In short
Clinical trials are studying Sotorasib in people with certain cancers, especially KRAS G12C or KRAS p.G12C mutation-positive tumors. These studies look at safety, tumor response, progression-free survival, and overall survival in different patient groups, including lung, colorectal, pancreatic, and other solid tumors.
Key points
- Sotorasib is being studied in several clinical trials for cancers with a KRAS G12C or KRAS p.G12C mutation. The main focus is non-small cell lung cancer and colorectal cancer, but there are also studies in pancreatic cancer, other solid tumors, and healthy subjects for a drug interaction test. Trial phases range from Phase 1 to Phase 3, so the research includes early safety checks and larger comparisons of how well treatment works. Common endpoints include progression-free survival, overall survival, objective response rate, and treatment safety. Some trials also study surgery timing, biomarkers, and resistance to treatment. The studies include people with advanced, metastatic, unresectable, or previously treated disease, and some trials test Sotorasib in combination with other cancer treatments.
Overview of the clinical trial program
The trial program for Sotorasib includes studies in several cancer types and in healthy subjects for one interaction study. Most studies focus on cancers with a KRAS G12C or KRAS p.G12C mutation, which means the tumor has a specific gene change.
The studies are interventional, which means patients receive a treatment and the research team measures the effects. The program includes early studies that look at safety and dose, and later studies that compare how well treatments work against other options.
Who can join these studies
Many trials are for adults with advanced, metastatic, locally advanced, or unresectable cancer. Unresectable means the cancer cannot be removed with surgery.
Some studies include people who already had treatment before, while others are for first-line treatment, which means the first treatment given for the cancer. One study includes people with comorbidities, which means other health problems are also present.
There is also a study in healthy subjects, but that trial is for drug interaction testing rather than cancer treatment.
Trial phases and what they mean
The studies include Phase 1, Phase 2, Phase 3, and combined Phase 1/2 designs. Phase 1 studies mainly check safety, tolerability, and dose finding.
Phase 2 studies look more closely at how well Sotorasib helps control cancer, often by measuring tumor response or progression-free survival. Phase 3 studies are larger and compare Sotorasib-based treatment with other standard treatments or treatment choices.
Main cancer types being studied
Non-small cell lung cancer (NSCLC) is the most common cancer type in these trials. Studies include previously treated NSCLC, first-line NSCLC, advanced NSCLC, metastatic NSCLC, and unresectable stage III NSCLC.
Colorectal cancer is another major focus, including metastatic colorectal cancer, advanced unresectable colorectal adenocarcinoma, and resectable primary colorectal cancer in a pre-surgery study. There is also a study in advanced pancreatic adenocarcinoma.
One large Phase 1/2 study includes advanced solid tumors with the KRAS p.G12C mutation, which means several cancer types were eligible if they had that mutation.
What the trials measure
A common endpoint is progression-free survival (PFS), which is the time before the cancer gets worse or the patient dies. Several studies define progression using RECIST v1.1, a standard set of rules for measuring tumor changes on scans.
Another common endpoint is objective response rate (ORR), which means the percentage of patients whose tumors shrink enough to count as a response. Some studies also look at overall survival (OS), which is the time from treatment start until death.
Safety is also important. Some trials measure treatment-emergent adverse events, serious adverse events, dose-limiting toxicities, lab changes, and changes in vital signs or physical exams. A few studies also measure pathology results after surgery, biomarkers, or resistance to treatment.
Special study designs and combinations
Some trials test Sotorasib alone, while others test it with other cancer treatments such as panitumumab, chemotherapy, pembrolizumab, or avutometinib. These combination studies try to see whether adding Sotorasib can improve tumor control or help in specific patient groups.
One colorectal cancer study is a single-arm trial, which means everyone gets the same treatment and there is no comparison group. Another study is a rollover study, which follows people who were already benefiting from earlier Amgen-sponsored studies and lets them continue treatment.
The UNICORN pre-operative study looks at short-course treatment before surgery and measures major pathological response, which means how much the tumor changes in tissue samples after treatment. In some cohorts, the study also checks whether surgery happens on time.
Trial-by-trial summary
NCT03600883 is a large Phase 1/2 study in KRAS p.G12C mutant advanced solid tumors, with safety and response endpoints across several parts of the trial.
NCT04303780 is a Phase 3 study in previously treated locally advanced or metastatic NSCLC, comparing Sotorasib with docetaxel and using PFS as the main endpoint.
NCT05920356 is a Phase 3 trial in PD-L1 negative, KRAS p.G12C positive advanced or metastatic NSCLC, comparing Sotorasib plus chemotherapy with pembrolizumab plus chemotherapy and measuring PFS and OS.
NCT05198934 is a completed Phase 3 colorectal cancer study comparing Sotorasib plus panitumumab with investigator’s choice treatment and using PFS by blinded central review.
2022-502352-31-00 is a Phase 3 first-line metastatic colorectal cancer study comparing Sotorasib, panitumumab, and FOLFIRI against FOLFIRI with or without bevacizumab, with PFS as the main endpoint.
NCT04933695 is a completed Phase 2 first-line NSCLC study that measured objective response in patients whose tumors had PD-L1 TPS below 1 percent and/or an STK11 co-mutation.
2024-510837-16-00 is a Phase 2 NSCLC study that looks at response at 4 months and also studies biomarkers linked to early and later resistance.
NCT05311709 is a Phase 2 study in advanced KRAS G12C-mutated NSCLC patients with comorbidities, with ORR as the main endpoint.
NCT05398094 is a Phase 2 study in unresectable stage III KRAS p.G12C NSCLC, measuring PFS at 6 months after induction treatment.
2024-516233-12-00 is a Phase 1 study in advanced pancreatic adenocarcinoma focused on safety and tolerability of Sotorasib with first-line chemotherapy.
2024-514030-20-00 is a Phase 2 colorectal cancer study in patients not eligible for doublet or triplet chemotherapy, with the rate of being alive without progression at 8 months as the main endpoint.
2022-501308-90-00 is a Phase 2 pre-operative colorectal cancer umbrella study that includes a Sotorasib cohort and measures major pathological response and, in some cohorts, timely surgery.
2025-522355-26-00 is a Phase 2 rollover study for people who keep benefiting from earlier studies, checking safety and tolerability of continued treatment with or without panitumumab and other anti-cancer therapies.
2023-505557-41-00 is a completed Phase 3 healthy-subject study that examined how rivaroxaban behaves with and without Sotorasib.
NCT05074810 is a Phase 1 study of avutometinib plus Sotorasib in G12C NSCLC patients, with dose-limiting toxicities and confirmed response as key outcomes.