What Is Adagrasib?
Adagrasib is an investigational medication being studied for various types of cancer. It is a type of drug known as a KRAS G12C inhibitor. This means it is designed to specifically target and block the activity of a mutated KRAS protein, which can contribute to cancer growth. By inhibiting this specific mutation, Adagrasib aims to slow or stop the progression of cancers that carry the KRAS G12C genetic alteration. It is given by mouth, with a specified dose on specified days.
While specific FDA approvals are not detailed in the provided context, Adagrasib is being investigated in clinical trials for conditions such as metastatic cancer, advanced cancer, and non-small cell lung cancer (NSCLC). Approximately 30% of patients with NSCLC present with resectable disease, but many experience relapse after surgery. Despite advances in therapy for advanced NSCLC, new systemic neoadjuvant therapies are still being sought.
Uses and Conditions Under Study
Adagrasib is currently being studied in clinical trials for several types of cancer. Across 26 trials with a total enrollment of 4,147 participants, the drug is being investigated for its potential to treat various malignant conditions.
- General Cancers: Adagrasib is being evaluated for broad categories of cancer, including Metastatic Cancer (4 trials), Advanced Cancer (4 trials), Advanced Solid Tumors (2 trials), and Malignant Neoplastic Disease (2 trials). As a KRAS G12C inhibitor, it targets a specific genetic mutation found in various tumor types, making it potentially useful across different advanced cancers.
- Lung Cancer: Specifically, Adagrasib is under investigation for Non Small Cell Lung Cancer (NSCLC) in 2 trials, NSCLC (2 trials), and Malignant Neoplasm of Lung (2 trials). NSCLC is a common type of lung cancer, and targeting the KRAS G12C mutation may offer a new therapeutic option for patients whose tumors carry this specific genetic change.
- Colorectal Cancer: The drug is also being studied for Metastatic Colorectal Cancer (2 trials) and Colorectal Cancer (CRC) (1 trial). Colorectal cancer can also harbor KRAS mutations, and Adagrasib aims to address these specific genetic drivers of the disease.
- Dynamic Tumor Resistance: One trial is exploring Adagrasib in the context of Dynamic Tumor Resistance, indicating research into how the drug might overcome mechanisms by which tumors become resistant to treatment.
Dosing
Adagrasib is administered orally, meaning it is taken by mouth. Clinical trials have investigated various dosing regimens and combinations. The drug has been studied both as a monotherapy and in combination with other treatments.
Specific dosages of Adagrasib studied include Adagrasib 600mg BID (twice daily) and Adagrasib 400mg BID. It is often given on specified days as part of a treatment cycle. In some trials, Adagrasib is part of a combination treatment, such as:
- Combo Treatment with Izalontamab Brengitecan (IV) + Adagrasib (PO) Q3W (every 3 weeks)
- Adagrasib + SRS (Stereotactic Radiosurgery)
- Adagrasib + Olaparib
- Combination with BMS-986488, with or without Cetuximab or Nivolumab
- Combination with tremelimumab and durvalumab
- Combination with bevacizumab
- Combination with avutometinib (VS-6766)
- Combination with SAR442720, with or without Pembrolizumab
These various dosage forms and combinations are being explored in different phases of trials, including dose-finding, dose escalation, and dose expansion cohorts, to determine the most effective and safest treatment approaches for different cancer types.
Side Effects
Specific frequencies for individual side effects of Adagrasib are not detailed in the provided study data. However, overall adverse event occurrences were reported in clinical trials where Adagrasib was administered in combination with other agents.
In Part 3A of the study NCT04418661, when Adagrasib was combined with SAR442720 (100mg BIW):
- No participants experienced treatment-emergent adverse events (TEAEs).
- One participant experienced a treatment-emergent serious adverse event (TESAE).
- No participants experienced treatment-related dose-limiting toxicities (DLTs).
In Part 1 of the study NCT06024174, when Adagrasib (400mg BID) was combined with BMS-986466 (10mg):
- Four participants experienced adverse events (AEs).
- One participant experienced a serious adverse event (SAE).
- No participants experienced AEs leading to discontinuation.
- No participants experienced dose-limiting toxicities (DLTs).
- No participants died.
Clinical Trial Results
Clinical efficacy results for Adagrasib were evaluated in combination with other agents in specific study parts.
Results from NCT04418661
In Part 3A of this study, which investigated Adagrasib in combination with SAR442720 (100mg BIW), the objective response rate (ORR) was observed to be 0% of participants. Plasma concentrations of Adagrasib in this combination ranged from 0 ng/mL to 2910 ng/mL.
Results from NCT06024174
Part 1 of this study explored Adagrasib (400mg BID) in combination with BMS-986466 (10mg). Efficacy outcomes, such as objective response rate, progression-free survival, or duration of response, were not reported for this specific part of the trial. Pharmacokinetic measures, including the area under the serum concentration-time curve (AUC[0-T]), maximum observed plasma concentration (Cmax), and time to maximum concentration (Tmax), were reported as not available (NA).
Currently Recruiting Trials
Adagrasib is currently being investigated in several clinical trials for various cancers, offering opportunities for patients to participate in the advancement of new treatment options. These studies explore Adagrasib both as a standalone therapy and in combination with other medications. One phase II trial, NCT07288034, sponsored by City of Hope Medical Center, is enrolling up to 535 participants with stage IIIB-IV non-small cell lung cancer (NSCLC). This study aims to understand how biomarkers can predict the response to initial immunotherapy and guide the selection of second-line treatments, including combinations involving Adagrasib and bevacizumab in one of its arms. For patients with previously untreated, locally advanced or metastatic non-squamous NSCLC with a KRAS G12C mutation, the KRYSTAL-4 trial, NCT06875310, is a phase III study sponsored by Mirati Therapeutics Inc. It seeks to enroll 630 participants to evaluate Adagrasib combined with pembrolizumab and chemotherapy against a placebo-based regimen. Another study, NCT06412198, is a phase Ib/II trial from M.D. Anderson Cancer Center focusing on metastatic colorectal cancer harboring KRAS G12C mutations. This trial plans to enroll 31 participants to assess the combination of Adagrasib, cetuximab, and cemiplimab. Patients with KRAS G12C-mutated NSCLC who have untreated brain metastases may be eligible for NCT06248606. This phase II trial, led by Ryan Gentzler, MD, will enroll 30 participants to evaluate Adagrasib combined with stereotactic radiosurgery (SRS). Kura Oncology, Inc. is sponsoring NCT06026410, a phase I study exploring KO-2806, a farnesyltransferase inhibitor, as monotherapy and in combination with other agents in advanced solid tumors, including NSCLC, colorectal cancer, and pancreatic ductal adenocarcinoma. Adagrasib is part of the combination therapies being explored in this trial, which targets 300 participants. Mirati Therapeutics Inc. also sponsors NCT05609578, a phase II trial investigating Adagrasib in combination with pembrolizumab and chemotherapy for advanced NSCLC with KRAS G12C mutation, aiming for 90 participants. Finally, the KRYSTAL-7 trial, NCT04613596, is a phase II/III study from Mirati Therapeutics Inc. with an enrollment target of 806 participants. It evaluates Adagrasib monotherapy and in combination with pembrolizumab for advanced or metastatic NSCLC with a KRAS G12C mutation, particularly for first-line treatment candidates.Where to Participate
Adagrasib clinical trials have a broad geographic reach, with studies underway at 383 sites across 245 cities in 42 states. This widespread availability helps ensure that many patients can access these investigational treatments. Top locations for participation include:- Jacksonville, Florida (10 sites)
- Nashville, Tennessee (8 sites)
- Boston, Massachusetts (6 sites)
- Dallas, Texas (6 sites)
- Denver, Colorado (6 sites)
- Chicago, Illinois (5 sites)
- Los Angeles, California (5 sites)
- Safford, Arizona (5 sites)
- Minneapolis, Minnesota (4 sites)
- Somerset, New Jersey (4 sites)