Sotorasib + Panitumumab for Colorectal Cancer

(CodeBreak300 Trial)

Not currently recruiting at 145 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Must not be taking: KRAS G12C inhibitors

Disqualifiers: Active brain metastases, Hematological malignancies, Significant GI disorder, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best treatment for individuals with a specific type of colorectal cancer that has a KRAS mutation. It compares two experimental treatment combinations: sotorasib (a new potential drug) and panitumumab (Vectibix, a monoclonal antibody therapy), against standard treatments typically chosen by doctors. Participants should have metastatic colorectal cancer with the KRAS p.G12C mutation and must have tried at least one other treatment. The goal is to determine which option helps patients live longer without their cancer worsening. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants access to potentially groundbreaking treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of sotorasib and panitumumab is generally well-tolerated by patients with a specific type of colorectal cancer. Studies have found this treatment to be safe for most people. Some patients experienced side effects, but these were usually manageable.

In one study, many patients reported an improvement in their quality of life while taking sotorasib with panitumumab, indicating that the benefits often outweighed the side effects. Although there is a risk of side effects, the treatment has demonstrated a balance that many patients find acceptable. Anyone considering joining a trial should discuss the possible risks and benefits with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of sotorasib and panitumumab for colorectal cancer because it offers a novel approach to targeting cancer cells. Unlike most treatments for colorectal cancer that focus on chemotherapy drugs like FOLFOX or FOLFIRI, sotorasib specifically targets a mutation in the KRAS gene, which is present in a significant number of colorectal cancer cases. This precision in targeting the KRAS mutation could potentially lead to more effective and less toxic outcomes. Additionally, the use of panitumumab, an EGFR inhibitor, alongside sotorasib could enhance the overall anticancer effect by blocking cancer cell growth signals from multiple angles. This dual-action approach is what has researchers hopeful about its potential to improve treatment outcomes for patients with this challenging form of cancer.

What evidence suggests that this trial's treatments could be effective for colorectal cancer?

Research has shown that using sotorasib and panitumumab together may help treat colorectal cancer with the KRAS mutation. In this trial, participants in Arm A will receive Sotorasib 960 mg QD with panitumumab, while those in Arm B will receive Sotorasib 240 mg QD with panitumumab. A study found that patients taking these drugs lived for an average of 5.6 months without their cancer worsening, which is longer than with other treatments. Additionally, tumors shrank in about 26.4% of cases. This suggests that this drug combination might work better than traditional treatments for this specific type of cancer. ^{1 5 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults over 18 with metastatic colorectal cancer that has a specific mutation (KRAS p.G12C) can join this trial. They must have tried at least one other treatment and their cancer should be measurable by certain medical criteria. Good organ function and performance status are required, but those with severe skin, breast, or prostate conditions without current disease, brain metastases treated over 4 weeks ago without progression, or other cancers cured more than 3 years ago may also qualify.

Inclusion Criteria

- International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) ≤1.5 x ULN. Prothrombin time (PT) ≤1.5 x ULN may be used instead of INR for sites whose labs do not report INR.

- Fridericia's Correction Formula (QTcF) ≤470 msec.

My cancer can be measured by scans and has grown after any radiation treatments.

Exclusion Criteria

My bladder cancer has been treated and is not invasive.

I had skin cancer (not melanoma) treated and currently show no signs of it.

My cancer was treated over 3 years ago, with no current signs of it and considered low risk for coming back.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sotorasib and panitumumab or investigator's choice of trifluridine and tipiracil, or regorafenib

8 weeks

Baseline and Week 8 assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Approximately 2 years

Long-term monitoring

Participants are monitored for treatment-emergent adverse events and other long-term outcomes

Approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Panitumumab
• Regorafenib
• Sotorasib
• Trifluridine and Tipiracil

Trial Overview The study is testing the effectiveness of Sotorasib combined with Panitumumab against either Trifluridine/Tipiracil or Regorafenib in patients whose colorectal cancer has progressed after previous treatments. The main goal is to see which combination helps slow down the cancer's growth better.

How Is the Trial Designed?

Group I: Arm B: Sotorasib 240 mg QD + panitumumab Experimental Treatment 2 Interventions

Group II: Arm A: Sotorasib 960 mg QD + panitumumab Experimental Treatment 2 Interventions

Group III: Arm C : Investigator's choice Active Control 2 Interventions

Participants will be administered trifluridine and tipiracil, or regorafenib

Panitumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Approved in United States as Vectibix for:

• Metastatic colorectal cancer (mCRC) with wild-type KRAS

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a phase II clinical trial, the KRAS inhibitor sotorasib showed a 9.7% objective response rate in patients with advanced or metastatic KRASG12C-mutant colorectal cancer, indicating some level of effectiveness.

The disease control rate was notably high at 82.3%, and patients experienced a progression-free survival of 4 months, suggesting that sotorasib can help manage the disease in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib's Benefits in Colorectal Cancer Modest. [2022]

In a phase II trial involving 53 patients with advanced wild-type K-RAS colorectal cancer, the combination of panitumumab and irinotecan every 3 weeks demonstrated safety and efficacy, with 23% of patients achieving partial responses and 41% achieving disease stabilization.

The treatment resulted in a median progression-free survival of 4.5 months and an overall survival of 15.1 months, with skin toxicity being significantly associated with clinical response, indicating that monitoring for skin reactions could be important in treatment evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer. Carrato, A., Gómez, A., Escudero, P., et al.[2021]

In a phase 2 study involving 148 patients with metastatic colorectal cancer, panitumumab demonstrated a 9% overall response rate and a median progression-free survival of 14 weeks, indicating its efficacy as a treatment option for patients who had previously failed other therapies.

Panitumumab was generally well tolerated, with manageable side effects; 95% of patients experienced skin toxicity, but only 5% had severe reactions, suggesting that while dermatologic issues are common, they are not typically severe.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. Hecht, JR., Patnaik, A., Berlin, J., et al.[2018]

Panitumumab (Vectibix) was evaluated in a trial with 463 patients suffering from advanced colorectal cancer, showing a mean progression-free survival (PFS) of 96 days compared to 60 days for those receiving only best supportive care, indicating a significant benefit in delaying disease progression.

Despite the improvement in PFS and an objective response rate of 8%, there was no difference in overall survival between the treatment groups, leading to accelerated approval by the FDA with the requirement for further confirmation of clinical benefit for full approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

U.S. Food and Drug Administration approval: panitumumab for epidermal growth factor receptor-expressing metastatic colorectal carcinoma with progression following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Giusti, RM., Shastri, K., Pilaro, AM., et al.[2020]

Panitumumab, when combined with chemotherapy, significantly prolongs progression-free survival in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival compared to chemotherapy alone, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab: a review of its use in metastatic colorectal cancer. Keating, GM.[2021]

In a phase 2 trial involving 62 patients with KRASG12C-mutant colorectal cancer, sotorasib demonstrated a modest objective response rate of 9.7%, indicating some anti-tumor activity in patients who had previously undergone extensive treatment.

The safety profile of sotorasib was manageable, with 10% of patients experiencing grade 3 adverse events, primarily diarrhea, and no fatal events reported, suggesting it could be a viable option for heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial. Fakih, MG., Kopetz, S., Kuboki, Y., et al.[2022]

The study emphasizes the potential of combining sotorasib and panitumumab as a treatment for patients with refractory metastatic colorectal cancer who have the KRAS p.G12C mutation, addressing a significant unmet medical need.

This combination therapy may offer a promising personalized treatment option, as standard therapies have shown limited success in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revolutionizing KRAS p.G12C therapy in metastatic colorectal cancer: The triumph of dual inhibition. Ottaiano, A., Santorsola, M.[2023]

In a retrospective analysis of 25 patients with KRAS wild-type metastatic colorectal cancer who progressed after cetuximab treatment, panitumumab showed promising activity, with a median progression-free survival of 5 months and overall survival of 8 months.

Despite the previous treatment failure, 25% of patients experienced stable disease for at least 9 months, and the treatment was generally well-tolerated, with minimal severe side effects, indicating that panitumumab may be a viable option for patients seeking continued treatment without chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Panitumumab after progression on cetuximab in KRAS wild-type metastatic colorectal cancer patients: a single institution experience. Marino, A., Caliolo, C., Sponziello, F., et al.[2018]

Panitumumab, approved for treating metastatic colorectal cancer, significantly improved progression-free survival (PFS) compared to best supportive care alone, with median PFS times of 56 days versus 51 days, respectively, in a study of 463 patients.

While panitumumab showed efficacy in delaying disease progression, it did not improve overall survival, and common side effects included skin rash and hypomagnesemia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). Giusti, RM., Shastri, KA., Cohen, MH., et al.[2018]

Panitumumab, an anti-EGFR monoclonal antibody, significantly improves progression-free survival when combined with chemotherapy in patients with wild-type KRAS metastatic colorectal cancer, but shows no overall survival benefit in second-line treatment.

In patients with mutant KRAS tumors, panitumumab is less effective, leading to shorter progression-free survival when combined with certain chemotherapy regimens, highlighting the importance of KRAS mutation status in treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. Keating, GM.[2018]

A clinical trial showed that adding panitumumab to bevacizumab and chemotherapy for first-line treatment of metastatic colorectal cancer resulted in worse progression-free survival and increased toxicity compared to bevacizumab and chemotherapy alone.

Patients receiving panitumumab experienced a higher incidence of severe adverse events (87% vs. 72%) and a greater risk of death (9% vs. 4%), leading to the conclusion that panitumumab should not be recommended in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. Giusti, RM., Cohen, MH., Keegan, P., et al.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308795

Sotorasib plus Panitumumab in Refractory Colorectal ... Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0 ...

2. amgen.com amgen.com/newsroom/press-releases/2025/01/fda-approves-lumakras-sotorasib-in-combination-with-vectibix-panitumumab-for-chemorefractory-kras-g12cmutated-metastatic-colorectal-cancer

FDA APPROVES LUMAKRAS® (SOTORASIB) IN ... Study results demonstrated that LUMAKRAS 960 mg daily plus Vectibix (n=53) showed an improved median PFS of 5.6 months (4.2, 6.3) compared to 2 ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO-24-02026

Overall Survival Analysis of the Phase III CodeBreaK 300 ... In the phase III CodeBreaK 300 study, sotorasib 960 mg-panitumumab significantly prolonged progression-free survival (PFS) versus investigator's choice.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/pubmed/37870968/

Sotorasib plus Panitumumab in Refractory Colorectal ... Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0 ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer

FDA approves sotorasib with panitumumab for KRAS ... The study was not statistically powered for OS. Median PFS was 5.6 months (95% CI: 4.2, 6.3) in the sotorasib 960 mg/panitumumab arm and 2 ...

6. amgen.com amgen.com/newsroom/press-releases/2021/09/lumakras-sotorasib-combined-with-vectibix-panitumumab-showed-encouraging-efficacy-and-safety-in-patients-with-kras-g12cmutated-colorectal-cancer

LUMAKRAS™ (Sotorasib) Combined With Vectibix® ... LUMAKRAS (Sotorasib) combined with Vectibix (Panitumumab) showed encouraging efficacy and safety in patients with KRAS G12C-mutated colorectal cancer.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37870968/

Sotorasib plus Panitumumab in Refractory Colorectal ... Overall survival data are maturing. The objective response was 26.4% (95% CI, 15.3 to 40.3), 5.7% (95% CI, 1.2 to 15.7), and 0 ...

8. thelancet.com thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00352-3/fulltext

Health-related quality of life in patients with KRAS G12C ... The results of this study showed an overall improvement in several PRO measures from baseline to week 9 with sotorasib plus panitumumab compared ...