Pfizer has terminated the Phase 1 study of its SHP2 inhibitor PF-07284892, marking the latest setback for the SHP2 target in cancer treatment, following multiple pharmaceutical companies encountering difficulties with this target.

According to the trial registry update, Pfizer ended this study "due to strategic reasons, rather than major safety issues, inefficacy, or requests from any regulatory authority."

Pfizer acquired the drug in its $11.4 billion acquisition of Array BioPharma in 2019.

SHP2, fully known as the Src Homology Region 2 Domain-Containing Phosphatase, is a key signaling node and regulator that promotes cancer cell survival and growth through the RAS pathway and plays a critical role in how cancer cells develop resistance to targeted therapies.

SHP2-related signaling pathways (Source: Internet)

PF-07284892 is an SHP2 inhibitor designed to overcome bypass signaling-mediated resistance and has demonstrated activity in various tumor models.

Chemical Structure of PF-07284892 (Source: MCE)

PF-07284892 was presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, including studies as a monotherapy and in combination with other targeted therapies for drug-resistant solid tumors. Partial responses (PR) were observed in five patients when PF-07284892 was combined with lorlatinib, binimetinib, or cetuximab.

Despite Pfizer's Decision to Halt Research on PF-07284892, Positive Results from Other Companies in the SHP2 Inhibitor Field Bring New Hope for This Target. For Example, The Combination of JAB-3312 from Jacobi and Goletrectinib (KRAS G12C Inhibitor) Showed Promising Results in Phase I/IIa Clinical Trials, with an Objective Response Rate as High as 86.7% in a Small Sample Size of 15 Patients, Demonstrating Significant Advantages Compared to Existing Standard Therapies. This Provides a New Perspective for the Development of Numerous SHP2 Inhibitors.

SHP2 Inhibitors Under Research (Source: Asymchem Pharma News)

Summary:

Since 2022, Sanofi, AbbVie, Roche, BMS, and today’s Pfizer have all returned the star target SHP2 inhibitor to MNC for various "strategic and commercial" reasons. Currently, the fastest progressing SHP2 inhibitor globally is JAB-3068 from Jacobi, which is in Phase III development.

First-in-class is difficult, more difficult than ascending to the sky!

Reference: Pfizer

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