Sotorasib + Panitumumab + FOLFIRI for Colorectal Cancer

(CodeBreaK 301 Trial)

Recruiting at 240 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Disqualifiers: Brain metastases, Leptomeningeal 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: 2

Duration: Up to 3 years

450 Participants Needed

Trial Summary

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 coordinators or your doctor.

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

Research suggests that combining sotorasib and panitumumab shows promise for treating colorectal cancer with the KRAS p.G12C mutation, which is hard to treat with standard therapies. Additionally, panitumumab has been effective in various studies for metastatic colorectal cancer, especially when combined with other chemotherapy drugs like FOLFIRI. ^{1 2 3 4 5}

What safety data exists for the combination of Sotorasib, Panitumumab, and FOLFIRI in colorectal cancer treatment?

Panitumumab has been evaluated for safety in patients with metastatic colorectal cancer, showing it can be used safely in certain conditions. Sotorasib has also been studied for safety in colorectal cancer with KRASG12C mutations, indicating it is generally safe for use in humans. ^{4 6 7 8 9}

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

This drug combination is unique because it targets the KRAS p.G12C mutation in metastatic colorectal cancer, which is a challenging condition to treat with standard therapies. Sotorasib specifically targets this mutation, while Panitumumab enhances the treatment by targeting the epidermal growth factor receptor, offering a personalized approach for patients with this specific genetic profile. ^{1 2 10 11 12}

What is the purpose of this trial?

The aim of this study is to compare progression free survival (PFS) in treatment-naïve Participants with KRAS p.G12C mutated metastatic colorectal cancer (mCRC) receiving sotorasib, panitumumab and FOLFIRI vs FOLFIRI with or without bevacizumab-awwb.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

This trial is for adults with a specific mutation (KRAS p.G12C) in metastatic colorectal cancer who haven't been treated before. They should have measurable disease, be relatively active and well (ECOG ≤ 1), and have organs that are functioning properly.

Inclusion Criteria

Measurable metastatic disease per RECIST v1.1 criteria

My colorectal cancer has a specific KRAS mutation.

My organs are working well.

Exclusion Criteria

I have brain metastases that haven't been treated.

My cancer has spread to the lining of my brain and spinal cord.

I have had or currently have lung scarring or inflammation.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Sotorasib, Panitumumab, and FOLFIRI or FOLFIRI with or without Bevacizumab-awwb

Up to 3 years

Every 2 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Treatment Details

Interventions

• Bevacizumab-awwb
• Panitumumab
• Sotorasib

Trial Overview The study is testing if adding Sotorasib and Panitumumab to the FOLFIRI regimen improves progression free survival compared to just FOLFIRI alone or with Bevacizumab-awwb in patients with this particular genetic form of colorectal cancer.

Participant Groups

Group I: Arm A: Sotorasib + Panitumumab + FOLFIRI Experimental Treatment 3 Interventions

Sotorasib was taken daily (QD) as an oral tablet. Panitumumab and FOLFIRI were received every 2 weeks (Q2W) via intravenous infusion (IV).

Group II: Arm B: FOLFIRI with or Without Bevacizumab-awwb Active Control 2 Interventions

Participants received FOLFIRI Q2W with or without bevacizumab-awwb.

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 phase II trial involving 96 patients with untreated RAS wild-type metastatic colorectal cancer, the addition of panitumumab to the chemotherapy regimen mFOLFOXIRI significantly improved the objective response rate (ORR) to 87.3% compared to 60.6% for the control group, indicating enhanced treatment efficacy.

The combination therapy also increased the rate of secondary surgical resection of metastases from 12.1% to 33.3%, suggesting a potential for better management of metastatic disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). Modest, DP., Martens, UM., Riera-Knorrenschild, J., et al.[2020]

In a study of 154 patients with metastatic colorectal carcinoma (mCRC), the combination of panitumumab and FOLFIRI showed a higher objective response rate (ORR) in patients with RAS wild type (WT) tumors (59%) compared to those with RAS mutant (MT) tumors (41%).

The treatment was well tolerated, with no new safety concerns, and patients with RAS WT tumors experienced longer median response durations (13.0 months) and progression-free survival (11.2 months) compared to those with RAS MT tumors (5.8 months and 7.3 months, respectively).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer. Karthaus, M., Hofheinz, RD., Mineur, L., et al.[2018]

In a study of 52 patients with cetuximab-refractory metastatic colorectal cancer, panitumumab did not show significant efficacy, as only 17 out of 41 patients were alive without progression at 2 months, failing to meet the predefined success criteria.

The median progression-free survival was only 2.1 months, and while most patients tolerated the treatment well, 25% experienced a grade 3 rash, indicating some safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial. Piccirillo, MC., Avallone, A., Carlomagno, C., et al.[2021]

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 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]

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 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 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 study of 77 patients with wild-type KRAS metastatic colorectal cancer, both treatment combinations of panitumumab with FOLFOX4 and FOLFIRI showed high objective response rates (ORR) of 74% and 67%, respectively, indicating their effectiveness in treating this condition.

Surgical resection rates were also promising, with 45% of patients on Pmab-FOLFOX4 and 59% on Pmab-FOLFIRI undergoing surgery, suggesting that both regimens can lead to potentially curative outcomes without significant differences in overall efficacy, although Pmab-FOLFOX4 was associated with higher rates of severe neutropenia and neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD). Carrato, A., Abad, A., Massuti, B., et al.[2018]

In a trial involving 1,053 patients with metastatic colorectal cancer, the addition of panitumumab to standard chemotherapy resulted in worse progression-free survival (PFS) compared to chemotherapy alone, with median PFS of 10.0 months versus 11.4 months.

Patients receiving panitumumab experienced significantly higher rates of severe side effects, including skin toxicity (36% vs. 1%) and diarrhea (24% vs. 13%), leading to the conclusion that this treatment combination is not recommended due to increased toxicity without improved efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. Hecht, JR., Mitchell, E., Chidiac, T., et al.[2022]

The combination of panitumumab and rilotumumab showed a promising objective response rate (ORR) of 31% in patients with wild-type KRAS metastatic colorectal cancer, indicating potential efficacy for this treatment strategy.

No dose-limiting toxicities were reported in the phase Ib study, suggesting that the combination therapy is safe and tolerable for patients, with manageable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. Van Cutsem, E., Eng, C., Nowara, E., et al.[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

FOLFOXIRI Plus Panitumumab As First-Line Treatment of RAS Wild-Type Metastatic Colorectal Cancer: The Randomized, Open-Label, Phase II VOLFI Study (AIO KRK0109). [2020]

3. England pubmed.ncbi.nlm.nih.gov

Impact of tumour RAS/BRAF status in a first-line study of panitumumab + FOLFIRI in patients with metastatic colorectal cancer. [2018]

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

Multicenter Single-Arm, Two-Stage Phase 2 Study of Panitumumab in Patients With Cetuximab-Refractory Metastatic Colorectal Cancer: The PACER Trial. [2021]

5. 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]

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

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

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. 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]

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

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

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

First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD). [2018]

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

A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. [2022]

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

Randomized phase Ib/II trial of rilotumumab or ganitumab with panitumumab versus panitumumab alone in patients with wild-type KRAS metastatic colorectal cancer. [2021]