GDC-4198 + Giredestrant for Breast Cancer

Recruiting at 5 trial locations

Overseen By Reference Study ID Number: GO46021 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Genentech, Inc.

Must not be taking: Chemotherapy, Investigational therapies, others

Disqualifiers: Visceral spread, Poor venous access, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

285 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for individuals with certain types of advanced breast cancer. It aims to assess the safety and effectiveness of GDC-4198, an experimental treatment, when used alone or with another drug, giredestrant. The trial will also compare this new combination to a current treatment option that includes abemaciclib and giredestrant. Individuals with estrogen receptor-positive (ER+) and HER2-negative (HER2-) breast cancer, whose disease has progressed despite previous treatments, might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

You may need to stop taking certain cancer treatments before joining the trial. Specifically, you should not have taken any anti-cancer therapies within 28 days or certain oral endocrine therapies within 7 days before starting the study drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown promising safety results for the combination of GDC-4198 and giredestrant. Research indicates that giredestrant, when paired with another drug, significantly reduced the risk of disease progression. Patients who took GDC-4198 with giredestrant experienced a notable improvement in the duration their cancer did not worsen.

Regarding the combination of abemaciclib and giredestrant, earlier research shows it is generally safe. Studies found that patients tolerated this combination well, even those who had undergone many prior treatments. The combination of abemaciclib with hormone therapy also reduced the risk of death in patients with certain types of breast cancer.

These findings suggest that both combinations in the trial are generally well-tolerated, with no major safety concerns reported in the available data. However, as with any treatment, patients should discuss potential side effects with their doctors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they offer new ways to target the disease. Unlike standard treatments like chemotherapy and hormone therapies, GDC-4198 and giredestrant work by specifically modulating estrogen receptors, potentially offering a more precise approach. GDC-4198 is a novel agent that could enhance the effectiveness of hormone therapy by targeting cancer cells more directly. Additionally, the combination with abemaciclib, a well-known CDK4/6 inhibitor, could further inhibit cancer cell growth and division. These features may provide better outcomes with potentially fewer side effects, making these treatments a promising development in breast cancer care.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research shows that combining GDC-4198 and giredestrant may help treat ER+ (estrogen receptor-positive) and HER2- (HER2-negative) breast cancer. Early results suggest that patients with this type of cancer have experienced longer periods without progression. In this trial, participants in different arms will receive these combinations. Specifically, some participants will receive GDC-4198 and giredestrant, while others will receive abemaciclib and giredestrant. The combination of abemaciclib and giredestrant has also proven effective; studies showed that 63.8% of patients had a partial response, and 6.9% had a complete response after three months. Researchers continue to study these combinations to confirm their efficacy and safety. ^{6 7 8 9 10}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic ER+, HER2- breast cancer. Participants should not have received certain prior treatments and must be able to take oral medication. Specific health conditions and medications may exclude some people.

Inclusion Criteria

Measurable or non-measurable evaluable disease per RECIST v1.1

Life expectancy ≥ 6 months

My cancer progressed after treatment with CDK4/6 inhibitors and hormone therapy.

Exclusion Criteria

My cancer has spread to vital organs and needs urgent chemotherapy.

I have a condition or had surgery that affects how my body absorbs food.

I have had more than one treatment for my advanced cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase Ib

Evaluation of the safety and pharmacokinetics of GDC-4198 alone and in combination with giredestrant

Up to 36 months

Monthly visits (in-person)

Phase II

Comparison of the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant

Up to 36 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• GDC-4198
• Giredestrant

Trial Overview The study tests the safety of GDC-4198 alone and with giredestrant, comparing their effectiveness against abemaciclib combined with giredestrant. It includes an initial phase to assess safety and dosing, followed by a comparison phase.

How Is the Trial Designed?

Group I: Phase Ib: Dose-Finding Stage Experimental Treatment 2 Interventions

Participants will receive GDC-4198 as monotherapy and in combination with giredestrant, 30 milligrams (mg), orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group II: Phase II: Arm C Experimental Treatment 2 Interventions

Participants will receive abemaciclib, 150 mg twice daily, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group III: Phase II: Arm B Experimental Treatment 2 Interventions

Participants will receive GDC-4198, lower dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Group IV: Phase II: Arm A Experimental Treatment 2 Interventions

Participants will receive GDC-4198, higher dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Roche (China) Holding Ltd.

Collaborator

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07100106

NCT07100106 | A Study to Evaluate the Effect of GDC- ... The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1061

locally advanced/metastatic breast cancer (LA/mBC) ... Conclusions: The combinations of G + ATEZO, G + ATEZO + ABEMA, and G + ABEMA were tolerable, with no unexpected safety signals including no high ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT404708

A phase I/II study of G treatment (tx) combinations in ... This study provides the first data supporting the combinability of G with the CDK4/6is A and R, in addition to P as seen in prior studies.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12210239/

Abemaciclib treatment patterns and outcome in HR+/HER2 ... After three months of treatment, the rates of complete response (CR) and partial response (PR) as the best response were 6.9% and 63.8%, ...

5. onclive.com onclive.com/view/elacestrant-plus-abemaciclib-shows-efficacy-in-er-her2-advanced-or-metastatic-breast-cancer

Elacestrant Plus Abemaciclib Shows Efficacy in ER+/HER2 Elacestrant and abemaciclib combination showed an 18% objective response rate and 84% clinical benefit rate in ER-positive/HER2-negative breast ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04961996

NCT04961996 | A Study Evaluating the Efficacy and Safety ... This is a Phase III, global, randomized, open-label, multicenter, study evaluating the efficacy and safety of adjuvant giredestrant compared with endocrine ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.1061

Interim analyses (IA) of the giredestrant (G), G + ... This study provides the first data supporting the combinability of G with the CDK4/6is A and R, in addition to P as seen in prior studies.

8. esmoopen.com esmoopen.com/article/S2059-7029(24)00913-X/fulltext

158TiP Neoadjuvant abemaciclib and giredestrant trial in ... The first data on the combination of G and abemaciclib (A) showed a good safety profile with a 40% clinical benefit rate in heavily pre-treated patients (pts) ...

9. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12179-9

heredERA Breast Cancer: a phase III, randomized, open-label ... Preliminary data for giredestrant plus abemaciclib or ribociclib showed that the combinations were well tolerated, supporting the combinability ...

10. onclive.com onclive.com/view/abemaciclib-plus-endocrine-therapy-provides-os-benefit-in-hr-her2-negative-breast-cancer

Abemaciclib Plus Endocrine Therapy Provides OS Benefit ... Abemaciclib plus endocrine therapy reduced death risk by 15.8% in high-risk early breast cancer patients compared to endocrine therapy alone.