Amgen’s Lumakras (ingredient: sotorasib), the world’s first KRAS mutation inhibitor developed over 40 years, arrived in the Korean market.

The treatment is indicated for non-small cell lung cancer (NSCLC). However, as it recently showed anticancer effects in pancreatic cancer, the marketing approval raises expectations for advancing the treatment of KRAS G12C mutated cancer patients who demonstrate poor prognosis, observers said.

The Ministry of Food and Drug Safety said Monday it approved once-daily Lumakras 960 mg for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received at least one prior systemic therapy.

Lumakras is the first KRAS targeted therapy developed over 40 years after researchers discovered KRAS as an oncogene. In addition, it is the first-in-class KRAS G12C inhibitor.

KRAS mutations vary according to the mutation type and location. Among them, KRAS G12C is a single-point mutation with a glycine-to cysteine substitution at codon 12, and it accounts for 44 percent of all KRAS mutations.

NSCLC patients with KRAS G12C mutation usually have resistance to existing therapy, showing lower survival rates in surgery or chemotherapy compared to other types of cancer patients.

Amgen’s Lumakras obtained the nod based on the phase-1/2 CodeBreak 100 trial results of NSCLC patients.

In 124 NSCLC patients with KRAS G12C mutation who have been previously treated with chemotherapy and immunotherapy, those treated with sotorasib showed a 36 percent objective response rate (ORR), and 58 percent of them demonstrated treatment response for six months or longer.

Lumakras won conditional approval from the MFDS, and Amgen can finalize the permit through a confirmatory clinical trial.

Lumakras signaled anticancer activities in pancreatic cancer patients, too.

results on Lumakras in pancreatic cancer drew particular attention when the American Society of Clinical Oncology designated them as the monthly plenary series topic this month.

According to data first released by ASCO on Monday, Lumakras showed a partial response rate (PR) of 21.1 percent in 38 patients with stage-four pancreatic cancer who participated in CodeBreaK 100 during the median follow-up 16.8 months. It also showed 3.98-month median progression-free survival (PFS) and 6.87-month median overall survival (OS).

Professor Lee Chung-keun of Yonsei Cancer Center said this study was phase 1/2. As a result, patients with various clinical characteristics were mixed, making it difficult to determine how much sotorasib could improve patient prognosis in real clinical settings before looking at detailed data and large-scale study results.

Still, given that most of the patients in the study used sotorasib in third or higher-line treatment, the study results were quite encouraging, he said.

Just like in lung cancer and colorectal cancer, patients with pancreatic cancer with KRAS G12C mutation tend to have a worse prognosis than those without such mutation, Lee said.

Second or third-line therapy treated pancreatic cancer patients’ OS and PFS were 6.2 months and 3.1 months, respectively. Although the response rate was 17 percent in the phase 3 NAPOLI-1 study, the latest CodeBreaK 100 data was noteworthy because most of the patients received third-line or higher therapy, he added.

On the news of the local approval for Lumakras, Lee raised anticipation for pancreatic cancer treatment. Although the number of pancreatic cancer patients with KRAS G12C mutation is very small, Kumakras could change the treatment environment of pancreatic cancer, the worse cancer in prognosis to date, he said.

Lee said it is unclear how much KRAS G12C mutation takes up in pancreatic cancer in Korea because there is no large-scale gene analysis data. However, Asian data shows the proportion is about 1 percent, and the Korean data is assumed to be similar, he said.

So far, Korean doctors have not done next-generation sequencing (NGS) on pancreatic cancer patients because it was almost impossible to use targeted therapy for them, Lee went on to say.

However, the regulatory nod for Lumakras could provide an opportunity to do gene analysis in more pancreatic cancer patients to discover a cancer target, he added.