Table of Contents
- Trial overview
- Non-small cell lung cancer studies
- Colorectal cancer studies
- Early-phase safety and dose-finding studies
- What the trials measure
- Who may join these trials
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.[1][2] Most studies focus on cancers with a KRAS G12C mutation, especially non-small cell lung cancer and colorectal cancer.[1][5]
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.[1][8] The enrollment sizes range from 68 to 821 participants, so some studies are small and focused while others are much larger.[6][8]
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.[1][2][5][6] Some studies test Adagrasib alone, while others combine it with pembrolizumab, chemotherapy, or other study drugs to see whether the combination improves outcomes.[2][7][8]
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.[1] Its main measure is Objective Response Rate (ORR), which means how many tumors shrink enough to count as a response on scans.[1]
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.[2] 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.[2]
Another Phase 2 study tests Adagrasib in first-line advanced NSCLC, both alone and with pembrolizumab and chemotherapy.[7] 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.[7]
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.[5] This study checks ORR at 12 weeks to see how many patients respond early to treatment.[5]
A Phase 3 study compares Adagrasib with docetaxel in previously treated advanced NSCLC with the KRAS G12C mutation.[6] Its main endpoint is PFS, so the study asks whether Adagrasib can delay disease progression better than the comparison treatment.[6]
Colorectal cancer studies
Adagrasib is also being studied in advanced colorectal cancer with the KRAS G12C mutation.[4] 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.[4]
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.[4] 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.[3]
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.[4] In the colorectal cancer parts, the study compares response rates and safety across different combinations.[4]
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.[3][4] 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.[3][4]
One Phase 1 study tested INCB099280 with Adagrasib in adults with advanced solid tumors carrying the KRAS G12C mutation.[3] Its goals were to study safety and tolerability and to find the maximum tolerated dose (MTD) or a recommended dose for later testing.[3]
Another Phase 1 study tested BMS-986466 with Adagrasib, with or without cetuximab, in KRAS G12C-mutant solid tumors.[4] 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.[4]
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.[1][5][7] 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.[1][2][5]
Later-phase studies also measure PFS and OS, which are key outcomes in cancer research.[2][4][6] Early-phase studies focus more on safety outcomes such as dose-limiting toxicities, serious adverse events, treatment interruptions, dose reductions, and treatment stopping.[3][4]
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.[1][3][4] Some studies include people who have already received treatment, while others are for previously untreated disease.[1][2][6]
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.[5] Other studies include broader groups such as advanced solid tumors, NSCLC, or colorectal cancer, depending on the treatment combination being tested.[3][4][7]
