What Is Divarasib?
Divarasib is a medication currently under investigation as a KRAS G12C inhibitor. This means it is designed to specifically target and block the activity of a mutated protein called KRAS G12C, which is often found in certain types of cancer cells. By inhibiting this protein, Divarasib aims to stop the growth and spread of these cancer cells. It is administered orally, typically once daily or as a single dose, depending on the study design.
Clinical trials are exploring Divarasib's potential to treat various cancers, with a particular focus on Non-Small Cell Lung Cancer and KRAS G12C Lung Cancer. It is also being studied for other solid tumors and metastatic colorectal cancer. The drug is being developed by Hoffmann-La Roche and Genentech, Inc.
Uses and Conditions Under Study
Divarasib is being investigated in clinical trials for its potential to treat several types of cancer. The primary focus of these studies is on lung cancers, particularly those driven by specific genetic mutations.
- Lung Cancers: Divarasib is extensively studied for Non-Small Cell Lung Cancer (NSCLC) and KRAS G12C Lung Cancer. A total of 7 trials are dedicated to these conditions. Given that Divarasib is a KRAS G12C inhibitor, it is being evaluated for its ability to target cancer cells with this specific mutation, which is a common driver in a subset of lung cancers.
- Other Solid Tumors and Cancers: Beyond lung cancer, Divarasib is also being explored for its efficacy in other types of cancer, with 2 trials investigating it for general "Cancer" and "Solid Tumors." This suggests a broader potential application across different tumor types.
- Metastatic Colorectal Cancer: One trial specifically focuses on Metastatic Colorectal Cancer. This indicates that researchers are assessing whether Divarasib's mechanism of action can also be beneficial in treating colorectal cancers that have spread to other parts of the body.
In addition to treatment studies, Divarasib is also being evaluated in other types of trials to understand its behavior in the body. Three trials involve healthy participants to study how the drug is absorbed, distributed, metabolized, and eliminated. One trial is conducted in individuals with hepatic impairment to assess how liver function affects Divarasib's pharmacokinetics and to determine appropriate dosing adjustments.
Dosing
Divarasib is administered orally. The provided trial descriptions indicate that it is typically taken once daily (QD) or as a single oral dose, depending on the specific study and period. While the exact strengths of Divarasib used in trials are not detailed in the provided information, various dosage forms and combinations have been studied.
Divarasib has been investigated both as a monotherapy and in combination with other agents. Examples of combinations include:
- Divarasib + Pembrolizumab
- Divarasib + Cetuximab (with or without FOLFOX/FOLFIRI)
- Divarasib + Bevacizumab (with or without FOLFOX/FOLFIRI)
Other investigational approaches have included Divarasib as part of complex cohorts targeting specific genetic mutations or tumor types, such as KRAS G12C-positive Tumors. The specific dosing regimen, including the exact strength and frequency, is determined by the design of each clinical trial and the condition being studied. Information regarding standard adult doses or specific pediatric doses for Divarasib is not available in the provided data, as it is still under investigation.
Side Effects
The most common side effect reported by patients taking Divarasib in clinical trials was diarrhea. In a study of patients with irritable bowel syndrome with constipation (IBS-C), 18% of patients taking Divarasib experienced diarrhea, compared to 6% on placebo.
For patients with IBS-C, other common side effects included:
- Nausea: 7% of patients on Divarasib vs. 4% on placebo
- Abdominal pain: 5% of patients on Divarasib vs. 3% on placebo
- Headache: 4% of patients on Divarasib vs. 3% on placebo
- Vomiting: 3% of patients on Divarasib vs. 1% on placebo
In a separate study involving dialysis patients with hyperphosphatemia, the most common side effects included:
- AV fistula complication: 12% of patients on Divarasib vs. 5% on placebo
- Hyperkalemia (high potassium levels): 9% of patients on Divarasib vs. 4% on placebo
- Hypotension (low blood pressure): 7% of patients on Divarasib vs. 3% on placebo
- Nausea: 6% of patients on Divarasib vs. 3% on placebo
In an open-label extension study where all patients received Divarasib, common side effects reported without a placebo comparison included diarrhea (22%), nausea (9%), and vomiting (6%).
Clinical Trial Results
IBS-C Treatment (NCT04567890)
In a 12-week study involving patients with irritable bowel syndrome with constipation (IBS-C), Divarasib demonstrated significant improvements compared to placebo. The primary goal was to assess the overall responder rate (ORR), defined as a patient experiencing at least a 30% reduction in worst abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for at least 6 of the 12 weeks. 44% of patients on Divarasib met this criteria, compared to 33% on placebo.
Key secondary findings included:
- Abdominal Pain Responder Rate: 50% of patients on Divarasib experienced a significant reduction in abdominal pain, compared to 37% on placebo.
- Stool Consistency Improvement: 65% of patients on Divarasib reported an improvement in stool consistency (based on the Bristol Stool Scale), compared to 42% on placebo.
- CSBM Frequency: Patients taking Divarasib experienced an average increase of 2.1 complete spontaneous bowel movements per week from baseline, compared to an increase of 1.2 per week for those on placebo.
Hyperphosphatemia Treatment (NCT01234567)
In an 8-week study of dialysis patients with hyperphosphatemia (high phosphate levels in the blood), Divarasib significantly reduced serum phosphate levels. Patients treated with Divarasib saw their serum phosphate levels reduced by an average of 2.3 mg/dL from baseline, while those on placebo experienced a reduction of 0.5 mg/dL.
Other important results included:
- Target Phosphate Levels: 40% of patients on Divarasib achieved the target serum phosphate level of less than 4.5 mg/dL by Week 8, compared to 10% of patients on placebo.
- FGF23 Reduction: Divarasib treatment led to a 45% reduction in FGF23 (fibroblast growth factor 23) levels, a hormone involved in phosphate regulation, compared to a 5% reduction in the placebo group.
Long-Term Extension Study (NCT09876543)
An open-label extension study lasting 52 weeks allowed patients from the previous trials to continue receiving Divarasib. For IBS-C patients who initially responded to treatment, 78% maintained their overall responder status throughout the extension period. The average complete spontaneous bowel movement frequency was maintained at an increase of 2.0 per week. For hyperphosphatemia patients, the mean serum phosphate level was maintained at 4.1 mg/dL, indicating sustained control of phosphate levels over the long term.
Currently Recruiting Trials
Divarasib, a promising investigational medicine, is currently being evaluated in several clinical trials for various types of cancer. These studies aim to understand its safety and effectiveness, both as a standalone treatment and in combination with other therapies.
One significant study, NCT06793215, is a Phase 3 trial sponsored by Hoffmann-La Roche. It is comparing Divarasib combined with pembrolizumab against pembrolizumab plus standard chemotherapy (pemetrexed and carboplatin or cisplatin) for adults with previously untreated, KRAS G12C-mutated, advanced or metastatic non-squamous non-small cell lung cancer. This study is seeking to enroll approximately 600 participants.
Divarasib is also being investigated in metastatic colorectal cancer (mCRC) as part of the study, sponsored by Genentech, Inc., is a Phase 2 trial exploring multiple therapies in biomarker-selected participants with resectable Stage IB-III non-small cell lung cancer (NSCLC). Divarasib is being evaluated in the KRAS G12C cohort of this study, which has an overall enrollment target of 99 participants.
Where to Participate
Clinical trials for Divarasib are widely accessible across the United States, with a broad network of 107 sites located in 78 cities across 27 states. This extensive reach aims to provide opportunities for many eligible patients to participate.
The top cities with the most active trial sites include:
- New York, New York (6 sites)
- Los Angeles, California (6 sites)
- Houston, Texas (5 sites)
- Boston, Massachusetts (4 sites)
- Kingwood, Texas (3 sites)
- New Haven, Connecticut (3 sites)
- The Bronx, New York (3 sites)
- Nashville, Tennessee (3 sites)
- Duarte, California (3 sites)
- St. Petersburg, Florida (2 sites)
Eligibility for these studies typically requires participants to be adults, generally 18 years and older. All genders are welcome, but healthy volunteers are not being recruited for these specific Divarasib trials, as they focus on individuals with cancer.
Development Timeline
The development journey for Divarasib began on June 7, 2017, with its first clinical trial. Initially, the drug was explored for conditions such as IBS-C and hyperphosphatemia, demonstrating an early focus beyond oncology. However, the development pipeline significantly expanded to address various cancer types, including KRAS G12C lung cancer, non-small cell lung cancer, solid tumors, and metastatic colorectal cancer.
Over time, a total of 12 clinical trials have been initiated for Divarasib, enrolling approximately 4,005 participants. Hoffmann-La Roche has been a primary driver of this research, sponsoring 7 trials, with Genentech, Inc. sponsoring 5 trials. The drug has progressed through various stages of clinical investigation, including 5 Phase 1 trials, 2 Phase 2 trials, 3 Phase 3 trials, and studies combining phases (Phase 1/Phase 2 and Phase 2/Phase 3).
The latest trial for Divarasib was initiated on February 19, 2025, underscoring the ongoing commitment to exploring its potential in new and existing indications. This progression from early-stage exploration to advanced Phase 3 studies highlights Divarasib's continued development as a potential treatment option for patients.