Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication LUMAKRAS is an inhibitor of the RAS GTPase family indicated for: KRAS G12C-mutated Locally Advanced or Metastatic 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 AMG 510, Lumakras, Lumykras, Lumakras (US), Lumykras (UK)
Sotorasib · 9 trials · 9 indications
PFS is defined as the time from randomization until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first. Progression will be based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, per Blinded Independent Central Review (BICR).
OS is defined as the time from randomization until death due to any cause.
PFS was defined as time from randomization until disease progression or death from any cause, whichever occurred first, for all participants. Progression was assessed using RECIST v1.1 per BICR.
Incidence and severity of TEAEs, clinically significant changes in vital signs, and clinical laboratory tests will be reported as TEAEs.
DLTs were defined as any of the following adverse events (AEs) where a relationship to sotorasib could not be ruled out. Hematological toxicity * febrile neutropenia * neutropenic infection * grade 4 neutropenia * grade ≥ 3 thrombocytopenia for \> 7 days * grade 3 thrombocytopenia with grade ≥ 2 bleeding * grade 4 thrombocytopenia * grade 4 anemia. Non-hematological toxicity * grade ≥ 4 vomiting or diarrhea * grade 3 diarrhea or grade 3 vomiting lasting more than 3 days despite optimal medical support * grade ≥ 3 nausea for 3 days or more despite optimal medical support * any other grade ≥ 3 adverse event.
An AE was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after first dose of study treatment. Treatment-related TEAEs were any TEAEs considered related to investigational product by the investigator. If relationship was missing, the event was assumed treatment-related. Clinically significant changes from the participant's baseline values in vital signs, 12-lead electrocardiograms, and clinical laboratory safety tests were reported as AEs.
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.
Treatment-emergent adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy dose comparison
Treatment-related adverse events will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
Grade ≥3 treatment-emergent adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
Serious adverse events will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
Adverse events of interest will be a primary outcome measure in the following group: \- Phase 2 monotherapy dose comparison
Vital signs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
Physical examinations will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1
ECGs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
Abnormal clinical laboratory values will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
DLTs will be a primary outcome measure for the following groups: * Phase 1 Dose Exploration Part 1 monotherapy * Phase 1 Dose Expansion Part 2 monotherapy * Phase 1 combination arm with sotorasib and anti PD-1/L1 * Phase 1 monotherapy treatment naïve advanced NSCLC
ORR will be a primary outcome measure in the following group: * Phase 1 monotherapy treatment naïve advanced NSCLC * Phase 2 monotherapy * Phase 2 monotherapy dose comparison
DOR will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
Disease control will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
Duration of SD will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
TTR will be a primary outcome measure in the following group: \- Phase 1 monotherapy treatment naïve advanced NSCLC
| Arm | Type | Description |
|---|---|---|
| Arm A: Sotorasib + Panitumumab + FOLFIRI | EXPERIMENTAL | Sotorasib will be taken daily (QD) as an oral tablet. Panitumumab and FOLFIRI will be received every 2 weeks (Q2W) via intravenous (IV) infusion. |
| Arm B: FOLFIRI with or Without Bevacizumab-awwb | ACTIVE_COMPARATOR | Participants will receive FOLFIRI Q2W with or without bevacizumab-awwb. |
| Sotorasib combined with carboplatin and pemetrexed | EXPERIMENTAL | Sotorasib administered in combination with carboplatin and pemetrexed. |
| Pembrolizumab combined with carboplatin and pemetrexed | ACTIVE_COMPARATOR | Pembrolizumab administered in combination with carboplatin and pemetrexed. |
| Arm A: Sotorasib 960 mg QD + panitumumab | EXPERIMENTAL | - |
| Arm B: Sotorasib 240 mg QD + panitumumab | EXPERIMENTAL | - |
| Arm C : Investigator's choice | ACTIVE_COMPARATOR | Participants will be administered trifluridine and tipiracil, or regorafenib |
| AMG 510 | EXPERIMENTAL | - |
| Docetaxel | ACTIVE_COMPARATOR | - |
| Arm A: Sotorasib | EXPERIMENTAL | Sotorasib will be administered once daily, orally in 28-day treatment cycles for up to approximately 18 months or until withdrawal of consent, lost to follow-up, or death, whichever occurs first. |
| Arm B: Sotorasib in Combination with Panitumumab | EXPERIMENTAL | Sotorasib will be administered once daily, orally, in combination with Panitumumab intravenous (IV) infusion every two weeks on Day 1 and Day 15 in 28-day treatment cycles. Treatment will continue for up to approximately 18 months or until withdrawal of consent, lost to follow-up, or death, whichever occurs first. |
| Normal Hepatic Function | EXPERIMENTAL | - |
| Moderate Hepatic Impairment | EXPERIMENTAL | - |
| Severe Hepatic Impairment | EXPERIMENTAL | - |
| Treatment Arm | EXPERIMENTAL | Subjects will be enrolled and will receive AMG 510 PO QD. |
| Sotorasib + trametinib + panitumumab | EXPERIMENTAL | Experimental: Sotorasib + trametinib + panitumumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors. |
| Sotorasib + RMC-4630 | EXPERIMENTAL | Experimental: Sotorasib + RMC-4630 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants, with KRAS p.G12C mutant advanced solid tumors. |
| Sotorasib + afatinib | EXPERIMENTAL | Experimental: Sotorasib + afatinib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer. |
| Sotorasib + panitumumab +/- chemotherapy | EXPERIMENTAL | Experimental: Sotorasib + panitumumab +/- chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors. |
| Sotorasib + atezolizumab | EXPERIMENTAL | Experimental: Sotorasib + atezolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer. |
| Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab | EXPERIMENTAL | Experimental: Sotorasib + carboplatin, pemetrexed, docetaxel, paclitaxel, pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer. |
| Sotorasib Monotherapy | EXPERIMENTAL | Experimental: Sotorasib only Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced non-small cell lung cancer with brain metastases. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced non-small cell lung cancer with brain metastases. |
| Sotorasib + palbociclib | EXPERIMENTAL | Experimental: Sotorasib + palbociclib Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor. |
| Sotorasib + pembrolizumab | EXPERIMENTAL | Experimental: Sotorasib + pembrolizumab Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant non small cell lung cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS P.G12C mutant non small cell lung cancer. |
| Sotorasib + MVASI® (bevacizumab-awwb)+ Chemotherapy | EXPERIMENTAL | Experimental: Sotorasib + MVASI® (bevacizumab-awwb)+ chemotherapy Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced colorectal cancer. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced colorectal cancer. |
| Sotorasib + TNO155 | EXPERIMENTAL | Experimental: Sotorasib + TNO155 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors. |
| Sotorasib + BI 1701963 | EXPERIMENTAL | Experimental: Sotorasib + BI 1701963 Dose Exploration and Dose Expansion * Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. * Upon completion of dose exploration part of the study the dose expansion cohort is for eligible participants with KRAS P.G12C mutant advanced non-small cell lung cancer and advanced colorectal cancer. |
| Sotorasib + AMG 404 | EXPERIMENTAL | Experimental: Sotorasib + AMG 404 Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C mutant advanced solid tumors. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumors |
| Sotorasib + everolimus | EXPERIMENTAL | Experimental: Sotorasib + everolimus Dose Exploration and Dose Expansion • Enrollment into the dose exploration cohort is for eligible participants with KRAS P.G12C advanced solid tumor. • Upon completing the dose exploration part of the study, dose expansion may proceed consisting of participants with KRAS p.G12C mutant advanced solid tumor. |
| Phase 1 Dose Exploration Part 1 monotherapy | EXPERIMENTAL | Cohorts with food effect and alternative dosing regimens Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort |
| Phase 1 Dose Expansion Part 2 monotherapy | EXPERIMENTAL | Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently |
| Phase 1 combination arm with sotorasib and anti PD-1/L1 | EXPERIMENTAL | Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1) |
| Phase 1 monotherapy treatment naive advanced NSCLC | EXPERIMENTAL | Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days. |
| Phase 2 monotherapy dose comparison | EXPERIMENTAL | Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy |
| Phase 1 Does escalation and Expansion monotherapy BID | EXPERIMENTAL | BID 2L+solid tumors (fed state) |
| Name | Type | Description |
|---|---|---|
| FOLFIRI Regimen | DRUG | Combination of irinotecan, leucovorin, and 5-fluorouracil given via IV infusion Q2W. |
| Sotorasib | DRUG | Immediate-release solid dosage form administered orally. |
| Panitumumab | DRUG | Administered via IV infusion Q2W. |
| Bevacizumab-awwb | DRUG | Administered via IV infusion Q2W. |
| Pembrolizumab | DRUG | Intravenous administration |
| Trifluridine and Tipiracil | DRUG | Trifluridine and Tipiracil will be administered orally |
| Regorafenib | DRUG | Regorafenib will be administered orally |
| AMG 510 | DRUG | 21 day cycles |
| Docetaxel | DRUG | 21 day cycles |
| Trametinib | DRUG | Trametinib administered orally as a tablet. |
| RMC-4630 | DRUG | RMC-4630 administered orally as a capsule. |
| Afatinib | DRUG | afatinib administered orally as a tablet. |
| Carboplatin, pemetrexed, docetaxel, paclitaxel | DRUG | Carboplatin, pemetrexed, docetaxel administered as an IV infusion. |
| Atezolizumab | DRUG | Atezolizumab administered as an IV injection. |
| Palbociclib | DRUG | Palbociclib administered orally as a tablet. |
| MVASI® (bevacizumab-awwb) | DRUG | MVASI® (bevacizumab-awwb) administered as an IV infusion. |
| TNO155 | DRUG | TNO155 administered orally as a capsule. |
| IV Chemotherapy (Regimen 1) | DRUG | Chemotherapy combination of leucovorin administered as an IV injection, 5-fluorouracil (5-FU) administered as IV bolus injection or IV continuous infusion (depending on dose), and irinotecan administered as IV injection. |
| IV Chemotherapy (Regimen 2) | DRUG | IV chemotherapy combination of leucovorin administered as an IV injection, 5-FU administered as IV bolus injection or IV continuous infusion (depending on dose), and oxaliplatin administered as IV injection. |
| BI 1701963 | DRUG | BI 1701963 administered orally |
| AMG 404 | DRUG | AMG 404 administered as an IV infusion. |
| Everolimus | DRUG | Everolimus administered orally. |
| Anti PD-1/L1 | DRUG | Administered as an intravenous (IV) infusion |
| Midazolam | DRUG | Administered as an oral hydrochloride (HCI) syrup |
Inclusion Criteria: * Pathologically documented metastatic colorectal adenocarcinoma with KRAS p.G12C mutation by a locally validated assay. * Central laboratory detection of KRAS p.G12C mutation. * Measurable metastatic disease per RECIST v1.1 criteria. * Eastern Cooperative Oncology Group (ECOG) ...
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Sotorasib is an oral small molecule KRAS inhibitor developed by Amgen Inc. (NASDAQ: AMGN) for cancers driven by the KRAS p.G12C mutation. It is being studied in advanced solid tumors, metastatic colorectal cancer, and KRAS p.G12C mutant advanced non-small cell lung cancer. It is an investigational therapy in clinical development.
Sotorasib is used in clinical trials to treat advanced solid tumors that carry the KRAS p.G12C mutation, including metastatic colorectal cancer and KRAS p.G12C mutant advanced non-small cell lung cancer. Treatment is biomarker-selected, meaning patients must test positive for the KRAS p.G12C mutation to be eligible for study enrollment.
Sotorasib targets KRAS, specifically the p.G12C mutant form of the protein, and acts as an inhibitor. By binding the KRAS p.G12C mutant, it is designed to block signaling that drives tumor growth in cancers harboring this mutation. It is a small molecule administered orally.
Sotorasib is developed by Amgen Inc., which trades on NASDAQ under the ticker AMGN. Amgen sponsors the clinical program evaluating sotorasib both as a single agent and in combination regimens, including pairings with panitumumab and platinum doublet chemotherapy, across multiple solid tumor indications.
Sotorasib is in clinical development and is investigational. Its trial program includes Phase 2 and Phase 3 studies, with a Phase 3 trial in metastatic colorectal cancer and a Phase 3 trial in nonsquamous non-small cell lung cancer currently recruiting, and a completed Phase 3 study in colorectal cancer.
Sotorasib trials include NCT07172919, a Phase 2 rollover study with or without panitumumab in KRAS p.G12C mutation; NCT06252649, a Phase 3 study in metastatic colorectal cancer; NCT05920356, the Phase 3 CodeBreaK 202 study in nonsquamous NSCLC; and NCT05198934, a completed Phase 3 colorectal cancer study.
Yes, Sotorasib is also known as AMG 510. AMG 510 is the earlier code name used for the same Amgen KRAS p.G12C inhibitor during its development. Readers searching for AMG 510 are looking at the same investigational compound as sotorasib.