GDC-4198

Shows activity

Also known as:

RGT-419B RO7840734

Cancer types include:

breast cancer

HealthScout AI Analysis

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Overview

GDC-4198 (also known as RGT-419B; Roche code RO7840734) is an investigational, oral small‑molecule cyclin‑dependent kinase inhibitor being developed for hormone receptor–positive, HER2‑negative (HR+/HER2−) advanced or metastatic breast cancer, including disease that has progressed on prior CDK4/6 inhibitor plus endocrine therapy. Genentech (Roche) acquired Regor Therapeutics Group’s next‑generation CDK inhibitor portfolio, including RGT‑419B, in September 2024 and is sponsoring subsequent development as GDC‑4198/RO7840734. (prnewswire.com)

Mechanism of action

GDC‑4198/RGT‑419B is described as a next‑generation CDK inhibitor with high potency against CDK4, additional activity against CDK2, and relative selectivity versus CDK6. The profile aims to address resistance to approved CDK4/6 inhibitors and potentially reduce hematologic toxicity. (aacrjournals.org)

Efficacy

Early human data (Phase 1a, single‑agent dose‑escalation; interim analysis) in post‑menopausal patients with HR+/HER2− advanced/metastatic breast cancer previously treated with endocrine therapy and at least one CDK4/6 inhibitor reported: - Partial responses in 2 of 7 patients with measurable disease in the first three dose cohorts (25–150 mg once daily), for a 28.6% RECIST v1.1 PR rate; clinical benefit rate 44% at the June 30, 2023 cutoff. (aacrjournals.org)

Press materials summarizing the same study later noted 3 partial responses among 12 treated patients and that 6 patients remained on treatment for more than 24 weeks; these figures should be interpreted as preliminary and derived from company communications. (en.prnasia.com)

No randomized efficacy results are available as of October 7, 2025.

Safety

In the Phase 1a interim analysis, the most common treatment‑emergent adverse events (all causality) were nausea, decreased neutrophils/lymphocytes, and diarrhea. At the data cutoff, no grade ≥3 treatment‑related adverse events, no dose‑limiting toxicities, no ocular toxicity, and no discontinuations due to study drug were reported. (aacrjournals.org)

Company press summaries of the same dataset similarly stated no dose‑limiting toxicities and no discontinuations due to adverse events. (en.prnasia.com)

Clinical development status

First‑in‑human Phase 1 study (NCT05304962): RGT‑419B as monotherapy and in combination with endocrine therapy in HR+/HER2− advanced or metastatic breast cancer after prior CDK4/6 inhibitor; recruiting/active with sites in the United States. (cdek.pharmacy.purdue.edu)
Phase Ib/II study (GO46021; NCT07100106): GDC‑4198 alone and with giredestrant versus abemaciclib plus giredestrant in HR+/HER2− locally advanced/metastatic breast cancer post‑CDK4/6 inhibitor; first posted August 3, 2025; recruiting. Primary completion is estimated for July 31, 2030. (ichgcp.net)

Active trials using GDC-4198

Found 2 active trials using this drug:

A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor

Sponsor: Genentech, Inc. (industry) Phase: 1/2 Start date: Aug. 3, 2025

HealthScout AI summary: Adults with ER-positive, HER2-negative locally advanced/metastatic breast cancer who have progressed on prior CDK4/6 inhibitor plus endocrine therapy (ECOG 0–1) are enrolled to receive GDC-4198—an oral next-generation cyclin-dependent kinase inhibitor with potent CDK4 and additional CDK2 activity—alone or with the oral SERD giredestrant, and in Phase II are randomized to GDC-4198 + giredestrant (two dose levels) versus abemaciclib + giredestrant. Excludes visceral crisis requiring chemotherapy and prior chemotherapy for metastatic disease.

ClinicalTrials.gov ID: NCT07100106

First-in-Human, Escalating Oral Dose Study of RGT-419B Given Alone and With Endocrine Therapy in Subjects With Hormone Receptor Positive, Human Epidermal Growth Factor Receptor 2 Negative Advanced/Metastatic Breast Cancer

Sponsor: Regor Pharmaceuticals Inc. (industry) Phase: 1 Start date: March 4, 2022

HealthScout AI summary: Eligible patients are adults with estrogen receptor positive, HER2-negative, locally advanced or metastatic breast cancer who have progressed after prior CDK4/6 inhibitor and endocrine therapy, with limited prior lines of treatment in the metastatic setting. This study evaluates the investigational oral CDK4 inhibitor RGT-419B (selective for CDK4 with additional CDK2 activity and less CDK6 inhibition) given alone or with endocrine therapy.

ClinicalTrials.gov ID: NCT05304962