trial enrolled patients with locally advanced or metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer who had previously received a median of four lines of therapy. Interim results indicate,The overall response rate (ORR) for breast cancer patients receiving the combination therapy was 42%, with a median progression-free survival (PFS) of 11.1 months, demonstrating the potential of vepdegestrant combined with palbociclib in treating breast cancer.According to the press release, before more data is released and agreements with regulatory agencies are reached, Arvinas and Pfizer plan to expand the development scope of vepdegestrant, incorporating new combinations with CDK inhibitors into first-line and second-line treatment options.

Data from patients receiving vepdegestrant in combination with palbociclib are as follows:

The clinical benefit rate (CBR, defined as the proportion of patients with confirmed complete response, partial response, or stable disease for ≥24 weeks) was 63% (n=29/46, 95% CI: 47.5-76.8).; When using the recommended phase 3 trial dose (RP3D) of 200mg (n=21), the CBR was 67% (n=14/21, 95% CI: 43.0-85.4).With

ESR1

The CBR for mutant patients was 72% (n=21/29, 95% CI: 52.8-87.3).

; RP3D is 200 mg

At the time (n=14), the CBR was 79% (n=11/14, 95% CI: 49.2-95.3).

The objective response rate (ORR) was 42% (n=13/31, 95% CI: 24.5-60.9); RP3D was 200 mg.Time(n=15) had an ORR of 53% (95% CI: 26.6-78.7).With

The ORR for patients with ESR1 mutations was 47% (n=8/17, 95% CI: 23.0-72.2); the ORR at RP3D of 200 mg (n=10) was 60% (95% CI: 26.2-87.8).

The median progression-free survival for patients was 11.1 months (95% CI: 8.2-NE).; As of the data cutoff date, 22 progression events occurred among 46 patients across all dose groups. With

The PFS for patients with ESR1 mutations was 11.0 months (95% CI: 8.2-NE), and as of the data cutoff date, progression events occurred in 13 of 29 patients.

In the detection of circulating tumor DNA (ctDNA),With

Patients with ESR1 mutations (n=22) exhibited

The average decrease in ESR1 mutant allele fraction was -96.8% (range: -75.6% to -100%).

▲Arvinas' Pipeline in the Oncology Field (Image Source:Arvinas, Inc. Official Website）

The safety profile of the Vepdegestrant and palbociclib combination therapy can be managed by dose reduction and/or treatment interruption of palbociclib as per protocol. The main toxicity associated with this combination therapy is neutropenia.

ARV-471 is a PROTAC therapy that has gained widespread attention.As an oral PROTAC protein degrader that targets and degrades estrogen receptors, ARV-471 can degrade nearly all ER molecules within tumor cells.

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