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New Medicines

Lumykras (UK), Lumakras (US)Metastatic, KRAS G12c mutated non-small cell lung cancer (NSCLC) - second-line therapy or greater

Information

Lumykras (UK), Lumakras (US)
New molecular entity
Amgen
Amgen

Development and Regulatory status

Approved (Licensed)
Pre-registration (Filed)
Launched
Yes
Sep 21Approved UK licensed indication for Lumykras is monotherapy for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), who have progressed on, or are intolerant to, platinum-based chemotherapy and/or anti PD-1/PD-L1 immunotherapy [17].
Sep 21MHRA approves sotorasib (Lumakras) for advanced NSCLC patients whose tumors harbor a KRAS G12C mutation. The NHS will begin offering the drug to lung cancer patients in England after reaching an agreement with Amgen and NICE to provide it on a budget-neutral basis. NICE is still conducting an economic appraisal, which is necessary to convert the conditional approval into full approval. The drug was approved through Project Orbis, the second one after osimertinib. The NHS estimates that about 600 patients each year will be eligible for treatment with sotorasib [14,15].
Aug 21Lumakras is available in the US, with more than 2,000 patients having received the drug at more than 1,000 treatment sites [16].
Jun 21Sotorasib approved in the US to treat adults with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by the FDA-approved Guardant360 CDx test, in pts who have received at least 1 prior systemic therapy. Approval was based on results from a subset of pts in the PII CodeBreak 100 study. Sotorasib will continue to be assessed in clinical studies to affirm its efficacy and safety. [13]
Apr 21Amgen reports that some MAAs are under review under the Project Orbis initiative [13].
Apr 21Reported as filed in UK [12].
Feb 21Accepted by FDA for priority review with a decision expected by August 2021 [11].
Dec 20Amgen submits a marketing authorisation application to the EMA for sotorasib for previously-treated KRAS G12C-mutated NSCLC. The EMA submission is supported by results from the PII study, CodeBreaK 100 (NCT03600883) [9].
Dec 20Amgen has filed a submission with the FDA based on the results of the CodeBreaK 100 trial. This drug has been awarded breakthrough designation by the FDA [8].
Dec 20Amgen announce intention to file by the end of 2020, with launch anticipated for 2021 [7].
Sep 20Granted fast track designation for NSCLC in the US [5].
Jun 19Granted orphan drug status for NSCLC in the US [5].

Category

An orally bioavailable potent and selective KRAS G12C covalent small molecule inhibitor, first-in-class
KRAS G12C is one of the most prevalent driver mutations in NSCLC, ~13% of pts with non-squamous NSCLC in the US have this mutation. [13]
Metastatic, KRAS G12c mutated non-small cell lung cancer (NSCLC) - second-line therapy or greater
Oral

Further information

Yes

Trial or other data

Jun 20PIII randomised, open-label CodeBreak 200 trial (NCT04303780; EudraCT-2019‐003582‐18) initiated to compare AMG-510 (sotorasib) with docetaxel in previously-treated NSCLC patients (n=650 planned) with KRAS G12c mutation. Trial sites are worldwide, incl the US, Europe and UK. Primary outcome measure is PFS. Estimated primary completion date is November 2021 [5,6].
Dec 19PI/II trial (NCT03600883) is recruiting & now due to completion collection of primary outcome data in Apr 23 [4].
Sep 19Data presented at ESMO for 12 pts with colorectal cancer who were treated with max 960mg dose showed only one pt saw a PR, and 10 had stable disease for a disease control rate of 92%. There were no major adverse safety worries attached to the test [3].
Aug 18First-in-human PI/II trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AMG-510 as monotherapy and in combination with an anti PD-1/L1, in patients with KRAS p.G12C mutant locally-advanced or metastatic solid tumours, including non-small cell lung cancer and colorectal cancer starts (NCT03600883). The open-label, non-randomised trial intends to enrol approximately 158 adults in the US, Australia, Canada, France, Japan and South Korea. Collection of primary outcome data is expected to complete Dec 22 [2].

Evidence based evaluations