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Association details:
Evidence:
Evidence Level:
Sensitive: A1 - Approval
Title:

Mirati Therapeutics Receives Approval from the MHRA for KRAZATI (adagrasib) as a Targeted Treatment Option for Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation

Published date:
11/03/2023
Excerpt:
Mirati Therapeutics...announced the United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA) granted conditional marketing authorization approval for KRAZATI® (adagrasib) as a monotherapy indicated for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with KRASG12C mutation and have progressive disease after prior therapy with, or intolerance to, platinum-based chemotherapy and/or anti-PD-1/PD-L1 immunotherapy.
Evidence Level:
Sensitive: A1 - Approval
Source:
Published date:
12/12/2022
Excerpt:
KRAZATI is an inhibitor of the RAS GTPase family indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA approved test, who have received at least one prior systemic therapy.
Evidence Level:
Sensitive: A2 - Guideline
Source:
Title:

Therapy for Stage IV Non–Small-Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2023.1

Published date:
04/06/2023
Excerpt:
For patients with advanced NSCLC and a KRAS G12C mutation who have received prior systemic therapy with chemotherapy and anti–programmed death (ligand)-1 therapy, clinicians may offer treatment (monotherapy) with adagrasib…
DOI:
10.1200/JCO.23.00281
Evidence Level:
Sensitive: A2 - Guideline
New
Source:
Excerpt:
Non-Small Cell Lung Cancer….KRAS G12C Mutation...Subsequent therapy...Adagrasib
Evidence Level:
Sensitive: B - Late Trials
Title:

Mirati Therapeutics' Adagrasib Receives Breakthrough Therapy Designation from U.S. Food and Drug Administration for Patients with Advanced Non-Small Cell Lung Cancer Harboring the KRAS G12C Mutation

Published date:
06/24/2021
Excerpt:
Mirati Therapeutics, Inc...announced today that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to adagrasib for the potential treatment of patients with non-small cell lung cancer (NSCLC) who harbor the KRASG12C mutation following prior systemic therapy.
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Phase 2 Trial of Adagrasib Monotherapy and in Combination With Pembrolizumab and a Phase 3 Trial of Adagrasib in Combination in Patients With a KRAS G12C Mutation KRYSTAL-7

Excerpt:
...- Phase 2: Histologically confirmed diagnosis of unresectable or metastatic NSCLC with KRAS G12C mutation and any PD-L1 TPS...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Study of INCB099280 in Combination With Adagrasib in Adults With Advanced Solid Tumors Harboring a KRASG12C Mutation

Excerpt:
...- KRASG12C-mutated solid malignancy determined by a sponsor-approved assay using either tumor tissue or ctDNA....
Trial ID:
More C2 evidence
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Adagrasib in Patients With KRASG12C-mutant NSCLC Who Are Elderly or Have Poor Performance Status

Excerpt:
...KRASG12C-mutation by local testing (by tissue or ctDNA)....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A study of adagrasib for patients with KRASG12C-mutant non-small cell lung cancer (NSCLC), who are elderly or who are unwell because of their lung cancer. Un estudio de adagrasib para pacientes con cáncer de pulmón de células no pequeñas (CPCNP) con mutación KRASG12C, que son ancianos o que no se encuentran bien debido a su cáncer de pulmón.

Excerpt:
...- Histologically or cytologically confirmed stage IV NSCLC- KRASG12C-mutation by local testing (by tissue or ctDNA)- Prior treatment with at least one line of systemic therapy for NSCLC (e.g., platinum-based doublet chemotherapy and/or immune-checkpoint inhibition or both).- Life expectancy ≥12 weeks- Measurable disease according to RECIST v1.1- Age ≥18 years with ECOG PS 2 (cohort 1), or age ≥70 years with ECOG PS 0-1 (cohort 2)- Adequate haematological, renal and liver function- Negative pregnancy test for patients of childbearing potential- Ability to comply with the trial protocol, in the investigator's judgment.-Written informed consent for protocol treatment must be signed and dated by the patient and the investigator prior to any trial-related intervention, including the submission of mandatory biomaterial. ...
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation (KRYSTAL -19)

Excerpt:
...- Histologically confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Phase 1/2 Study of MRTX0902 in Solid Tumors With Mutations in the KRAS MAPK Pathway

Excerpt:
...MRTX0902 and adagrasib combination therapy: KRAS G12C mutation....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

A Study of BMS-986466 With Adagrasib With or Without Cetuximab in Participants With Kirsten Rat Sarcoma Virus Glycine 12 to Cysteine (KRAS G12C)-Mutant Solid Tumors

Excerpt:
...Individuals must have a documented KRAS G12C mutation status from NYS or FDA approved/cleared or CE marked test or, when such result is...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Phase 3 Study of MRTX849 (Adagrasib) vs Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation

Excerpt:
...- Histologically or cytologically confirmed diagnosis of NSCLC with KRAS G12C mutation....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Adagrasib in Combination With BI 1701963 in Patients With Cancer (KRYSTAL 14)

Excerpt:
...- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 1b must be either Non-Small Cell Lung Cancer or Colorectal Cancer)...
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Phase 2 Study of MRTX849 Plus Pembrolizumab in Patients with AdvancedNon-Small Cell Lung Cancer with KRAS G12C Mutation Sperimentazione di fase 2 su MRTX849 più pembrolizumab in pazienti con carcinoma polmonare non a piccole cellule in stadio avanzato con mutazione KRAS G12C

Excerpt:
...1.Histologically confirmed diagnosis of NSCLC (squamous or nonsquamous) with KRAS G12C mutation and 2. ...
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Combination Therapies With Adagrasib in Patients With Advanced NSCLC With KRAS G12C Mutation

Excerpt:
...Cohort A* (closed): Has an untreated and unresectable or metastatic NSCLC with histologically confirmed (squamous or nonsquamous) KRASG12C mutation and histologically confirmed PD-L1 TPS ≥1%....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Trial of Two Adagrasib Dosing Regimens in NSCLC With KRAS G12C Mutation (KRYSTAL 21)

Excerpt:
...- Have advanced NSCLC or metastatic NSCLC (NSCLC that started in the lungs and then spread to other parts of the body) with the KRAS G12C mutation....
Trial ID:
Evidence Level:
Sensitive: C2 – Inclusion Criteria
New
Title:

Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2)

Excerpt:
...- Histologically confirmed diagnosis of a solid tumor malignancy with KRAS G12C mutation (phase 2 must be either Non-Small Cell Lung Cancer or Colorectal Cancer)...
Trial ID:
Less C2 evidence
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Mirati Therapeutics Receives Positive Opinion from CHMP for KRAZATI (adagrasib) as a Targeted Treatment Option for Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with a KRASG12C Mutation Following a Re-Examination Procedure

Published date:
11/10/2023
Excerpt:
Mirati Therapeutics...announced that following a re-examination procedure, the Company has received a positive opinion from the European Medicine Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) on KRAZATI® (adagrasib) as a targeted treatment option for adult patients with KRASG12C -mutated advanced non-small cell lung cancer (NSCLC) and disease progression after at least one prior systemic therapy....KRYSTAL-1 is an open-label Phase 1/2 multiple-expansion cohort trial evaluating adagrasib as monotherapy and in combination with other anti-cancer therapies in patients with advanced solid tumors harboring the KRASG12C mutation.
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Intracranial Efficacy of Adagrasib in Patients From the KRYSTAL-1 Trial With KRASG12C–Mutated Non–Small-Cell Lung Cancer Who Have Untreated CNS Metastases

Published date:
06/16/2023
Excerpt:
We evaluated adagrasib in patients with KRASG12C–mutated NSCLC and untreated CNS metastases from the KRYSTAL-1 trial...Adagrasib demonstrated an IC objective response rate of 42%, disease control rate of 90%, progression-free survival of 5.4 months, and median overall survival of 11.4 months.
DOI:
10.1200/JCO.23.00046
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

8MO - Adagrasib (MRTX849) in Patients With Advanced/Metastatic KRASG12C-Mutated Non-Small Cell Lung Cancer (NSCLC): Preliminary Analysis of Mutation Allele Frequency

Published date:
03/23/2023
Excerpt:
Pts with previously treated KRASG12C-mutated NSCLC received ada 600 mg orally BID….ORR by blinded independent central review (BICR) was 42.9%, disease control rate 79.5%, median PFS 6.5 months (95% CI 4.7–8.4) and, with longer follow-up (cutoff 15 Jan 2022), median OS 12.6 months (95% CI 9.2–19.2)....Ada showed promising efficacy and manageable tolerability in previously treated pts with KRASG12C-mutated NSCLC.
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Adagrasib in Non–Small-Cell Lung Cancer Harboring a KRASG12C Mutation

Published date:
07/14/2022
Excerpt:
In a registrational phase 2 cohort, we evaluated adagrasib (600 mg orally twice daily) in patients with KRASG12C -mutated non-small-cell lung cancer (NSCLC)….Of 112 patients with measurable disease at baseline, 48 (42.9%) had a confirmed objective response. The median duration of response was 8.5 months (95% confidence interval [CI], 6.2 to 13.8), and the median progression-free survival was 6.5 months (95% CI, 4.7 to 8.4). As of January 15, 2022 (median follow-up, 15.6 months), the median overall survival was 12.6 months (95% CI, 9.2 to 19.2)....In patients with previously treated KRASG12C -mutated NSCLC, adagrasib showed clinical efficacy without new safety signals.
DOI:
10.1056/NEJMoa2204619
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Adagrasib Response Remains Strong in NSCLC

Published date:
06/06/2022
Excerpt:
In the phase II KRYSTAL-1 trial, the KRASG12C inhibitor adagrasib yielded an overall response rate of 43% and a disease control rate of 80% in patients with previously treated KRASG12C-mutant non-small cell lung cancer. After a median follow up of 12.9 months, overall survival was 11.7 months. The drug also shrank brain metastases in 33% of patients who had them.
DOI:
10.1158/2159-8290.CD-NB2022-0042
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

Activity of Adagrasib (MRTX849) in Brain Metastases: Preclinical Models and Clinical Data From Patients With KRASG12C-Mutant Non-Small Cell Lung Cancer

Published date:
04/11/2022
Excerpt:
Patients with KRAS-mutant NSCLC demonstrated high propensity to develop BM ({greater than or equal to}40%). Adagrasib penetrated into CSF and demonstrated tumor regression and extended survival....In 2 patients with NSCLC and untreated BM, CSF concentrations of adagrasib measured above the target cellular IC50. Both patients demonstrated corresponding BM regression, supporting potential clinical activity of adagrasib in the brain....These data support further development of adagrasib in patients with KRASG12C-mutant NSCLC with untreated BM.
DOI:
10.1158/1078-0432.CCR-22-0383
Evidence Level:
Sensitive: C3 – Early Trials
Title:

First-in-Human Phase I/IB Dose-Finding Study of Adagrasib (MRTX849) in Patients With Advanced KRASG12C Solid Tumors (KRYSTAL-1)

Published date:
02/15/2022
Excerpt:
Patients with advanced KRASG12C-mutant solid tumors were treated with adagrasib...Of these 20 patients, the primary diagnosis was KRASG12C-mutant non–small-cell lung cancer (NSCLC; n = 16), KRASG12C-mutant CRC (n = 2), and KRASG12C-mutant mucinous appendiceal carcinoma (n = 2), respectively. After a median follow-up of 19.6 months, eight of 15 patients (53.3%; 95% CI, 26.6 to 78.7) with RECIST-evaluable KRASG12C-mutant non-small-cell lung cancer treated at 600 mg twice a day achieved a confirmed partial response.
DOI:
10.1200/JCO.21.02752 Journal of Clinical Oncology
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Source:
Title:

99O_PR - KRYSTAL-1: Activity and Preliminary Pharmacodynamic (PD) Analysis of Adagrasib (MRTX849) in Patients (Pts) With Advanced Non–Small- Cell Lung Cancer (NSCLC) Harboring KRASG12C Mutation

Published date:
03/17/2021
Excerpt:
79 pts with pretreated NSCLC were treated with adagrasib 600 mg BID (phase I/Ib and phase II)….Among the 51 pts evaluable for clinical activity, 45% (23/51) had a partial response (PR) and 26 pts had stable disease (SD)….Adagrasib is tolerable and has demonstrated clinical activity in pts with previously treated KRASG12C-mutant NSCLC.
Trial ID:
Evidence Level:
Sensitive: C3 – Early Trials
Title:

ES28.02 - Clinical Data for KRAS G12C Inhibitors

Published date:
01/12/2021
Excerpt:
In a phase 1/2 multi-expansion cohort trial (KRYSTAL-1), adagrasib was evaluated in patients with advanced solid tumors harboring KRAS G12C mutations....Pooled data on responses to adagrasib showed an ORR of 43% in the 14 evaluable patients treated with the single agent in the phase 1/1b, which included PRs in 43% and SD in 57%, for a DCR of 100%.
Evidence Level:
Sensitive: C3 – Early Trials
Title:

KRYSTAL-1: Activity and Safety of Adagrasib (MRTX849) in Advanced/Metastatic Non–Small-Cell Lung Cancer (NSCLC) Harboring KRAS G12C Mutation

Published date:
10/25/2020
Excerpt:
Among the 51 patients evaluable for clinical activity (14 from Phase 1/1b; 37 from Phase 2), 45% of patients had an objective response (23/51 which includes 5 patients who had an unconfirmed partial response and remain on treatment). Disease control rate was 96% (49/51) of patients....Adagrasib is tolerable and demonstrates durable clinical activity in patients with previously treated KRAS G12C-mutant NSCLC.
Evidence Level:
Sensitive: C3 – Early Trials
New
Source:
Title:

MRTX849 Shows Clinical Activity in Patients With KRAS G12C-mutant Solid Cancers

Excerpt:
...phase I trial 17 patients with solid tumors bearing KRAS G12C mutations….The initial MRTX849 dose of 150 mg once daily was escalated to doses up to 1,200 mg daily….Of the 12 evaluable patients, six had metastatic NSCLC and three had partial responses...treatment with MRTX849 was well tolerated...
Evidence Level:
Sensitive: D – Preclinical
Title:

Evaluation of KRASG12C inhibitor responses in novel murine KRASG12C lung cancer cell line models

Published date:
02/08/2023
Excerpt:
In contrast to the LLC 46 NRAS KO model, orthotopic lung tumors established with the mKRC.1 cell line exhibited a significant single-agent anti-tumor response to MRTX-849...
DOI:
https://doi.org/10.3389/fonc.2023.1094123
Evidence Level:
Sensitive: D – Preclinical
Source:
Title:

1841 / 13 - MRTX849 inhibits P-gp and demonstrates CNS exposure in mouse models and cancer patients and demonstrates antitumor activity in intracranial mouse models of lung cancer brain metastasis

Published date:
03/09/2022
Excerpt:
...treatment with MRTX849 resulted in potent tumor regression and significant survival extension in another intracranial KRAS G12C model of NSCLC…