dm+d

Unassigned

New Medicines

Metastatic, KRAS G12c mutated non-small cell lung cancer (NSCLC) - second-line therapy

Information

New molecular entity
Mirati
Mirati

Development and Regulatory status

None
Pre-registration (Filed)
Pre-registration (Filed)
May 22Mirati announce it has submitted an MAA to the EMA for adagrasib for the treatment of patients with non-small cell lung cancer (NSCLC) harboring the KRASG12C mutation who have received at least one prior systemic therapy. The MAA is supported by data from the registration enabling cohort of the Phase 2 KRYSTAL-1 study [7].
Feb 22Adagrasib filing accepted by FDA for review with Prescription Drug User Free Action (PDUFA) date of December 14, 2022. [6]
Jan 22Adagrasib is considered by analysts to have blockbuster potential [6].
Jan 22Mirati expects a greenlight Q2 22 with imminent plans to launch [5].
Dec 21Filed in US for second-line treatment for NSCLC [5].
Nov 21Mirati plan to file adagrasib as second-line treatment for NSCLC in the US Q4 2021 [3].
Jun 21FDA grants Breakthrough Therapy Designation [4].

Category

Highly selective and potent oral small molecule KRAS inhibitor
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 [1].
Metastatic, KRAS G12c mutated non-small cell lung cancer (NSCLC) - second-line therapy
Oral

Trial or other data

May 22Mirati announces cohort data from PI/II KRYSTAL-1 study. Data from 116 patients, the majority of whom had prior treatment with a PD-1/L1 inhibitor after chemotherapy, at 12.9 months after treatment in the trial, shows ORR was 43%, and the disease control rate was 80%. Median duration of response was 8.5 months while median progression free survival was 6.5 months. Lumakras, on the other hand, recorded a lower objective response rate in data released at last year ’s ASCO conference from a similar population of 124 patients who had previously received both platinum-based chemotherapy and immunotherapy. But the duration of response for Lumakras was more than two and a half months longer than adagrasib at 11.1 months. The disease control rate was the same at 80%. On overall survival, adagrasib recorded 12.6 months as of the Jan. 15 data cutoff vs. 12.5 months with Lumakras [9].
Feb 22PI/II KRYSTAL-1 study evaluate the safety, tolerability, drug levels, molecular effects, and clinical activity of MRTX849 (adagrasib) in patients with advanced solid tumours that have a KRAS G12C mutation is recruiting (NCT03785249). 740 adults will be recruited in the US and Puert0 Rico. Primary outcomes are safety, pharmacokinetics and objective response rate [8].
Nov 21PIII KRYSTAL-12 (NCT04685135) ongoing with aim to evaluate the efficacy of adagrasib versus docetaxel in patient who have been previously treated for metastatic NSCLE with a KRAS G12c mutation. The study aims to enrol 452 participants and with a primary completion date of December 2022. Primary outcome measures are overall survival and progression-free survival [2].

KRAS G12C mutated colorectal cancer, second-line therapy

Information

Licence extension / variation
Mirati
Mirati

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Highly selective and potent oral small molecule KRAS inhibitor
Bowel cancer is the 4th most common cancer in the UK, accounting for 11% of all new cancer cases in 2016-2018; most cases occur in the rectum [1]. Prevalence of KRAS G12C mutation is ~3-4% and is generally associated with poor prognosis [2].
KRAS G12C mutated colorectal cancer, second-line therapy
Oral