Sotorasib Clinical Trials

What Is Sotorasib?

Sotorasib is a drug being investigated for its potential in treating various cancers. It functions as a KRAS G12C inhibitor, meaning it targets a specific mutation in the KRAS gene, which is often found in certain types of tumors. By blocking the activity of this mutated protein, sotorasib aims to stop or slow cancer cell growth.

Currently, sotorasib is being studied in 50 clinical trials involving a total of 8,889 participants. The first trial began on July 26, 2018, and the latest is projected to conclude on January 6, 2026. While it is primarily being investigated for Non-Small Cell Lung Cancer, studies also explore its use in other advanced solid tumors and metastatic colorectal cancer.

Sotorasib is typically administered orally as a tablet. Some trials involve sotorasib as a monotherapy, while others combine it with other treatments like chemotherapy regimens or other targeted therapies.

Uses and Conditions Under Study

Sotorasib is primarily under investigation for its role in treating various cancers, particularly those with a specific genetic mutation. Clinical trials for sotorasib have enrolled a total of 8,889 participants across 50 studies.

• Non-Small Cell Lung Cancer (NSCLC): This is the most studied condition for sotorasib, with a total of 21 trials focusing on different stages and types of lung cancer, including Stage III and Stage IV Lung Cancer AJCC v8, and Metastatic Lung Non-Small Cell Carcinoma. Sotorasib targets the KRAS G12C mutation, which is often found in NSCLC, aiming to inhibit tumor growth.
• KRAS P.G12C Mutation: This specific genetic mutation is a key target for sotorasib. Three trials are specifically dedicated to participants with this mutation, regardless of the cancer type, highlighting sotorasib's targeted mechanism of action.
• Advanced Solid Tumors: Sotorasib is also being explored for its potential in a broader range of advanced solid tumors, with 3 trials investigating its efficacy in these diverse cancer types. This suggests its mechanism might be beneficial across different cancers that share similar genetic drivers.
• Metastatic Colorectal Cancer: Two trials are studying sotorasib in patients with metastatic colorectal cancer. This condition often presents challenges in treatment, and sotorasib's targeted approach could offer a new therapeutic option.
• Healthy Participants: Four trials involve healthy participants. These studies typically aim to understand how sotorasib is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics) and to assess its safety profile in individuals without the target disease.

One trial summary also mentions that Venous Thromboembolic Events (VTEs) are common in lung cancer patients, often requiring anticoagulant treatment. While not a direct use of sotorasib, this context highlights a common comorbidity in the patient population being studied.

Dosing

Sotorasib is primarily administered orally as a tablet. Clinical trials have investigated various dosing regimens, both as a single agent and in combination with other therapies.

The most frequently studied daily dose of sotorasib is 960 mg. This dose has been administered orally once daily (QD) for periods such as 4 weeks (28 days), or continuously until disease progression or unacceptable toxicity. For instance, one study combined sotorasib 960 mg QD with panitumumab.

Another dose strength under investigation is 240 mg daily. This lower dose has also been studied in combination with panitumumab, allowing researchers to evaluate different dose-response profiles and potential side effects.

Sotorasib has been studied in various combinations, including with first-line chemotherapy regimens like gemcitabine/nab-paclitaxel (gem/nab-P) or mFOLFIRINOX, as well as with other targeted agents such as panitumumab, pembrolizumab, trametinib, and carboplatin/pemetrexed. Some trials also explore sotorasib in combination with drugs like omeprazole or rosuvastatin to understand potential drug interactions.

The specific dosing schedule and duration of treatment can vary depending on the trial design, the condition being treated, and whether sotorasib is used as a monotherapy or in combination.

Side Effects

In a study (NCT05054725) evaluating Sotorasib in combination with RMC-4630 for non-small cell lung cancer, all participants in the RMC-4630 200 mg arm experienced at least one treatment-emergent adverse event (TEAE). Specifically, 43 out of 43 participants in this arm reported TEAEs. In the RMC-4630 140 mg arm, 4 out of 4 participants experienced TEAEs. The specific nature and frequency of individual side effects were not detailed in the provided data for this study.

Other studies focused on how Sotorasib is processed in the body, and reported overall occurrences of TEAEs:

• In a study (NCT04887064) involving healthy participants and those with liver impairment, 1 participant with normal liver function, 2 participants with moderate liver impairment, and 1 participant with severe liver impairment experienced one or more TEAEs.
• A study (NCT05048784) comparing different Sotorasib tablet formulations in healthy participants reported TEAEs in 8 participants for Treatment A, 10 participants for Treatment B, and 0 participants for Treatment C.
• No participants reported any TEAEs in a study (NCT05045638) investigating the interaction between Sotorasib and rosuvastatin in healthy participants.

Clinically significant changes in ECGs or vital signs were not observed in the combination study (NCT05054725). Some participants in this study did experience clinically significant changes in laboratory tests, with counts ranging from 1 to 5 participants across different treatment groups and types of changes.

Clinical Trial Results

Pharmacokinetics in Hepatic Impairment

A study (NCT04887064) investigated how Sotorasib is processed in the body of healthy individuals and those with varying degrees of liver impairment. The total exposure to Sotorasib (measured by AUCinf) was 29,000 h*ng/mL in participants with normal liver function, 21,700 h*ng/mL in those with moderate impairment, and 30,100 h*ng/mL in those with severe impairment. However, the unbound (active) form of Sotorasib showed different trends: unbound AUCinf was 742 h*ng/mL in normal function, increasing to 1,340 h*ng/mL in moderate impairment, and significantly higher at 4,680 h*ng/mL in severe impairment. Similarly, the maximum unbound concentration (Cmax,u) was 183 ng/mL in normal function, 400 ng/mL in moderate impairment, and 1,220 ng/mL in severe impairment. This indicates that patients with liver impairment, especially severe, may have higher levels of the active drug in their system due to reduced clearance (from 1,290 L/h in normal function to 205 L/h in severe impairment).

Drug-Drug Interaction with Rosuvastatin

In a study (NCT05045638) examining the coadministration of Sotorasib with rosuvastatin in healthy participants, Sotorasib increased the exposure to rosuvastatin. The total exposure (AUCinf) to rosuvastatin increased by approximately 34% (from 36.20 h*ng/mL when given alone to 48.40 h*ng/mL when given with Sotorasib). The maximum concentration (Cmax) of rosu

Currently Recruiting Trials

For patients interested in participating in clinical research, several studies are actively recruiting to investigate Sotorasib, a targeted therapy for cancers with a specific KRAS G12C mutation. These trials explore Sotorasib as a standalone treatment or in combination with other therapies across various advanced solid tumors.

One notable study, NCT07012031, is a Phase 1/2 trial sponsored by the National Cancer Institute. It is evaluating the safety and effectiveness of Sotorasib when combined with trastuzumab deruxtecan for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) that has a KRAS G12C mutation. This trial aims to enroll 37 participants.

Amgen is sponsoring two significant trials. NCT07172919 is a Phase 2 rollover study assessing the safety and tolerability of continuing Sotorasib, with or without panitumumab, in 14 participants with advanced solid tumors who are already benefiting from Amgen-sponsored protocols. Another Amgen-sponsored study, NCT06252649, is a Phase 3 trial for 450 treatment-naïve participants with metastatic colorectal cancer (mCRC) with a KRAS p.G12C mutation. It compares Sotorasib plus panitumumab and FOLFIRI against FOLFIRI with or without bevacizumab-awwb. Additionally, NCT05920356, also sponsored by Amgen, is a large Phase 3 trial, CodeBreaK 202, enrolling 750 participants. It compares Sotorasib combined with platinum doublet chemotherapy against pembrolizumab with platinum doublet chemotherapy as a front-line therapy for advanced NSCLC.

Several trials are investigating Sotorasib in combination with novel agents. NCT06804824, a Phase 1 study by Vividion Therapeutics, Inc., is a first-in-human trial for VVD-159642, which includes a cohort evaluating its combination with Sotorasib in advanced solid tumors, targeting 220 participants. Effector Therapeutics' Phase 1/2 study, NCT04092673, is exploring eFT226, with one cohort specifically combining it with Sotorasib for NSCLC, with an enrollment goal of 30 participants. NYU Langone Health is conducting NCT05815173, a Phase 1 study of ladarixin with Sotorasib in 40 participants with advanced KRAS G12C mutant NSCLC. City of Hope Medical Center's Phase 1 trial, NCT06249282, is testing carfilzomib in combination with Sotorasib for advanced or metastatic NSCLC with a KRAS G12C mutation, enrolling 15 patients.

For patients with brain tumors, Memorial Sloan Kettering Cancer Center is sponsoring NCT06807619, a Phase 1 study to assess how effectively Sotorasib penetrates KRAS G12C+ brain tumors and its safety and efficacy in 16 participants undergoing surgical resection.

The National Cancer Institute is also running NCT05638295, a Phase 2 ComboMATCH treatment trial, testing Sotorasib with or without panitumumab in 105 patients with KRAS G12C mutant solid tumors. This is part of a broader screening trial, NCT05564377, which is a Phase 2 ComboMATCH screening trial for 2900 participants with locally advanced or advanced solid tumors, directing patients to appropriate targeted therapy arms, including those involving Sotorasib.

Other trials include NCT06582771, a Phase 2 study by Memorial Sloan Kettering Cancer Center, investigating Sotorasib in 39 participants with advanced NSCLC with a KRAS G12C mutation who have not received prior treatment for advanced disease. Gustave Roussy, Cancer Campus, Grand Paris is conducting NCT05631249, a Phase 2 study of Sotorasib in 40 previously treated participants with locally advanced or metastatic NSCLC with a mutated KRAS p.G12C. Fundación GECP's Phase 2 trial, NCT05398094, evaluates Sotorasib for 19 participants with unresectable Stage III NSCLC with a KRAS p.G12C mutation who are ineligible for chemo-radiotherapy.

Finally, NCT05845450 is a Phase 2 UNICORN umbrella trial by Gruppo Oncologico del Nord-Ovest, enrolling 197 participants with resectable colorectal cancer. This study includes a cohort for KRAS G12C mutated tumors, where Sotorasib may be investigated as a pre-operative targeted treatment. NCT06333951, a Phase 1 master protocol by Amgen, is studying anvumetostat in combination with other therapies for advanced thoracic tumors, including a subprotocol for NSCLC with KRAS G12C mutation, aiming for 500 participants. An observational study, NCT06532149, is also recruiting 80 male participants with lung cancer to assess quality of life aspects like erectile dysfunction in those receiving new-generation anticancer treatments, which may include Sotorasib.

Where to Participate

Clinical trials for Sotorasib are widely accessible across the United States, with studies recruiting in 46 states. There are currently 583 sites across 386 cities offering opportunities for participation.

The top cities with the most recruiting sites include:

• New York, New York (13 sites)
• Columbus, Ohio (12 sites)
• Chicago, Illinois (11 sites)
• Nashville, Tennessee (9 sites)
• Las Vegas, Nevada (9 sites)
• St Louis, Missouri (9 sites)
• Houston, Texas (9 sites)
• Greenville, South Carolina (9 sites)
• Flint, Michigan (8 sites)
• Los Angeles, California (8 sites)

General eligibility for these trials includes individuals aged 18 to 100 years, of all genders. Most studies are designed for patients with specific medical conditions, meaning healthy volunteers are not typically eligible to participate. Some trials may also include children, depending on the specific study criteria.

Development Timeline

The journey of Sotorasib in clinical development began with its first trial on July 26, 2018. Since then, the research pipeline has expanded significantly, with the latest trial projected to conclude on January 6, 2026. To date, a total of 50 trials have been initiated, enrolling a combined total of 8,889 participants.

Amgen has been a primary driver of Sotorasib's development, sponsoring 15 trials. Other key sponsors include the National Cancer Institute (NCI) and Memorial Sloan Kettering Cancer Center, each sponsoring three trials.

Initially, Sotorasib's development explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and broadened to a wide range of solid tumors, particularly those with the KRAS G12C mutation. Key conditions now being investigated include Non-Small Cell Lung Cancer (NSCLC), metastatic colorectal cancer, pancreatic cancer, and various advanced solid tumors. The development has also explored specific stages of lung cancer, such as Stage III and Stage IV, and metastatic forms of the disease.

The clinical program for Sotorasib has progressed through various phases, reflecting its journey from early exploration to advanced investigation. The majority of trials are in Phase 2 (19 trials) and Phase 1 (16 trials), indicating a strong focus on assessing efficacy, safety, and optimal dosing. There are also 7 trials combining Phase 1/Phase 2, and 4 trials have advanced to Phase 3, evaluating Sotorasib against existing treatments in larger patient populations. This progression underscores the ongoing commitment to understanding Sotorasib's full potential as a targeted therapy.