Sotorasib, Panitumumab and FOLFIRI compared to FOLFIRI with or without Bevacizumab-awwb in previously untreated patients with metastatic colorectal cancer with KRAS p.G12C mutation (CodeBreaK 301)

Zusammenfassung der Studie

This study is being conducted to learn more about the combination therapies of Sotorasib, Panitumumab, and FOLFIRI (Irinotecan, Leucovorin, and 5-Fluorouracil [5-FU]) in people with metastatic colorectal cancer with KRAS p.G12C mutation who have not previously received systemic therapy for their metastatic disease. The aim of this study is to compare these combinations of study drugs in terms of efficacy (how well they work), survival, safety, and tolerability (how one feels during the intake of the study drugs). Participants will be randomly assigned to one of 2 treatment groups. They will either receive Sotorasib, Panitumumab, and FOLFIRI (Group 1 / Arm A) or FOLFIRI with or without Bevacizumab-awwb (Group 2 / Arm B). The study lasts a total of about 5 years and is divided into the following phases: - Screening Phase (up to 28 days): up to 3 appointments - Treatment Phase (10 – 16 months): 2 appointments per cycle (cycle duration of 28 days) - Safety Follow-up: 1 appointment within 30 days (+7 days) after the last dose - Long-term Follow-up (up to 5 years): Every 12 weeks (± 4 weeks)

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Untersuchte Intervention

Sotorasib is a cancer drug developed for tumors with a specific mutation called KRAS p.G12C. Panitumumab is an antibody (a protein component of the immune system) that prevents growth signals from reaching cancer cells. Bevacizumab-awwb (MVASI) is a biosimilar of the active substance Bevacizumab (Avastin). Biosimilar means that a product is similar to another biological medicine (biologic) that is already approved for the treatment of cancer. Bevacizumab-awwb binds to the vascular endothelial growth factor (VEGF) (a type of protein) and can prevent the growth of new blood vessels that tumors need for their continued growth.

Performance study: This study is a combined study that also includes an additional part: the assessment of a test to determine the presence of the KRAS p.G12C mutation in your tumor sample. The KRAS p.G12C test is still under investigation and has not been approved by any health authority (e.g., the U.S. Food and Drug Administration [FDA]) for use in patients with mCRC tumors with KRAS p.G12C mutation for treatment with Sotorasib. This additional assessment is called a performance study. It will be conducted in parallel with the main study. It aims to show whether the test is useful and safe to identify people with a KRAS p.G12C mutation. The performance study, that is, the assessment of this test, is sponsored by a company called Qiagen. Qiagen is the manufacturer of the test. No additional samples will be taken from you for the performance study unless an additional biopsy is needed to determine if you qualify for the study. The performance study is part of this research study. If you consent to participate in the Sotorasib research study, you also agree to participate in the performance study. For the performance study, Amgen obtains the consent on behalf of Qiagen. Qiagen receives the results of the diagnostic test and the test data collected for the performance study. You should discuss the schedule for laboratory results with your doctor.

Sotorasib is developed by Amgen Inc., a for-profit biopharmaceutical company. Sotorasib has been approved by various health authorities for use in adult patients with non-small cell lung cancer (NSCLC) that has spread to other parts of the body or cannot be surgically removed, whose tumor has an abnormal KRAS p.G12C gene and who have received at least one prior cancer treatment. Among other things, it has received conditional or accelerated approval (i.e., studies to confirm clinical benefit are still ongoing) from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Sotorasib, an active ingredient that can be taken orally daily, is still under investigation in combination with other medications and for other tumors than NSCLC, such as mCRC.

Panitumumab is also manufactured by Amgen Inc. Panitumumab is administered by infusion and is approved by the U.S. FDA for mCRC without Rous sarcoma virus (RAS) mutation(s) for administration alone or in combination with chemotherapy for colorectal cancer that has spread to other parts of the body. Panitumumab is not approved for the treatment of mCRC (the tumor being studied in this clinical trial) with a KRAS mutation, as studies have shown that it does not work for mCRC with a KRAS mutation. However, it is possible that Panitumumab may work on the tumor when combined with a drug that inhibits the mutated KRAS protein. Sotorasib in combination with Panitumumab is still under investigation and has not yet been approved by any health authority (such as the U.S. FDA or EMA). Sotorasib and Panitumumab are not approved in combination with FOLFIRI, even though FOLFIRI is approved for the treatment of metastatic colorectal cancer, including mCRC with possible KRAS p.G12C mutation.

As part of this study, you may receive Bevacizumab-awwb as an intravenous injection. Bevacizumab-awwb (MVASI) was developed by Amgen Inc. and has been approved by the EMA and U.S. FDA for the treatment of various cancers, including mCRC, in combination with chemotherapy.

FOLFIRI is administered by infusion and is approved by health authorities (e.g., the U.S. FDA) for use as combination chemotherapy for mCRC regardless of KRAS mutation status.

Participants are randomly assigned to groups. In this study, there are 2 groups:

• Group 1 (Treatment Arm A) receives Sotorasib (1 time daily), Panitumumab (2 times per cycle (28 days)) and FOLFIRI (2 times per cycle (28 days))

• Group 2 (Treatment Arm B) receives FOLFIRI (2 times per cycle (28 days)) with or without Bevacizumab-awwb (2 times per cycle (28 days)). The doctor decides whether the participant will receive Bevacizumab-awwb or not.

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Untersuchte Krankheit(en)

Colorectal cancer (CRC)

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Sponsor

Sponsor: Amgen Inc, Thousand Oaks, CA, USA Sponsor’s representative in Switzerland: Amgen Switzerland AG, Rotkreuz

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Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)

Ethikkommission Zürich

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Datum der Bewilligung durch die Ethikkommission

06.09.2024

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Ergebnisse der Studie