Itraconazole and Divarasib Interaction Study

Overseen By Reference Study ID Number: GP45714 https://forpatients.roche.com/

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Disqualifiers: Metabolic, Hepatic, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the drug Itraconazole affects the body's processing of another drug, Divarasib, in healthy individuals. Participants will take Itraconazole for a set period, followed by Divarasib, to observe their interaction and check for any side effects. The trial seeks individuals without long-term health issues, no medication allergies, and a healthy body mass index (BMI) between 18 and 32. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Previous studies have shown Divarasib to be generally safe. This medication targets a specific change in cancer cells. Most patients have tolerated it well, and it has proven safe for long-term use in some cancer treatments.

Itraconazole, used to treat fungal infections, has been available for a long time. However, it can sometimes cause serious effects when combined with other drugs, so monitoring these interactions is important.

This trial specifically studies how Divarasib and Itraconazole work together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Divarasib and Itraconazole because they offer a novel approach to treatment. Unlike other treatments, Divarasib specifically targets the KRAS G12C mutation, which is a common driver in several cancers but is challenging to treat with existing therapies like chemotherapy or immunotherapy. Itraconazole, typically an antifungal, is being explored here for its potential to enhance the effectiveness of Divarasib by affecting how the drug is processed in the body. This combination could lead to more efficient targeting of cancer cells and potentially improve patient outcomes.

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

Research has shown that Divarasib is a promising treatment for certain cancers. It targets a specific change in cancer cells called KRAS G12C, often found in some lung and colon cancers. Studies have demonstrated that Divarasib has led to positive results in patients, especially when combined with other treatments. In this trial, participants in Treatment A will receive a single oral dose of Divarasib. Meanwhile, Itraconazole, a well-known antifungal medication used to treat infections, is also being studied for its effects on other drugs, like Divarasib. Participants in Treatment B will receive Itraconazole along with Divarasib to examine how Itraconazole might alter the way Divarasib works in the body. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for healthy individuals who can participate in a study to understand how Itraconazole affects the body's handling of another drug, Divarasib. Specific eligibility criteria are not provided.

Inclusion Criteria

My BMI is between 18.0 and 32.0.

I cannot become pregnant or get someone pregnant.

Exclusion Criteria

History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the investigator

I have difficulty with blood draws or IV insertions due to poor vein access.

I have no major health issues like heart, kidney, liver diseases, or severe allergies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment Period A

Participants receive a single oral dose of Divarasib on Day 1

1 day

1 visit (in-person)

Treatment Period B

Participants receive Itraconazole BID on Day 1 and QD from Day 2 to Day 13, with Divarasib on Day 5

13 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Divarasib
• Itraconazole

Trial Overview The study is testing how taking Itraconazole, an antifungal medication, influences the levels and effects of Divarasib, a potential new treatment being tested in healthy participants over two different periods.

How Is the Trial Designed?

Group I: Treatment B Experimental Treatment 2 Interventions

Participants will receive Itraconazole twice a day (BID) on Day 1 and once a day (QD) from Day 2 to Day 13. Participants will receive Divarasib in combination with Itraconazole on Day 5.

Group II: Treatment A Experimental Treatment 1 Intervention

Participants will receive a single oral dose of Divarasib on Day 1.

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

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2303810

Single-Agent Divarasib (GDC-6036) in Solid Tumors with a ... The data we report here are from an ongoing phase 1, open-label, multicenter, dose-escalation, and dose-expansion study of divarasib as a single ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04449874

NCT04449874 | A Study to Evaluate the Safety, ... This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11111488/

Divarasib in the Evolving Landscape of KRAS G12C Inhibitors ... Divarasib is a potent and selective KRAS G12C inhibitor. Early results show promising efficacy and safety of divarasib. Divarasib may have ...

4. nature.com nature.com/articles/s41591-023-02696-8

Divarasib plus cetuximab in KRAS G12C-positive ... Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg.

5. roche.com roche.com/investors/updates/inv-update-2023-04-18

Roche presents positive phase Ib data at AACR 2023 ... In the phase Ib GO42144 study, divarasib in combination with cetuximab, an anti-EGFR therapy, led to a confirmed overall response in 62% of ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40632992/

Single-Agent Divarasib in Patients With KRAS G12C- ... With extended follow-up, divarasib demonstrated long-term safety and antitumor activity in patients with advanced KRAS G12C-positive NSCLC.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00040

Single-Agent Divarasib in Patients With <i>KRAS G12C</i> Divarasib (GDC-6036), an oral, highly potent and selective next-generation KRAS G12C inhibitor, has demonstrated a manageable safety profile and promising ...

8. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_2/CT022/761573/Abstract-CT022-Divarasib-plus-migoprotafib

Divarasib plus migoprotafib combination treatment in patients ... Divarasib in combination with migoprotafib demonstrated an acceptable safety profile and preliminary clinical activity in patients with KRAS ...