Sotorasib + Panitumumab + FOLFIRI for Colorectal Cancer

(CodeBreaK 301 Trial)

Recruiting at 371 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of treatments for individuals with a specific type of colorectal cancer that has metastasized. It aims to determine if using sotorasib (a new potential drug) and panitumumab with a chemotherapy regimen called FOLFIRI is more effective than FOLFIRI alone or with another drug, bevacizumab-awwb. The trial focuses on participants who have not received prior treatment and have a KRAS p.G12C mutation in their cancer. Suitable candidates have colorectal cancer that has spread and tested positive for the KRAS p.G12C genetic mutation. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research shows that the combination of sotorasib, panitumumab, and FOLFIRI is likely safe for patients with a certain type of colorectal cancer. Previous studies found that people with KRAS G12C-mutated metastatic colorectal cancer, who had already received treatment, tolerated this combination well. Serious side effects occurred infrequently, indicating long-term safety.

These results suggest the treatment might also be safe for new patients. However, discussing any concerns or possible side effects with a doctor is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sotorasib combined with Panitumumab and FOLFIRI for colorectal cancer because it introduces a novel approach to treatment. Sotorasib targets the KRAS G12C mutation, a common genetic alteration in colorectal cancer that is often hard to treat with existing therapies. Unlike the standard of care, which typically involves chemotherapy alone or with other drugs like bevacizumab, this combination leverages Sotorasib's ability to specifically inhibit the mutated KRAS protein, potentially offering a more effective and targeted treatment option. Additionally, Panitumumab, an antibody targeting the EGFR pathway, enhances this targeted approach, possibly improving outcomes for patients who do not respond well to traditional treatments.

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

Research has shown that a combination of the drugs sotorasib, panitumumab, and FOLFIRI, which participants in Arm A of this trial will receive, may be promising for treating metastatic colorectal cancer (mCRC) with the KRAS G12C mutation. One study found that this combination had a strong overall response rate of 57% in patients who had already tried other treatments, meaning that more than half of the patients experienced a significant reduction in tumor size. The treatment also had manageable side effects, considered tolerable. These findings suggest that this combination could be an effective option for people with this specific type of mCRC. ^{1 3 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 been treated with a KRAS p.G12C inhibitor before.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

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

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

Participants will receive 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

Published Research Related to This Trial

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]

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 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 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]

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 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 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 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 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]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3506

CodeBreaK 101 (phase 1b). | Journal of Clinical Oncology Conclusions: Sotorasib plus panitumumab and FOLFIRI showed promising long-term safety and efficacy in pretreated KRAS G12C-mutated mCRC. AEs ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS326

A phase 3 study of first-line sotorasib, panitumumab, and ... The current study aims to evaluate whether the combination of sotorasib, panitumumab, and FOLFIRI is superior to FOLFIRI with or without bevacizumab-awwb, a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06252649

NCT06252649 | Study of Sotorasib, Panitumumab and ... The aim of this study is to compare progression free survival (PFS) in treatment-naïve participants with KRAS p.G12C mutated metastatic colorectal cancer ...

4. onclive.com onclive.com/view/dr-strickler-on-the-efficacy-of-sotorasib-plus-panitumumab-chemo-in-kras-g12c-mcrc

Dr Strickler on the Efficacy of Sotorasib Plus Panitumumab ... What we found is that the ORR was quite robust for a heavily pretreated group of patients [with mCRC] at 57%, [with] a [median] progression-free ...

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02093-3/fulltext

505O Sotorasib (soto), panitumumab (pani) and FOLFIRI in ... This study provides the first data set on the use of a KRASG12C inhibitor in 1L mCRC. The combination of soto, pani, and FOLFIRI demonstrated a tolerable safety ...

6. annalsofoncology.org annalsofoncology.org/article/S0923-7534(23)04433-2/fulltext

92MO Sotorasib (Soto) + panitumumab (Pmab) and ... These data confirm the promising safety and efficacy for Soto + Pmab and FOLFIRI in previously treated KRAS G12C-mutated mCRC. Data on progression-free survival ...

7. asco.org asco.org/videos-slides/VIDEOSANDSLIDES244748

Long-term safety and efficacy of sotorasib plus ... Long-term safety and efficacy of sotorasib plus panitumumab and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreaK ...

8. amgentrials.com amgentrials.com/study/?id=20210081

AMGEN - Study of Sotorasib, Panitumumab and FOLFIRI ... The aim of this study is to compare progression free survival (PFS) in treatment-naïve participants with KRAS p.G12C mutated metastatic colorectal cancer ...