Roche Presents Promising Phase Ib Results at the 2023 AACR Conference, Strengthening Divarasib's Potential as a KRAS G12C Inhibitor for Advanced Solid

The phase Ib GO42144 study found that when divarasib was paired with cetuximab, an anti-EGFR therapy, it resulted in a confirmed overall response rate of 62% among individuals with advanced colorectal cancer. The treatment combination was also proven to be safe and manageable. These findings, which were presented at AACR 2023, further emphasize Roche's commitment to developing divarasib either as a standalone treatment or in combination therapy to target solid tumours.

Roche, a pharmaceutical company, has shared positive results from their study called GO42144. This study focused on using a new medication called divarasib (also known as GDC-6036) to treat people with advanced or metastatic KRAS G12C-positive colorectal cancer (CRC). The study found that when divarasib was used in combination with another medication called cetuximab, it led to an overall response rate of 62%. Additionally, the combination of divarasib and cetuximab was shown to be safe. These findings were presented at the American Association for Cancer Research Annual Meeting on April 17, 2023 at 2:50pm ET.

Colorectal cancer (CRC) is a prevalent form of cancer worldwide, ranking third for its frequency. Unfortunately, the number of cases is expected to increase by 56% between the years 2020 and 2040, with over three million new cases per year. Additionally, CRC is responsible for a significant number of cancer-related deaths. Those who have CRC and KRAS mutations tend to experience more aggressive tumour growth, leading to a poorer prognosis.

The information presented confirms that divarasib in combination with EGFR inhibition may have the best potential for treating individuals with KRAS G12C mutated CRC. Levi Garraway, who is the Chief Medical Officer and Head of Global Product Development at Roche, stated this in his commentary. KRAS mutations are known to have a negative impact on the prognosis of different types of tumors, including colorectal cancer. The data obtained from this study is likely to contribute towards the advancement of new treatment options for patients with KRAS G12C mutations, which is much needed.

Data from the GO42144 study's phase Ib have shown that combining divarasib with cetuximab, which is an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, results in positive clinical activity and manageable safety in patients with advanced or metastatic KRAS G12C-positive CRC. 66% of patients (19 out of 29) achieved an overall response that is yet to be confirmed, while 62% (18 out of 29) had a confirmed overall response. All patients had experienced at least one treatment-related adverse event (TRAE), which led to grade ≥3 TRAEs among 41% of patients (12 out of 29). None of the patients had to stop taking the medication due to adverse effects.1

Studies have shown that by blocking the EGFR, the tumour may become more sensitive to KRAS G12C inhibition in CRC. This could potentially overcome resistance to KRAS G12C inhibition alone. These findings support previous research on divarasib treatment and highlight its effective anti-tumour activity in tumours with KRAS G12C mutations. At the 2022 Annual Meeting of the European Society of Medical Oncology (ESMO), data was presented showing that divarasib on its own achieved an overall response in 41% (16/39) of patients with KRAS G12C-positive CRC treated with a 400mg dose, with 31% (12/39) of these cases confirmed.

Roche has a development program in progress for divarasib that aims to enhance treatment outcomes in treating solid tumors with the KRAS G12C mutation. The drug is presently under investigation in Phase I trials in both combination with other anti-cancer treatments and as a single-agent to treat non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and other solid tumors. Divarasib is also a subject of a global Phase II/III research project (B-FAST; NCT03178552) being conducted on individuals suffering from advanced NSCLC.

The GO42144 study [NCT04449874] is currently underway and focusing on dose escalation and expansion in phase I/Ib. It aims to assess how safe and effective divarasib (GDC-6036) is when given alone or in combination with other cancer treatments. The study is geared towards patients who have advanced or metastatic solid tumours with a KRAS G12C mutation. Different kinds of tumours such as non-small cell lung cancer, colorectal cancer (CRC), and advanced solid tumours are being analyzed.

During phase Ib of the research, 29 participants had advanced or metastatic CRC that was KRAS G12C-positive. These participants already had two prior treatments for their metastatic therapy. They were given divarasib as well as cetuximab until they developed intolerable toxicity or disease progression. The participants took the study treatment for an average of 5.5 months. The study's objectives included safety evaluation (by NCI-CTCAE v5), examining the pharmacokinetics, and assessing the preliminary anti-tumour activity (using RECIST V1.1).

The article is talking about a drug called Divarasib (GDC-6036) which is currently being studied for its effectiveness in treating several types of cancer. This drug is an oral medication that specifically targets a protein called KRAS G12C, which is known to play a role in the growth of tumors. By locking this protein into an inactive state, Divarasib is able to prevent the growth of cancer cells. Researchers are currently studying Divarasib's potential as a KRAS G12C inhibitor and trying to determine if it can be an effective treatment for other types of cancer as well.

The KRAS G12C mutation is connected to colorectal cancer. This type of cancer is quite common around the world and is responsible for a lot of cancer-related deaths. The number of new cases per year is projected to increase over time. Unfortunately, there aren't very many treatment options available for those who have advanced colorectal cancer. In Europe and the US, a lot of people won't receive any further treatment after two rounds of therapy. This is because there aren't many third-line treatment options, and the overall survival rate decreases significantly from second to third-line treatment.

About 40% of colorectal cancer cases have KRAS mutations, while approximately 4% of cases have the KRAS G12C mutation. These mutations are associated with worse outcomes and more aggressive cancer growth, which underscores the importance of developing fresh treatments for advanced colorectal cancer.

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The blog section contains a list of references related to a study on GDC-6036, a potential treatment for colorectal cancer patients with a mutation called KRAS G12C. The study was presented at the American Association for Cancer Research Annual Meeting in 2023, and it showed promising results for the treatment's effectiveness. Other references provide information on colorectal cancer awareness and the role of KRAS in diagnosing and treating the disease. The list also includes clinical trial information and data on the probability of receiving second and further lines of therapy for metastatic colorectal cancer patients.

On April 18, 2023, Roche Holding AG released this written material and takes full responsibility for the details presented in it. It has been distributed to the public without any editing or alterations, as of April 18, 2023, at 05:12:07 UTC.