Sotorasib + Panitumumab for Colorectal Cancer

(CodeBreak300 Trial)

Recruiting at 121 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

160 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two doses of sotorasib combined with panitumumab in patients with a specific type of colorectal cancer that has not responded to other treatments. Sotorasib targets a genetic mutation in the cancer cells, while panitumumab helps the immune system attack the cancer. The goal is to see if this combination can help patients live longer without their cancer getting worse.

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.

What data supports the effectiveness of the drug combination Sotorasib and Panitumumab for colorectal cancer?

Research shows that the combination of sotorasib and panitumumab has potential in treating colorectal cancer with the KRAS p.G12C mutation, offering a personalized approach. Sotorasib alone has shown modest benefits, with a disease control rate of 82.3%, while panitumumab has improved response rates and progression-free survival in patients with KRAS wild-type metastatic colorectal cancer. ^{1 2 3 4 5}

Is the combination of Sotorasib and Panitumumab safe for treating colorectal cancer?

Panitumumab has been associated with side effects like skin rash, low magnesium levels, and serious conditions like lung issues and severe skin reactions. Sotorasib has been studied for safety in colorectal cancer, but specific safety data for the combination of Sotorasib and Panitumumab is not detailed in the available research. ^{6 7 8 9 10}

What makes the drug combination of Sotorasib and Panitumumab unique for colorectal cancer?

The combination of Sotorasib and Panitumumab is unique because it targets specific mutations in colorectal cancer, particularly the KRAS p.G12C mutation, which is not effectively addressed by standard therapies. Sotorasib inhibits the KRAS mutation, while Panitumumab targets the epidermal growth factor receptor (EGFR), offering a personalized treatment approach for patients with this mutation. ^{1 4 11 12 13}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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, 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]

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]

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, 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Revolutionizing KRAS p.G12C therapy in metastatic colorectal cancer: The triumph of dual inhibition. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Panitumumab after progression on cetuximab in KRAS wild-type metastatic colorectal cancer patients: a single institution experience. [2018]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Targeting colorectal cancer with anti-epidermal growth factor receptor antibodies: focus on panitumumab. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Panitumumab: a summary of clinical development in colorectal cancer and future directions. [2018]

6. Italy 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. [2021]

7. England 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. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018]

9. England pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: panitumumab (Vectibix). [2018]

10. England pubmed.ncbi.nlm.nih.gov

FDA review of a panitumumab (Vectibix) clinical trial for first-line treatment of metastatic colorectal cancer. [2018]

11. United States 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. [2020]

12. New Zealand pubmed.ncbi.nlm.nih.gov

Spotlight on panitumumab in metastatic colorectal cancer. [2018]

13. New Zealand pubmed.ncbi.nlm.nih.gov

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