In short
Clinical trials are studying Adagrasib in people with KRAS G12C-mutant cancers, mainly non-small cell lung cancer and colorectal cancer. These studies look at how well it works, how safe it is, and whether it helps when used alone or with other cancer treatments. The trials include people with advanced, untreated, or previously treated disease.
Key points
- Clinical trials of Adagrasib are mostly studying cancers with the KRAS G12C mutation, especially non-small cell lung cancer and colorectal cancer. The trial set includes early studies that focus on safety and dose, as well as larger studies that measure tumor response, progression-free survival, and overall survival. Some trials test Adagrasib alone, while others combine it with pembrolizumab, chemotherapy, cetuximab, or other study drugs. The target groups include people with newly diagnosed advanced disease, previously treated disease, older adults, and patients with poor performance status. Several trials are already authorised, and some completed studies have looked at safety, tolerability, and the best dose for future testing.
Trial overview
The trial data shows that Adagrasib is being studied in interventional cancer trials, which means researchers give a treatment and then measure the results. Most studies focus on cancers with a KRAS G12C mutation, especially non-small cell lung cancer and colorectal cancer.
The studies include Phase 1, Phase 2, Phase 3, and one study listed as Phase 4, showing that Adagrasib is being tested from early safety work to larger comparison trials. The enrollment sizes range from 68 to 821 participants, so some studies are small and focused while others are much larger.
Non-small cell lung cancer studies
Several trials study Adagrasib in non-small cell lung cancer (NSCLC), including people with locally advanced, metastatic, or previously treated disease. Some studies test Adagrasib alone, while others combine it with pembrolizumab, chemotherapy, or other study drugs to see whether the combination improves outcomes.
One Phase 2 study compares two dosing regimens of Adagrasib in people with NSCLC who already had platinum-based treatment and immune checkpoint inhibitor therapy. Its main measure is Objective Response Rate (ORR), which means how many tumors shrink enough to count as a response on scans.
A Phase 3 study called KRYSTAL-4 compares Adagrasib plus pembrolizumab plus chemotherapy with placebo plus pembrolizumab plus chemotherapy in people with previously untreated, locally advanced or metastatic non-squamous NSCLC. This study looks at progression-free survival and overall survival, which show how long the cancer stays controlled and how long people live after treatment starts.
Another Phase 2 study tests Adagrasib in first-line advanced NSCLC, both alone and with pembrolizumab and chemotherapy. That study measures ORR in some cohorts and PFS at 6 months in another cohort, which means whether the cancer stays controlled for at least six months.
There is also a Phase 2 study designed for people with KRAS G12C-mutant NSCLC who are elderly or who have poor performance status, meaning they are less physically fit because of their cancer. This study checks ORR at 12 weeks to see how many patients respond early to treatment.
A Phase 3 study compares Adagrasib with docetaxel in previously treated advanced NSCLC with the KRAS G12C mutation. Its main endpoint is PFS, so the study asks whether Adagrasib can delay disease progression better than the comparison treatment.
Colorectal cancer studies
Adagrasib is also being studied in advanced colorectal cancer with the KRAS G12C mutation. One large Phase 3 study compares Adagrasib plus cetuximab with standard chemotherapy in the second-line setting, meaning after one prior treatment has already been given.
That study measures both overall survival and progression-free survival, so it looks at how long people live and how long the cancer stays from getting worse. Another Phase 1 study includes advanced solid tumors with KRAS G12C mutation, and its plan includes colorectal cancer among the cancer types studied in the early dose-finding part.
One Phase 1/partly comparative study also includes colorectal cancer and tests Adagrasib with BMS-986466, with or without cetuximab, in KRAS G12C-mutant disease. In the colorectal cancer parts, the study compares response rates and safety across different combinations.
Early-phase safety and dose-finding studies
Early-phase studies are important because they help researchers learn whether a treatment is safe enough for larger trials and what dose should be used next. In these studies, researchers watch for dose-limiting toxicities, which are side effects that are severe enough to stop dose increases, and they also record adverse events, meaning unwanted medical problems during treatment.
One Phase 1 study tested INCB099280 with Adagrasib in adults with advanced solid tumors carrying the KRAS G12C mutation. Its goals were to study safety and tolerability and to find the maximum tolerated dose (MTD) or a recommended dose for later testing.
Another Phase 1 study tested BMS-986466 with Adagrasib, with or without cetuximab, in KRAS G12C-mutant solid tumors. This study also looked for the maximum tolerated dose or maximum administered dose, and it measured whether the treatment was safe and whether tumors responded.
What the trials measure
The most common cancer response measure in these studies is ORR, which is based on RECIST 1.1, a standard way to measure tumor size on scans. Some trials use ORR at a fixed time point, such as 12 weeks, while others use investigator review or blinded independent central review, which means scan results are checked by study doctors or outside reviewers.
Later-phase studies also measure PFS and OS, which are key outcomes in cancer research. Early-phase studies focus more on safety outcomes such as dose-limiting toxicities, serious adverse events, treatment interruptions, dose reductions, and treatment stopping.
Who may join these trials
Eligibility depends on the trial, but all studies in this set require a cancer with the KRAS G12C mutation or a related group of KRAS G12C-mutant solid tumors. Some studies include people who have already received treatment, while others are for previously untreated disease.
One study is designed for older adults or patients with poor performance status, which means people who are less able to handle intensive treatment because of their overall health. Other studies include broader groups such as advanced solid tumors, NSCLC, or colorectal cancer, depending on the treatment combination being tested.