Sotorasib + Panitumumab + FOLFIRI for Colorectal Cancer

(CodeBreaK 301 Trial)

Recruiting in Palo Alto (17 mi)

+174 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Amgen

Disqualifiers: Brain metastases, Leptomeningeal disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

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.

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}

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.

Trial 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 (Angiogenesis Inhibitor)
• Panitumumab (Monoclonal Antibodies)
• Sotorasib (Targeted Therapy)

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Cancer Specialists of North Florida Jacksonville, FL

Providence Saint Jude Medical Center Fullerton, CA

Cancer and Blood Specialty Clinic Los Alamitos, CA

D and H Cancer Research Center Margate, FL

More Trial Locations

Who Is Running the Clinical Trial?

Amgen Lead Sponsor

References

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

Revolutionizing KRAS p.G12C therapy in metastatic colorectal cancer: The triumph of dual inhibition. [2023] The management of refractory metastatic colorectal cancer patients with the KRAS p.G12C mutation presents a significant unmet need, with limited success using standard therapies. The study by Fakih et al. highlights the potential of sotorasib and panitumumab combination therapy in this clinical context, paving the way for a promising personalized therapeutic approach.1.

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] Label="PURPOSE">This trial investigated the addition of panitumumab to triplet chemotherapy with fluorouracil/folinic acid, oxaliplatin, and irinotecan (FOLFOXIRI) in a two-to-one randomized, controlled, open-label, phase II trial in patients with untreated RAS wild-type (WT) metastatic colorectal cancer.

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] To investigate tumour biomarker status and efficacy of first-line panitumumab+FOLFIRI for metastatic colorectal carcinoma (mCRC).

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] To assess whether panitumumab is active in patients with cetuximab-refractory metastatic colorectal cancer (mCRC).

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] Few data describe the activity of panitumumab after cetuximab-irinotecan-based regimen failure in patients with KRAS wild-type metastatic colorectal cancer (WT MCRC).

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

Panitumumab monotherapy in patients with previously treated metastatic colorectal cancer. [2018] The safety and efficacy of the fully human antibody panitumumab was evaluated in patients with metastatic colorectal cancer refractory to available therapies.

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] Label="BACKGROUND">Sotorasib, a specific, irreversible KRASG12C protein inhibitor, has shown monotherapy clinical activity in KRASG12C-mutated solid tumours, including colorectal cancer, in the CodeBreaK100 phase 1 trial. We aimed to investigate the activity and safety of sotorasib in phase 2 of the trial.

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] To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC).

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

Sotorasib's Benefits in Colorectal Cancer Modest. [2022] The KRAS inhibitor sotorasib provides some clinical benefit in patients with advanced or metastatic KRASG12C-mutant colorectal cancer, according to results of a phase II clinical trial. The objective response rate was 9.7%, the disease control rate was 82.3%, and the progression-free survival was 4 months.

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] In first-line wild-type (WT)-Kirsten rat sarcoma viral oncogene homologue (KRAS) metastatic colorectal cancer (mCRC), panitumumab (Pmab) improves outcomes when added to FOLFOX [folinic acid, 5-fluorouracil, and oxaliplatin] or FOLFIRI [folinic acid, 5-fluorouracil, and irinotecan]. However no trial has directly compared these combinations.

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] Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.

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] Panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody (mAb), has demonstrated efficacy in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Rilotumumab and ganitumab are investigational, fully human mAbs against hepatocyte growth factor (HGF)/scatter factor and IGF1R, respectively. Here we evaluate combining rilotumumab or ganitumab with panitumumab in previously treated patients with wild-type KRAS mCRC.