Amgen to debate software for LUMAKRAS® (sotorasib) for the therapy of KRAS G12C-positive NSCLC at FDA advisory committee assembly


Amgen as we speak introduced the U.S. Meals and Drug Administration (FDA) Oncologic Medicine Advisory Committee (ODAC) will assessment knowledge supporting the supplemental New Drug Utility (sNDA) for the complete approval of LUMAKRAS® (sotorasib) for adults with beforehand handled domestically superior or metastatic KRAS G12C-mutated non-small cell lung most cancers (NSCLC) at a gathering on Oct. 5, 2023.

LUMAKRAS/LUMYKRAS is accepted in a number of markets outdoors america together with Europe, South America, Asia and the European Union. Up to now, over 6,500 sufferers all over the world have obtained LUMAKRAS/LUMYKRAS by way of the scientific improvement program and business use.

Lumakras has demonstrated a good profit/threat profile in a number of research in non-small lung most cancers and different tumor sorts similar to colo-rectal most cancers. Amgen is progressing the most important and broadest international KRASG12C inhibitor improvement program exploring a number of mixture regimens, with scientific trial websites spanning 5 continents.

We consider within the scientific worth of LUMAKRAS for prescribers and sufferers navigating KRAS G12C-mutated NSCLC and we look ahead to discussing the great knowledge package deal for LUMAKRAS with members of the Committee.”

David M. Reese, M.D., Government Vice President of Analysis and Improvement, Amgen

LUMAKRAS obtained accelerated approval from the FDA on Could 28, 2021. The sNDA for full approval of LUMAKRAS was accepted by the FDA for normal assessment and a Prescription Drug Consumer Payment Act (PDUFA) goal motion date of Dec. 24, 2023, has been set.

About LUMAKRAS®/LUMYKRAS® (sotorasib) 

Amgen took on one of many hardest challenges of the final 40 years in most cancers analysis by creating LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS has demonstrated a optimistic benefit-risk profile with fast, deep, and sturdy anticancer exercise in sufferers with domestically superior or metastatic non-small cell lung most cancers (NSCLC) harboring the KRAS G12C mutation with a as soon as each day oral formulation.2

In Could 2021, LUMAKRAS was the primary KRASG12C inhibitor to obtain regulatory approval with its approval within the U.S., underneath accelerated approval. LUMAKRAS/LUMYKRAS can also be accepted within the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Turkey, Thailand, Qatar, Australia, Argentina, Brazil, Canada, Nice Britain, Kuwait, Macao, Singapore, Mexico, Israel, Bulgaria, Hungary, Romania, and Russia. Moreover, Amgen has submitted MAAs in Colombia, Malaysia and Saudi Arabia.

LUMAKRAS/LUMYKRAS can also be being studied in a number of different stable tumors. 

About non-small cell lung most cancers and the KRAS G12C mutation 

Lung most cancers is the main reason behind cancer-related deaths worldwide, and it accounts for extra deaths worldwide than colon most cancers, breast most cancers and prostate most cancers mixed.3 Total survival charges for NSCLC are enhancing however stay poor for sufferers with superior illness, and 5-year survival is just 9% for these with metastatic illness.4

KRAS G12C is the commonest KRAS mutation in NSCLC.About 13% of sufferers with NSCLC harbor the KRAS G12C mutation.6 The unmet medical want stays excessive and therapy choices are restricted for NSCLC sufferers with the KRAS G12C mutation whose first-line therapy has did not work or has stopped working. The outcomes with different accepted therapies are suboptimal, with a median progression-free survival of roughly 4 months following second-line therapy of KRAS G12C-mutated NSCLC.7

About CodeBreaK 

The CodeBreaK scientific improvement program for Amgen’s drug sotorasib is designed to review sufferers with a sophisticated stable tumor with the KRAS G12C mutation and deal with the longstanding unmet medical want for these cancers.   

CodeBreaK 100, the Part 1 and a pair of, first-in-human, open-label multicenter research, enrolled sufferers with KRAS G12C-mutant stable tumors.Eligible sufferers should have obtained a previous line of systemic anticancer remedy, per their tumor kind and stage of illness. The first endpoint for the Part 2 research was centrally assessed goal response fee. The Part 2 trial in NSCLC enrolled 126 sufferers, 124 of whom had centrally evaluable lesions by RECIST at baseline.2 The Part 2 trial in metastatic colorectal most cancers (mCRC) enrolled 62 sufferers and outcomes have been printed.9

CodeBreaK 200, the worldwide Part 3 multicenter, randomized, open-label, active-controlled research in contrast the efficacy, security, and tolerability of sotorasib to docetaxel in KRAS G12C-mutated NSCLC accomplished enrollment of 345 sufferers. Eligible sufferers had beforehand handled, domestically superior and unresectable or metastatic KRAS G12C-mutated NSCLC. The first endpoint was progression-free survival and key secondary endpoints included general survival, goal response fee, and patient-reported outcomes.10

CodeBreaK 300, the worldwide Part 3 randomized active-controlled research evaluating sotorasib together with panitumumab to investigator’s selection (trifluridine and tipiracil, or regorafenib) in chemorefractory KRAS G12C-mutated mCRC, has accomplished enrollment of 160 sufferers. Eligible sufferers had KRAS G12C-mutated mCRC, obtained at the least one prior line of remedy, and have obtained and progressed on or after fluoropyrimidine, irinotecan, and oxaliplatin. The first endpoint is progression-free survival and key secondary endpoints embody general survival (OS) and goal response fee (ORR).11

Amgen additionally has a number of Part 1b research investigating sotorasib together with a number of different therapies throughout numerous superior stable tumors (CodeBreaK 101) open for enrollment.12  A Part 3 randomized managed research will consider frontline sotorasib together with platinum doublet chemotherapy versus pembrolizumab platinum doublet mixture in sufferers with PD-L1-negative, superior KRAS G12C-mutated NSCLC (CodeBreaK 202).13

LUMAKRAS® (sotorasib) U.S. indication 

LUMAKRAS is indicated for the therapy of grownup sufferers with KRAS G12C-mutated domestically superior or metastatic non-small cell lung most cancers (NSCLC), as decided by an FDA-approved take a look at, who’ve obtained at the least one prior systemic remedy. 

This indication is accepted underneath accelerated approval based mostly on general response fee (ORR) and period of response (DOR). Continued approval for this indication could also be contingent upon verification and outline of scientific profit in a confirmatory trial(s). 

LUMAKRAS® (sotorasib) necessary U.S. security info 


  • LUMAKRAS may cause hepatotoxicity, which can result in drug-induced liver damage and hepatitis.
  • Amongst 357 sufferers who obtained LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A complete of 18% of sufferers who obtained LUMAKRAS had elevated alanine aminotransferase (ALT)/elevated aspartate aminotransferase (AST); 6% have been Grade 3 and 0.6% have been Grade 4. Along with dose interruption or discount, 5% of sufferers obtained corticosteroids for the therapy of hepatotoxicity.
  • Monitor liver operate assessments (ALT, AST and whole bilirubin) previous to the beginning of LUMAKRAS each 3 weeks for the primary 3 months of therapy, then as soon as a month or as clinically indicated, with extra frequent testing in sufferers who develop transaminase and/or bilirubin elevations.
  • Withhold, dose scale back or completely discontinue LUMAKRAS based mostly on severity of antagonistic response.

Interstitial lung illness (ILD)/pneumonitis 

  • LUMAKRAS may cause ILD/pneumonitis that may be deadly. Amongst 357 sufferers who obtained LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of sufferers, all circumstances have been Grade 3 or 4 at onset, and 1 case was deadly. LUMAKRAS was discontinued as a result of ILD/pneumonitis in 0.6% of sufferers.
  • Monitor sufferers for brand new or worsening pulmonary signs indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Instantly withhold LUMAKRAS in sufferers with suspected ILD/pneumonitis and completely discontinue LUMAKRAS if no different potential causes of ILD/pneumonitis are recognized.

Commonest antagonistic reactions 

  • The commonest antagonistic reactions occurring in ≥ 20% have been diarrhea, musculoskeletal ache, nausea, fatigue, hepatotoxicity and cough.

Drug interactions 

  • Advise sufferers to tell their healthcare supplier of all concomitant medicines, together with prescription medicines, over-the-counter medication, nutritional vitamins, dietary and natural merchandise.
  • Inform sufferers to keep away from proton pump inhibitors and H2 receptor antagonists whereas taking LUMAKRAS.
  • If coadministration with an acid-reducing agent can’t be prevented, inform sufferers to take LUMAKRAS 4 hours earlier than or 10 hours after a domestically performing antacid.

Please see LUMAKRAS full Prescribing Info.  


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