Sotorasib provides durable clinical benefit for patients with NSCLC and KRAS mutations

January 28, 2021

(For Immediate Release--Singapore--January 28, 2021)-- In the phase II CodeBreak 100 trial, sotorasib provided durable clinical benefit with a favorable safety profile in patients with pretreated non-small cell lung cancer (NSCLC) and who harbor KRAS p.G12C mutations, validating CodeBreak 100's phase I results, according to research presented today at the International Association for the Study of Lung Cancer World Conference on Lung Cancer.

Outcome in patients with advanced NSCLC on second- or third-line therapies is poor, with a response rate of less than 20% and median progression-free survival of fewer than four months. Approximately 13% of patients with lung adenocarcinomas harbor KRAS p.G12C mutations.

Sotorasib is a first-in-class small molecule that specifically and irreversibly inhibits KRAS p.G12C. In the phase I cohort of the CodeBreak 100 trial, sotorasib was well tolerated and demonstrated a confirmed response rate of 32.2%, a median duration of response of 10.9 months, and a median progression-free survival of 6.3 months in 59 patients with heavily pretreated NSCLC.

Results from the registrational phase II portion of this multicenter, international study, led by Dr. Bob Li, of Memorial Sloan Kettering Cancer Center in New York City, were presented for the first time.

Researchers enrolled 126 patients who met the following inclusion criteria:Patients with untreated active brain metastases were excluded.

Enrolled patients were followed for a median period of 12.2 months. An independent blinded central review of the patients found that 124 patients had at least one measurable lesion at baseline and were evaluated for efficacy. Of these, 46 patients experienced a confirmed response (three complete responses and 43 partial responses), resulting in an objective response rate of 37.1% (95% Cl: 28.6-46.2). The median time to objective response was 1.4 months, the median duration of response was 10 months (95% CI: 6.9-11.1), and 43% of responders remained on treatment without progression. The disease control rate was 80.6% (95% Cl: 72.6-87.2).

Median progression-free survival was 6.8 months (95% Cl: 5.1-8.2).

Treatment-related adverse events (TRAEs) of any grade occurred in 88 (69.8%) patients and led to discontinuation in nine (7.1%) patients. Grade 3 TRAEs were reported in 25 (19.8%) patients; those that occurred most commonly were alanine aminotransferase increase (8/126, 6.3%), aspartate aminotransferase increase (7/126, 5.6%), and diarrhea (5/126, 4.0%). There were no treatment-related deaths.

"This is a historic milestone in [lung] cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need," said Dr. Li.

Further clinical trials of sotorasib, either alone or in combination with other cancer drugs, are ongoing in an effort to benefit more patients.

In December 2020, Amgen submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) and Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for sotorasib, for the treatment of patients with KRAS p.G12C-mutated locally advanced or metastatic NSCLC, following at least one prior systemic therapy. The NDA is being reviewed under the FDA's Real-Time Oncology Review pilot program and has been granted Breakthrough Therapy designation.

About the IASLC:

The International Association for the Study of Lung Cancer (IASLC) is the only global organization dedicated solely to the study of lung cancer and other thoracic malignancies. Founded in 1974, the association's membership includes nearly 7,500 lung cancer specialists across all disciplines in over 100 countries, forming a global network working together to conquer lung and thoracic cancers worldwide. The association also publishes the Journal of Thoracic Oncology, the primary educational and informational publication for topics relevant to the prevention, detection, diagnosis, and treatment of all thoracic malignancies. Visit for more information.

About the WCLC:

The WCLC is the world's largest meeting dedicated to lung cancer and other thoracic malignancies, attracting more than 7,000 researchers, physicians and specialists from more than 100 countries. The goal is to increase awareness, collaboration and understanding of lung cancer, and to help participants implement the latest developments across the globe. The conference will cover a wide range of disciplines and unveil several research studies and clinical trial results. For more information, visit

International Association for the Study of Lung Cancer

Related Lung Cancer Articles from Brightsurf:

State-level lung cancer screening rates not aligned with lung cancer burden in the US
A new study reports that state-level lung cancer screening rates were not aligned with lung cancer burden.

The lung microbiome may affect lung cancer pathogenesis and prognosis
Enrichment of the lungs with oral commensal microbes was associated with advanced stage disease, worse prognosis, and tumor progression in patients with lung cancer, according to results from a study published in Cancer Discovery, a journal of the American Association for Cancer Research.

New analysis finds lung cancer screening reduces rates of lung cancer-specific death
Low-dose CT screening methods may prevent one death per 250 at-risk adults screened, according to a meta-analysis of eight randomized controlled clinical trials of lung cancer screening.

'Social smokers' face disproportionate risk of death from lung disease and lung cancer
'Social smokers' are more than twice as likely to die of lung disease and more than eight times as likely to die of lung cancer than non-smokers, according to research presented at the European Respiratory Society International Congress.

Lung cancer therapy may improve outcomes of metastatic brain cancer
A medication commonly used to treat non-small cell lung cancer that has spread, or metastasized, may have benefits for patients with metastatic brain cancers, suggests a new review and analysis led by researchers at St.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Lung transplant patients face elevated lung cancer risk
In an American Journal of Transplantation study, lung cancer risk was increased after lung transplantation, especially in the native (non-transplanted) lung of single lung transplant recipients.

Proposed cancer treatment may boost lung cancer stem cells, study warns
Epigenetic therapies -- targeting enzymes that alter what genes are turned on or off in a cell -- are of growing interest in the cancer field as a way of making a cancer less aggressive or less malignant.

Are you at risk for lung cancer?
This question isn't only for people who've smoked a lot.

Read More: Lung Cancer News and Lung Cancer Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to