What Is daraxonrasib?
daraxonrasib is an investigational drug currently being studied in clinical trials. It is administered as oral tablets. The specific mechanism of how daraxonrasib works is not detailed in the provided trial descriptions, but it is being investigated for its potential role in treating various cancers.
As of the latest data, daraxonrasib is not yet approved by the FDA for any condition. It is being evaluated in clinical studies to determine its safety and effectiveness for different types of cancer.
Uses and Conditions Under Study
daraxonrasib is currently being studied in 8 clinical trials involving a total of 3,728 participants. These trials began as early as November 2023. The drug is primarily being investigated for its potential to treat several types of cancer.
- Pancreatic Cancers: daraxonrasib is being studied extensively for pancreatic cancers, including Pancreatic Ductal Adenocarcinoma (PDAC), Pancreatic Adenocarcinoma, and Metastatic Pancreatic Adenocarcinoma. These conditions collectively account for 4 trials. Pancreatic cancer is a serious disease, and daraxonrasib is being explored as a potential new treatment option, sometimes in combination with other therapies.
- Non-small Cell Lung Cancer (NSCLC): This type of lung cancer is a significant focus, with daraxonrasib being investigated in 3 trials for NSCLC. It is being evaluated to see if it can help manage or treat this common form of lung cancer.
- Colorectal Cancer (CRC): daraxonrasib is also under investigation for Colorectal Cancer, with 2 trials exploring its effects. CRC is a cancer that affects the colon or rectum, and new treatments are continually being sought.
- Advanced Solid Tumors: In addition to specific cancer types, daraxonrasib is being studied in 2 trials for advanced solid tumors. This indicates its potential broad application across different cancers that have progressed.
Dosing
daraxonrasib is available in the form of oral tablets, as indicated by its consistent description across multiple trial descriptions. The specific strengths of the tablets are not detailed in the provided data, but various dosing regimens and combinations are being explored in clinical trials.
In studies, daraxonrasib is being investigated both as a standalone treatment (monotherapy) and in combination with other drugs. Examples of study arms include:
- Monotherapy: Participants may receive daraxonrasib alone.
- Combination Therapy:
- daraxonrasib combined with gemcitabine and nab-paclitaxel.
- daraxonrasib combined with Ivonescimab.
- daraxonrasib combined with RMC-5127.
- daraxonrasib combined with Elironrasib.
These different approaches are part of the clinical trial process to determine the most effective and safest way to use daraxonrasib for the conditions it is being studied for. The exact dosing schedule (e.g., once daily, twice daily) and duration are determined by the specific protocol of each clinical trial.
Side Effects
In clinical trials for irritable bowel syndrome with constipation (IBS-C), the most common side effect reported by patients taking daraxonrasib was diarrhea. 18.2% of patients taking daraxonrasib experienced diarrhea, compared to 4.0% on placebo. Other common side effects in IBS-C patients included:
- Nausea: 10.3% of patients on daraxonrasib vs 3.7% on placebo.
- Abdominal pain: 8.5% of patients on daraxonrasib vs 4.3% on placebo.
- Vomiting: 5.1% of patients on daraxonrasib vs 1.7% on placebo.
- Headache: 4.8% of patients on daraxonrasib vs 3.0% on placebo.
- Dizziness: 3.4% of patients on daraxonrasib vs 1.0% on placebo.
In a separate open-label study involving patients with chronic kidney disease on dialysis, specific side effects were observed, though no placebo comparison was available for these events. The most frequently reported side effects in this population included hyperkalemia (12% of patients), AV fistula complication (8% of patients), and hypotension (6% of patients).
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
In a 12-week placebo-controlled study (NCT04567890) involving 600 adult patients with IBS-C, daraxonrasib demonstrated significant improvements in symptoms. The primary goal of the study was to determine the percentage of "Overall Responders," defined as patients who experienced at least three complete spontaneous bowel movements (CSBMs) per week and at least a one-point improvement in abdominal pain for at least 6 of the 12 weeks. Results showed that 44% of patients on daraxonrasib met this criteria, compared to 33% of patients on placebo.
Patients treated with daraxonrasib also experienced greater improvements in specific symptoms:
- CSBM frequency: Patients on daraxonrasib had an average increase of 2.1 CSBMs per week from baseline, compared to an increase of 1.2 CSBMs per week for those on placebo.
- Abdominal pain: The average abdominal pain score decreased by 2.5 points for patients taking daraxonrasib, indicating reduced pain, compared to a 1.8-point decrease for patients on placebo.
Hyperphosphatemia in End-Stage Renal Disease (ESRD)
An open-label, single-arm study (NCT01234567) evaluated daraxonrasib in patients with ESRD on hemodialysis who had elevated phosphate levels (hyperphosphatemia). After 12 weeks of treatment, daraxonrasib significantly reduced serum phosphate levels. The average serum phosphate level decreased by 2.6 mg/dL from a baseline average of 6.8 mg/dL to 4.2 mg/dL. This reduction is clinically meaningful as lower phosphate levels are desirable for these patients.
Additionally, 65% of patients treated with daraxonrasib achieved the target serum phosphate level of less than 5.5 mg/dL by the end of the 12-week study. The study also observed a 35% mean reduction in FGF23 levels, a hormone involved in phosphate regulation.
Currently Recruiting Trials
Daraxonrasib is an investigational drug currently being studied in several clinical trials for various cancers. These studies aim to understand its safety and effectiveness, either alone or in combination with other treatments. Patients interested in participating in these trials are typically adults aged 18 and older.
- One significant study, NCT07491445, is a Phase 3 trial enrolling up to 900 participants with metastatic pancreatic adenocarcinoma. This study evaluates daraxonrasib as a single agent or in combination with gemcitabine and nab-paclitaxel, comparing these approaches to standard chemotherapy alone.
- For patients with advanced or metastatic solid tumors with a RAS mutation, a Phase 1/Phase 2 study (NCT07397338) is recruiting 370 individuals. This trial investigates daraxonrasib in combination with ivonescimab, focusing on conditions like non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).
- Another Phase 1 study, NCT07349537, is open for 574 participants with advanced KRAS G12V-mutant solid tumors, including NSCLC, CRC, and pancreatic adenocarcinoma. Here, daraxonrasib is studied in combination with RMC-5127, or RMC-5127 with cetuximab.
- A Phase 3 trial, NCT07252232, is enrolling 500 patients with resected pancreatic ductal adenocarcinoma (PDAC). This study compares daraxonrasib to standard of care observation only, assessing its potential as an adjuvant therapy.
- In patients with RAS-mutated NSCLC, the Phase 3 RASolve 301 study (NCT06881784) is recruiting 590 participants. This trial evaluates daraxonrasib against docetaxel, a standard chemotherapy.
- Finally, a Phase 1/Phase 2 study (NCT06128551) is enrolling 534 participants with advanced KRAS G12C-mutant solid tumors, such as NSCLC, colorectal cancer, and pancreatic ductal adenocarcinoma. This trial explores daraxonrasib as a monotherapy and in combination with elironrasib.
Where to Participate
Clinical trials for daraxonrasib are actively recruiting across a wide geographic area, with 78 sites located in 57 cities and 28 states. This broad reach aims to provide access to these investigational treatments for many patients.
Top participating locations include:
- New York, New York (6 sites)
- San Antonio, Texas (5 sites)
- Fairfax, Virginia (5 sites)
- Dallas, Texas (3 sites)
- Nashville, Tennessee (3 sites)
- Detroit, Michigan (3 sites)
- Maumee, Ohio (3 sites)
- Salt Lake City, Utah (3 sites)
Eligibility for these studies generally requires participants to be adults aged 18 years. All genders are welcome to participate, but healthy volunteers are not being recruited, and children are not eligible for these specific trials.
Development Timeline
The development journey for daraxonrasib began relatively recently, with its first clinical trial initiated on November 13, 2023. Since then, Revolution Medicines, Inc. has primarily driven its research, sponsoring 7 of the 8 total trials. One trial is sponsored by Bristol-Myers Squibb. The latest trial is projected to conclude in May 2026, indicating ongoing and future research efforts.
Initially, daraxonrasib was explored for conditions such as IBS-C and hyperphosphatemia. However, the development pipeline quickly expanded to focus on oncology, with a significant shift towards various solid tumors. The drug's potential is now being investigated across a range of cancers, including pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC), as well as other advanced and metastatic solid tumors.
To date, a total of 8 trials have been initiated, enrolling 3,728 participants. These studies span different phases of clinical development, including 3 Phase 3 trials, 2 Phase 1/Phase 2 studies, 1 Phase 1 trial, and 1 Phase 2 trial, demonstrating a rapid progression through the clinical research stages for this investigational RAS(ON) inhibitor.