Table of Contents
- Overview of the clinical trial program
- Who can join these studies
- Trial phases and what they mean
- Main cancer types being studied
- What the trials measure
- Special study designs and combinations
- Trial-by-trial summary
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.[1] Most studies focus on cancers with a KRAS G12C or KRAS p.G12C mutation, which means the tumor has a specific gene change.[1]
The studies are interventional, which means patients receive a treatment and the research team measures the effects.[1] The program includes early studies that look at safety and dose, and later studies that compare how well treatments work against other options.[1]
Who can join these studies
Many trials are for adults with advanced, metastatic, locally advanced, or unresectable cancer.[1] Unresectable means the cancer cannot be removed with surgery.[1]
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.[1] One study includes people with comorbidities, which means other health problems are also present.[1]
There is also a study in healthy subjects, but that trial is for drug interaction testing rather than cancer treatment.[1]
Trial phases and what they mean
The studies include Phase 1, Phase 2, Phase 3, and combined Phase 1/2 designs.[1] Phase 1 studies mainly check safety, tolerability, and dose finding.[1]
Phase 2 studies look more closely at how well Sotorasib helps control cancer, often by measuring tumor response or progression-free survival.[1] Phase 3 studies are larger and compare Sotorasib-based treatment with other standard treatments or treatment choices.[1]
Main cancer types being studied
Non-small cell lung cancer (NSCLC) is the most common cancer type in these trials.[1] Studies include previously treated NSCLC, first-line NSCLC, advanced NSCLC, metastatic NSCLC, and unresectable stage III NSCLC.[1]
Colorectal cancer is another major focus, including metastatic colorectal cancer, advanced unresectable colorectal adenocarcinoma, and resectable primary colorectal cancer in a pre-surgery study.[1] There is also a study in advanced pancreatic adenocarcinoma.[1]
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.[1]
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.[1] Several studies define progression using RECIST v1.1, a standard set of rules for measuring tumor changes on scans.[1]
Another common endpoint is objective response rate (ORR), which means the percentage of patients whose tumors shrink enough to count as a response.[1] Some studies also look at overall survival (OS), which is the time from treatment start until death.[1]
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.[1] A few studies also measure pathology results after surgery, biomarkers, or resistance to treatment.[1]
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.[1] These combination studies try to see whether adding Sotorasib can improve tumor control or help in specific patient groups.[1]
One colorectal cancer study is a single-arm trial, which means everyone gets the same treatment and there is no comparison group.[1] Another study is a rollover study, which follows people who were already benefiting from earlier Amgen-sponsored studies and lets them continue treatment.[1]
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.[1] In some cohorts, the study also checks whether surgery happens on time.[1]
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.[1]
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.[2]
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.[3]
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.[4]
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.[5]
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.[6]
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.[7]
NCT05311709 is a Phase 2 study in advanced KRAS G12C-mutated NSCLC patients with comorbidities, with ORR as the main endpoint.[8]
NCT05398094 is a Phase 2 study in unresectable stage III KRAS p.G12C NSCLC, measuring PFS at 6 months after induction treatment.[9]
2024-516233-12-00 is a Phase 1 study in advanced pancreatic adenocarcinoma focused on safety and tolerability of Sotorasib with first-line chemotherapy.[10]
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.[11]
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.[12]
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.[13]
2023-505557-41-00 is a completed Phase 3 healthy-subject study that examined how rivaroxaban behaves with and without Sotorasib.[14]
NCT05074810 is a Phase 1 study of avutometinib plus Sotorasib in G12C NSCLC patients, with dose-limiting toxicities and confirmed response as key outcomes.[15]
