Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication KRAZATI is an inhibitor of the RAS GTPase family indicated for: Non-small cell lung cancer (NSCLC)* • As a single agent, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC, as determined by an FDA-approved test, who have received at least one prior systemic therapy. FDA label
Also known as MRTX849, Adagrasib dose of twice daily, BMS-986503, Krazati, KRAS G12C, Pembrolizumab, Pemrolizumab, KRAS G12C inhibitor
Adagrasib · 10 trials · 15 indications
Defined as time from randomization until disease progression or death from any cause, whichever occurs first.
Progression-free survival (PFS) is defined as the time from randomization to the date of progression or death due to any cause, whichever occurs first. 95% CI was obtained using Brookmeyer and Crowley method. Participants who are not observed to have progressed or died are censored at the date of last evaluable tumor assessment. Disease progression assessed as per RECISIST 1.1 was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
ORR evaluation of subjects treated with adagrasib 600 mg BID without regard to food versus 400 mg BID with food having NSCLC with KRAS G12C mutation (Study Population) will be completed per blinded independent central radiology (BICR) review. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from 1st dose of adagrasib until last dose of adagrasib.
Defined as the percent of patients documented to have a confirmed CR or PR
PFS is defined as time from first study treatment until disease progression or death from any cause, whichever occurs first.
Objective Response Rate (ORR) as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Progression Free Survival per RECIST 1.1 by Blinded Independent Central Review (BICR) and Overall Survival
Number of participants with treatment emergent adverse events
Plasma concentration
Number of patients with dose limiting toxicity
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
Number of participants with treatment related adverse events
Blood plasma concentration
Number of participants with treatment related adverse events
Blood plasma concentration
Objective response rate in accordance with Response Evaluation Criteria in Solid Tumors (RECIST)
| Arm | Type | Description |
|---|---|---|
| Adagrasib | EXPERIMENTAL | - |
| Placebo | PLACEBO_COMPARATOR | - |
| MRTX849 + Cetuximab | EXPERIMENTAL | - |
| mFOLFOX6 or FOLFIRI | ACTIVE_COMPARATOR | - |
| MRTX849 | EXPERIMENTAL | - |
| Docetaxel | ACTIVE_COMPARATOR | - |
| Arm A1 | EXPERIMENTAL | - |
| Arm A2 | EXPERIMENTAL | - |
| Arm B1 | EXPERIMENTAL | - |
| Arm B2 | EXPERIMENTAL | - |
| Arm B3 | EXPERIMENTAL | - |
| Arm B4 | EXPERIMENTAL | - |
| Arm C1 | EXPERIMENTAL | - |
| Arm C2 | EXPERIMENTAL | - |
| Arm C3 | EXPERIMENTAL | - |
| Arm C4 | EXPERIMENTAL | - |
| Adagrasib 600mg BID | EXPERIMENTAL | Adagrasib 600mg BID without regard to food |
| Adagrasib 400mg BID | EXPERIMENTAL | Adagrasib 400mg BID with food |
| Cohort A: PD-L1 TPS≥ 1% (Closed) | EXPERIMENTAL | Adagrasib 400 mg BID for 2 cycles followed by adagrasib 400 mg BID + pembrolizumab 200 mg every 3 weeks (Q3W) up to 35 cycles |
| Cohort C | EXPERIMENTAL | Adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W up to 31 cycles |
| Cohort E | EXPERIMENTAL | Adagrasib 400 mg BID + pembrolizumab 200 mg Q3W + pemetrexed 500 mg/m2 + cisplatin 75 mg/m2 Q3W OR carboplatin AUC 5 Q3W for 4 cycles, followed by adagrasib 400 mg BID + pemetrexed 500 mg/m2 Q3W + pembrolizumab 200 mg Q3W (up to 31 cycles) |
| Phase 2 Cohort 1a: PD-L1 TPS <1% | EXPERIMENTAL | Cohort 1a: Adagrasib twice daily (BID) in combination with pembrolizumab |
| Phase 2 Cohort 1b: PD-L1 TPS <1% | EXPERIMENTAL | Cohort 1b: Adagrasib BID monotherapy |
| Phase 2 Cohort 2: PD-L1 TPS ≥1% | EXPERIMENTAL | Cohort 2: Adagrasib BID in combination with pembrolizumab |
| Phase 3 Cohort 3 Investigational Arm | EXPERIMENTAL | Adagrasib BID in combination with pembrolizumab |
| Phase 3 Cohort 4 Comparator Arm | ACTIVE_COMPARATOR | Pembrolizumab |
| Dose Escalation | EXPERIMENTAL | Dose escalation of MRTX849 and palbociclib to determine maximum tolerated dose in combination. |
| Dose Expansion | EXPERIMENTAL | Expansion cohorts may be implemented to ensure sufficient safety experience, pharmacokinetic data and early evidence of clinical activity of MRTX in combination with palbociclib. |
| Phase 1 Dose Exploration | EXPERIMENTAL | Dose escalation of TNO155 to determine maximum tolerated dose of TNO155 in combination with MRTX849 |
| Phase 1b Expansion | EXPERIMENTAL | Expansion cohort to ensure sufficient safety experience, pharmacokinetic information, and early evidence of clinical activity of MRTX849 in combination with TNO155 to recommend Phase 2 regimens |
| Phase 2 | EXPERIMENTAL | Separate cohorts of patients stratified by histological diagnosis for evaluation of clinical activity to evaluate clinical activity of MRTX849 and TNO155 in combination |
| Pilot Phase 1b Combination with Pembrolizumab | EXPERIMENTAL | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with pembrolizumab in patients with NSCLC |
| Pilot Phase 1b Combination with Cetuximab | EXPERIMENTAL | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with CRC |
| Pilot Phase 1b Combination with Afatinib | EXPERIMENTAL | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with afatinib in patients with NSCLC |
| Phase 2 Combination with Cetuximab | EXPERIMENTAL | Phase 2 evaluation of the clinical activity of MRTX849 in combination with cetuximab in patients with CRC |
| Pilot Phase 1b Combination with Cetuximab in NSCLC | EXPERIMENTAL | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with NSCLC |
| Pilot Phase 1b Combination with Cetuximab in PDAC | EXPERIMENTAL | Phase 1 evaluation of the safety, tolerability, PK and clinical activity of MRTX849 in combination with cetuximab in patients with pancreatic adenocarcinoma (PDAC) |
| Name | Type | Description |
|---|---|---|
| Adagrasib | DRUG | Specified dose on specified days |
| Pembrolizumab | DRUG | Specified dose on specified days |
| Carboplatin | DRUG | Specified dose on specified days |
| Pemetrexed | DRUG | Specified dose on specified days |
| Placebo | DRUG | Specified dose on specified days |
| Cisplatin | DRUG | Specified dose on specified days |
| MRTX849 | DRUG | 28 Day Cycle |
| Cetuximab | BIOLOGICAL | 28 Day Cycle |
| mFOLFOX6 Regimen | DRUG | * Fluorouracil * Oxaliplatin * Folinic acid |
| FOLFIRI Regimen | DRUG | * Fluorouracil * Irinotecan * Folinic acid |
| Docetaxel | DRUG | 21 day cycles |
| Irinotecan | DRUG | Specified dose on specified days |
| Leucovorin | DRUG | Specified dose on specified days |
| Oxaliplatin | DRUG | Specified dose on specified days |
| Fluorouracil | DRUG | Specified dose on specified days |
| Adagrasib oral dose of 400 mg twice daily tablets | DRUG | oral dose of 400 mg twice daily tablets |
| Chemotherapy: Pemetrexed | COMBINATION_PRODUCT | IV infusion once every 3 weeks |
| Cisplatin/Carboplatin | COMBINATION_PRODUCT | IV infusion once every 3 weeks |
| Palbociclib | DRUG | CDK 4 and 6 inhibitor |
| TNO155 | DRUG | SHP2 Inhibitor |
| Afatinib | DRUG | Afatinib will be administered orally once a day in a continuous regimen |
Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of non-squamous NSCLC with evidence of KRAS G12C mutation via tumor sample and/or circulating tumor deoxyribonucleic acid (ctDNA). * Locally advanced or metastatic disease. * Measurable disease via computed tomography (CT) or...
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Adagrasib is an investigational oral small molecule being studied for advanced cancers, including advanced non-small cell lung cancer and advanced colorectal cancer. It is also being evaluated in advanced solid tumors and other carcinomas. The clinical program focuses on patients whose tumors carry specific mutations, and studies are ongoing in multiple countries.
Adagrasib targets KRAS, a signaling protein that is mutated in many cancers. It acts as a KRAS inhibitor, designed to bind the mutant protein and block the signals that drive tumor growth. The studies specifically enroll patients with KRAS G12C mutations, making it a biomarker-selected therapy.
Adagrasib is being developed by Bristol-Myers Squibb Company, which trades on the New York Stock Exchange under the ticker BMY. The company is running a clinical program that includes Phase 2 and Phase 3 trials in lung cancer and other solid tumors.
Adagrasib is in clinical development, with a Phase 2 program and a Phase 3 trial. It is investigational and has not been approved by the FDA for any indication. The Phase 3 KRYSTAL-4 trial is evaluating Adagrasib plus pembrolizumab plus chemotherapy in previously untreated non-squamous non-small cell lung cancer.
Adagrasib is being studied in several trials, including NCT07415031, a Phase 2 long-term treatment study for patients who participated in prior Adagrasib studies; NCT06875310 (KRYSTAL-4), a Phase 3 trial in previously untreated non-squamous NSCLC; NCT05853575 (KRYSTAL 21), a Phase 2 dosing regimen trial; and NCT05609578, a Phase 2 combination therapy trial in advanced NSCLC.
Yes, Adagrasib is also known as MRTX849. It is an oral tablet taken at a dose of 400 mg twice daily. The names MRTX849 and Adagrasib refer to the same investigational KRAS inhibitor developed by Bristol-Myers Squibb.