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]